ACT on Alzheimer’s



ACT on Alzheimer’sAlzheimer’s Disease CurriculumModule VII: Disease Diagnosis GUIDELINES AND RESTRICTIONS ON USE OF DEMENTIA CURRICULUM MODULESThis curriculum was created for faculty across multiple disciplines to use in existing coursework and/or to develop as a stand-alone course in dementia. Because not all module topics will be used within all disciplines, each of the ten modules can be used alone or in combination with other modules. Users may reproduce, combine, and/or customize any module text and accompanying slides to meet their course needs. Use restriction: The ACT on Alzheimer's?-developed dementia curriculum cannot be sold in its original form or in a modified/adapted form.NOTE: Recognizing that not all modules will be used with all potential audiences, there is some duplication across the modules to ensure that key information is fully represented (e.g., the screening module appears in total within the diagnosis module because the diagnosis module will not be used for all audiences). ? 2016AcknowledgementWe gratefully acknowledge the funding organizations that made this curriculum development possible: the Alzheimer’s Association MN/ND and the Minnesota Area Geriatric Education Center (MAGEC), which is housed in the University of MN School of Public Health and is funded by the Health Resources and Services Administration (HRSA).We specifically acknowledge the principal drafters of one or more curriculum modules, including Mike Rosenbloom, MD; Olivia Mastry, MPH, JD; Gregg Colburn, MBA; and the Alzheimer’s Association.In addition, we would like to thank the following contributors and peer review team:Michelle Barclay, MATerry Barclay, PhDMarsha Berry, MA, CAEdErin Hussey, DPT, MS, NCSSue Field, DNP, RN, CNEJulie Fields, PhD, LPJane Foote EdD, MSN, RNHelen Kivnik, PhDKenndy Lewis, MSRiley McCarten, MDTeresa McCarthy, MD, MSLynne Morishita, GNP, MSNBecky Olson-Kellogg, PT, DPT, GCSJim Pacala, MD, MSPatricia Schaber, PhD, OTR/LJohn SelstadEricka Tung, MD, MPHJean Wyman, PhD., RN, GNP-BC, FAAN, FGSAThis project is/was supported by funds from the Bureau of Health Professions (BHPr), Health Resources and Services Administration (HRSA), Department of Health and Human Services (DHHS) under Grant Number UB4HP19196 to the Minnesota Area Geriatric Education Center (MAGEC) for $2,192,192 (7/1/2010—6/30/2015). This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by the BHPr, HRSA, DHHS or the U.S. Government.Minnesota Area Geriatric Education Center (MAGEC)Grant #UB4HP19196Director: Robert L. Kane, MDAssociate Director: Patricia A. Schommer, MAOverview of Alzheimer’s Disease CurriculumThis is a module within the Dementia Curriculum developed by ACT on Alzheimer’s. ACT on Alzheimer’s is a statewide, volunteer-driven collaboration seeking large-scale social change and community capacity-building to transform Minnesota’s response to Alzheimer’s disease. An overarching focus is health care practice change to ensure quality dementia care for all. All of the dementia curriculum modules can be found online at .Module I:Disease DescriptionModule II:DemographicsModule III:Societal ImpactModule IV:Effective Interactions Module V:Cognitive Assessment and the Value of Early DetectionModule VI:ScreeningModule VII:Disease Diagnosis Module VIII:Dementia as an Organizing Principle of CareModule IX:Quality InterventionsModule X:Caregiver SupportModule XI:Alzheimer’s Disease ResearchModule XII:GlossaryACT on Alzheimer's has developed a number of practice tools and resources to assist providers in their work with patients and clients who have memory concerns and to support their care partners. Among these tools are a protocol practice tool for cognitive impairment, a decision support tool for dementia care, a protocol practice tool for mid- to late-stage dementia, care coordination practice tools, and tips and action steps to share with a person diagnosed with Alzheimer's. These best practice tools incorporate the expertise of multiple community stakeholders, including clinical and community-based service providers:Clinical Provider Practice ToolElectronic Medical Record (EMR) Decision Support ToolManaging Dementia Across the ContinuumCare Coordination Practice ToolCommunity Based Service Provider Practice ToolAfter A DiagnosisWhile the recommended practices in these tools are not location-specific, many of the resources referenced are specific to Minnesota.? The resource sections can be adapted to reflect resources specific to your geographic area.?To access ACT practice tools and resources, as well as video tutorials on screening, assessment, diagnosis, and care coordination, visit: VII: Learning ObjectivesUpon completion of this module the student should:Identify screenings and examinations used to diagnose and assess current state of cognitive functioning. Gain an understanding of the benefits of early diagnosis.Understand the steps involved in identifying and diagnosing Alzheimer’s and related dementias.Module VIIDisease DiagnosisCase Study:Mr. Johnson, a 71 year-old man with a history of diabetes who currently lives alone, is brought into the clinic by his son, Dave. Mr. Johnson does not believe he has any significant memory problems, yet Dave describes 2.5 years of progressive memory deficits characterized by increasing late fees while paying bills and difficulty maintaining the household. Over the past three months, Dave has received repeated phone calls from his father in which he complains repeatedly about losing items around the household. At one point, he wondered whether somebody was stealing his keys and reading glasses. Originally, Dave suspected that his father was fixated on this topic but, over time, it became clear that he had forgotten about the original conversations. His cognitive review of systems is remarkable for forgetting appointments and becoming lost while driving in familiar neighborhoods. Dave mentions that he is worried about his dad’s driving as well. He denied any specific symptoms for depression.The past medical history includes diabetes and hypertension. He was previously on a more complicated medication regimen aiming for “tighter” blood sugar control. He is now taking metformin, which is taken two times a day, lisinopril, and a baby aspirin, which can be taken once a day. He will occasionally take Tylenol PM (with diphenhydramine) at night for sleep. The primary provider is hoping that simplifying the medication regimen will make it easier for Mr. Johnson to follow instructions accurately. Mr. Johnson is a retired janitor with a high school education. No active smoking or drinking. There is a family history of Alzheimer’s disease in his father who developed symptoms at age 81. Neurological exam was non focal. Neuropsychological screening showed a MoCA=21 (losing points for cube copy, 1/5 words after 5 minutes [could not recognize when given a list], orientation to date, clock draw). Laboratory studies showed normal complete blood count, electrolytes, LFTs, glucose, thyroid stimulating hormone, and B12 levels. A referral was made for neuropsychological testing: Mr. Johnson showed severe deficits in learning and memory, moderate deficits in visuospatial function, and mild executive impairments. The Geriatric Depression Scale score was 2 and within normal limits. Brain MRI was positive for bilateral hippocampal and parietal atrophy, but no evidence for stroke or focal lesions.Mr. Johnson was diagnosed by his primary provider with probable Alzheimer’s disease. Dave inquired about any interventions that can possibly slow or treat the disease process. It is clear that Dave is distressed about his father’s new diagnosis. He has many questions about his father’s safety and how he can proactively take steps to ensure his dad’s well-being.Dementia is a disease process that leads to a functional decline through the compromise of cognitive, behavioral, and/or motor function from a previously normal baseline. Dementia can be due to several etiologies with the most common being Alzheimer’s disease (AD) followed by Lewy body dementia (LBD), fronotemporal dementia (FTD), and vascular dementia (VD). AD is the underlying cause of dementia in 60-80% of cases with the prevalence expected to triple by 2050 (Alzheimer’s Facts and Figures, 2012). Although this condition is relatively common, the medical establishment has been mostly unsuccessful in identifying the disease with 50% of diagnoses missed by primary care providers (Kerwin, 2009). [For more on the distinction between “dementia” and Alzheimer’s disease, please refer to ] Detecting dementia through patient and family observations can be particularly challenging due to the slow, progressive nature of Alzheimer’s symptoms, and consequently symptoms may go unnoticed by those within close contact to the cognitively impaired individual. To complicate matters, individuals with dementia often lack self-awareness of cognitive decline, a common characteristic of dementia, which can prevent them from reporting and raising awareness of their memory issues.A diagnosis of Alzheimer’s disease is most commonly made by a specialist, such as a neurologist, geriatrician, or geriatric psychiatrist. The process of diagnosing AD consists of gathering subjective and objective information, like pieces of a puzzle, to formulate a cohesive diagnosis. A Minnesota statewide collaboration of Alzheimer’s experts and stakeholders, called ACT on Alzheimer’s, has developed a provider checklist consisting of four “steps.” The provider first obtains a history and performs a neurological examination with neuropsychological screening (STEP 1). Next, further diagnostics are gathered including laboratory studies and neuroimaging to address potentially reversible causes of dementia. When indicated, this step may also include formal neuropsychological testing (STEP 2). The provider then reviews the subjective and objective data to establish a diagnosis while considering the range of disease process that may result in dementia (STEP 3), eventually organizing a formal meeting with patient and family to discuss diagnosis, prognosis, and treatment plan (STEP 4). The Clinical Provider Practice Tool was developed by ACT on Alzheimer’s.STEP 1: History and Exam A. Obtaining the Medical History:Compared to most neurological diseases, AD is a particularly challenging disease to characterize based on medical history. The presenting individual may be unreliable as a historian or narrator based on either cognitive impairment and/or limited insight into his/her condition. Thus, the healthcare provider should always ensure that a supplemental history be obtained from a family member, friend, or caregiver to ensure accuracy. For more information regarding the challenges of diagnosis of AD, please refer to major historical elements to cover in a medical history include:symptom quality, symptom onset and course, and impact on social/occupational function. i. Symptom quality: The quality of the first symptom and onset may offer helpful clues into the underlying disease process. The early stages of AD usually involve episodic memory problems that include forgetting conversations, bill payment, or work deadlines. In conditions such as frontotemporal dementia, the initial symptoms may consist of behavioral changes such as disinhibition or apathy. Individuals with depression usually present with behavioral health complaints of depressed mood, insomnia, loss of appetite, psychomotor retardation, and occasionally suicidal ideation. Depression is usually a contributing factor rather than a primary cause of cognitive decline. The Alzheimer’s Association has identified 10 common symptoms that may indicate cognitive impairment consistent with AD. These include:Memory loss that disrupts daily life, especially forgetting recently learned information, forgetting important dates or events, and asking for the same information over and over again.Challenges in planning or solving problems, including changes in the ability to develop and follow a plan or work with numbers.Difficulty completing familiar task at home, at work or at leisure.Confusion with time or place, including losing track of dates, seasons, and the passage of time.Trouble understanding visual images and spatial relationship. New problems with words in speaking or writing.Misplacing things and losing the ability to retrace steps.Decreased or poor judgment.Withdrawal from work or social activities.Changes in mood and personality.See 10 Early Signs of Alzheimer’s Disease. Alzheimer’s Association. may further observe individuals experiencing difficulty with missing appointments, forgetting medications, making repeated phone calls to the provider, unusual sleeping habits, inappropriate clothing or lack of personal hygiene, and weight changes. These signs are all red flags for dementia.ii. Symptom onset and course: The onset and course of cognitive symptoms is helpful for suggesting a particular disease process and potential staging. The clinician is probably dealing with a relatively early process in a patient with three months of symptoms compared to an individual with three years of memory loss. In addition, an individual experiencing symptoms consistent with AD for a more prolonged period may be more likely to fall in the category of the moderate-severe disease stages. Sometimes, patients may complain of decades of symptoms, which would be inconsistent with AD and suggestive of either baseline impairment or mood disorder. Disease course is important as most neurodegenerative disease processes present with slow decline over months-years. An individual with AD may typically present with episodic memory complaints over a period of 2-3 years. However, there are processes such as Creutzfeldt-Jakob disease (CJD) that present as rapidly progressive dementia with cognitive, behavioral, and motor decline over weeks-months. The healthcare provider should always remember to distinguish dementia from delirium, an acute condition characterized by waxing and waning mental status over days-weeks usually occurring in a hospital setting. It should also be noted that the course of the symptoms may not be obvious during the initial evaluation, and therefore, longitudinal follow-up is recommended.Impact on social/occupational function: By definition, dementia is a condition that results in disruption of social and occupational function, so the provider should be certain to address the impact of the memory and cognitive dysfunction. Function can be further subdivided into the Instrumental Activities of Daily Living (IADLs) and Activities of Daily Living (ADLs). The IADLs refer to more complex activities such as medication administration, grocery shopping, meal preparation, telephone use, driving/transportation, finances, housekeeping, and laundry, whereas the ADLs consist of more basic tasks such as bathing, dressing, toileting, transferring, grooming, and feeding. In AD, patients initially experience compromise of the IADLs in the early stages with later progression to the ADLs. This information can be obtained either from history or using a standardized scale such as the functional assessment questionnaire (FAQ) Establishing the degree of functional impairment is important in distinguishing dementia from mild cognitive impairment (MCI). Mild cognitive impairment is used to describe a condition when a patient and/or their family, friends, or caregivers report a loss of cognitive or behavioral function; in this case, cognitive testing demonstrates abnormal performance, but the decline is not sufficient to cause functional impairment. The most common form of MCI involves memory loss and is called amnestic MCI. In many cases, patients with MCI will progress to dementia over time. The rate of progression to dementia is about 10-15% per year, so that in about five years approximately 50% of MCI patients will progress to dementia (Petersen, 2005).B. Cognitive Review of SystemsAlthough AD is the most common cause of dementia, the provider should also be aware of other associated neurodegenerative processes such as Lewy body dementia, vascular dementia, and frontotemporal dementia that may result in functional decline but which typically have different cognitive/behavioral profiles. Therefore, it is recommended that a complete cognitive review of systems be performed to assess deficits involving memory, executive function, language, and visuospatial function. The definitions of these areas of cognitive functioning are listed below:Memory: There are multiple types of memory including episodic memory, working memory, semantic memory, and procedural memory (Budson, 2005). In the case of Alzheimer’s disease, episodic memory, a type of memory specific for remembering events and experiences, is impaired. This type of memory localizes to the hippocampus and limbic regions (Budson, 2005).Executive Function: A general term pertaining to a set of cognitive processes that include planning, working memory, complex attention, problem solving, verbal reasoning, inhibition, mental flexibility, multi-tasking, and initiation and monitoring of action. The localization of this function is within the prefrontal networks. Essentially, executive functions are complex functions that allow one to engage in effective and efficient goal-directed behavior. Language: Language can be understood in terms of an ability to express and comprehend speech. Other abilities that fall under language include reading, writing, naming, and repetition. Most language disorders present with deficits in expressive speech, comprehension, repetition, and/or naming. Language function localizes to the dominant left hemisphere with anterior frontal structures (e.g., Broca’s area) involved in speech expression and posterior temporal structures participating in comprehension (e.g., Wernicke’s area). Visuospatial Function: Refers to an ability to appreciate spatial locations and relationships. Individuals with dementia often demonstrate compromise of this system when trying to park or pull their car into a garage. Visuospatial function localizes to the right parietal and higher visual cortex (occipito-parieto-temporal cortex). The degree of compromise involving a specific system may provide clues to the underlying process. Whereas AD is a condition that traditionally compromises memory, a review of systems may indicate predominant involvement of another system such as language, at which point an alternative disease process may be considered. It should also be noted that as AD progresses, the condition may impact all four of the cognitive modalities. Finally, it is recommended that a neuropsychiatric and behavior review addressing issues such as depression, anxiety, hallucinations, and sleep be performed. Table 1: A Cognitive Review of SystemsMemory QuestionsDifficulty remembering recent eventsDifficulty remembering remote eventsProblems with misplacing objectsRepetitive questioningMissing appointmentsProblems remembering to take medicationsProblems remembering to pay billsExecutive Function QuestionsDifficulty with planning or organizationDifficulty with multi-taskingProblems with poor judgment/making bad decisionsDifficulty with poor concentration or shortened attention spanDifficulty problem solvingMental rigidity/inflexibilityImpulsivityRepetitive behaviorsRestlessnessFluctuations in cognitionLanguage QuestionsDifficulty finding wordsProblems with slurred speechImpaired comprehensionNonfluent speechImpoverished speechImpaired word comprehensionImpaired reading, writing, or spellingIncreased speech outputDecreased speech outputMutismVisuospatial Function QuestionsAny recent motor vehicle accidentsProblems with becoming lost in familiar environmentsTrouble seeing things properlyDifficulty recognizing facesImpaired object perceptionDifficulty driving or parking a carBehavioral QuestionsChanges in personality or behaviorApathy or decreased motivationEvidence of depressionEvidence of anxietyProblems with agitation or irritabilityDelusions or hallucinationsChanges in weight or appetiteProblems with sleeping or daytime somnolenceEvidence of REM sleep behavioral disorderC. Neurological Examination:Individuals with a suspected diagnosis of AD should undergo a formal neurological evaluation to assess mental status, rule out focal findings that may be seen in stroke, and assess for Parkinson’s. A neurological examination consists of a mental status, cranial nerve evaluation, motor and coordination exam, sensory evaluation, testing of reflexes, and gait assessment. The majority of individuals presenting with AD have a generally non-focal neurological exam. Below are characteristic exam findings that may distinguish AD from other associated dementias. Alzheimer’s disease:AD is characterized by short-term memory deficits (e.g., trouble recalling lists of words, remembering recent events, or problems with calculations or reconstructing a 2-dimensional figure shown previously from memory). Individuals struggle to recall life events occurring during the previous month, week, or even day. They often have difficulty remembering current events and may have trouble describing events of national significance, such as the destruction of the Twin Towers on 9/11/01. Usually, there are no focal findings on cranial nerve, motor, coordination, sensory, reflex, and gait assessment.For more information about AD, please refer to the following video clip: dementia:Individuals may present with focal exam findings including aphasia, homonymous hemianopsia, hemiparesis, hemisensory loss, apraxia, and visuospatial neglect. The most common mental status findings include frontal pattern of memory loss with impaired retrieval but intact recognition/encoding (Knopman, 2007). To learn more about vascular dementia, please refer to the following short clip: body dementia: Individuals have impaired arousability (problems with tests of alertness) and difficulty copying figures such as the intersecting pentagon. Neurological exam reveals parkinsonism (hypophonia, hypomimia, bradykinesia, tremor, cogwheel rigidity, slow shuffling gait). For more information on Lewy body dementia, please refer to the following: dementia spectrum:Individuals may demonstrate behavioral disinhibition and impulsivity on observation. Individuals with the primary progressive aphasia variant will demonstrate chronic progressive expressive language deficits. Exam may show problems performing anti-saccadic task or Luria 3 step. Motor exam may reveal frontal release signs (e.g., grasp, palmomentalis, rooting). All of these clinical signs localize to the frontal lobes. Please refer to the following video clip regarding frontotemporal Dementia: pressure hydrocephalus (NPH):In addition to executive and attention deficits noted on cognitive testing, NPH individuals should show a magnetic gait (i.e., inability to lift feet or legs, as if feet are stuck to the floor) that improves following large volume spinal tap. Please refer to the following clip for some more information about NPH: () D. Early Cognitive Assessment and Cognitive Screening:All individuals with memory and cognitive complaints should undergo a cognitive screening test. The purpose of the test is to provide a quick assessment of the individual’s cognitive ability. In contrast to formal neuropsychological testing, cognitive screening does not confirm a diagnosis, but is a gross measure that suggests whether a subject’s performance may be normal versus abnormal. There are a number of steps one can take to more effectively administer a cognitive screening test. First, a relaxed demeanor is important. It will hopefully put the patient at ease. Second, the test should be clearly explained to the patient. Emphasizing that certain questions will be more difficult, while others will be easier, is important. The individual should be encouraged to simply do his/her best. The examiner should continue to support the patient throughout the test, especially if s/he is struggling. Actions to Avoid During Cognitive ScreeningWhile it is important to foster a nurturing environment for the individual, one should not do anything to reduce the validity of the test results. The following is a list of actions an examiner should avoid:Do not allow the individual to give up prematurely.Do not deviate from standardized instructions.Do not offer multiple choice answers.Do not bias score by coaching.Do not be generous in scoring; score ranges already incorporate normal errors.List of Screening MeasuresThere are a number of cognitive assessment measures available to providers. Each test has its own benefits and drawbacks and the provider needs to determine which test will best serve the interests of his/her patients and the practice. Mini-CogThe Mini-Cog is a 5 point cognitive screen that incorporates three-word verbal recall (3 points) and a clock draw (2 points; 1 point for numbers and 1 point for clock hands; N.B. length of hands do not impact the score) (Borson, et al., 2000). The subject is first given three words to register followed by a clock draw. After the drawing of the clock (which can be created either from scratch or by filling in a pre-drawn circle), the subject is asked to recall the three words. Studies have shown that the word choice may increase the sensitivity of the screen with the most sensitive word combination being “leader, season, table” (McCarten, et al., 2011). In addition, the clock draw is particularly more sensitive when the examiner uses phrasing that is more abstract by instructing the patient to set the time to “10 past 11” as opposed to 11:10. The test was originally validated with a <3 cutoff indicating failure (Borson et al 2000), but recent studies have utilized scores <4 as indicating failing with scores ≥ 4 indicating passing (McCarten, 2011). The <4 cutoff is thought to increase the test’s sensitivity for dementia. Advantages of the test include the ability to cover a broad range of cognitive modalities including executive function, memory, and visuospatial function during a short administration time ranging from 1.5-3 minutes, making this test ideal for the rushed primary care setting (McCarten, et al., 2011). Furthermore, the performance on this test is not affected by education or language (Borson, et al., 2000). Recent studies have compared the Mini-Cog with the Mini Mental Status Exam (MMSE), which often requires seven or more minutes to administer, and have demonstrated similar sensitivity and specificity (MC vs MMSE: 76% vs. 79% sensitivity and 89% vs. 88% specificity) (Borson, et al., 2003). On the downside, the Mini-Cog is not considered to be as sensitive to mild cognitive impairment (MCI) or early dementia as more elaborate cognitive assessment tools, such as the Montreal Cognitive Assessment (MoCA). Partly due to the Mini-Cog’s ease of training and administration, several studies have evaluated the tool as a dementia cognitive assessment test within elderly populations free of cognitive disorders. Borson and colleagues administered the test to 524 subjects aged ≥65 in the primary care setting (Borson, et al., 2007). The investigators found that there was an 18% failure rate in combined primary care/geriatric clinic populations and that the test did not disrupt clinic flow. Interestingly, only 17% of providers took appropriate action for patients failing the test. McCarten and colleagues administered the Mini-Cog in 8,342 patients aged ≥70 in the setting of a VA hospital. It was found that the screen was well-accepted by older veterans and detected a 25.8% failure rate among the asymptomatic population (McCarten, et al., 2011). Currently, several Minnesota-based hospital systems such as HealthPartners and the Minneapolis VA are examining the benefits of integrating the Mini-Cog into the annual wellness visit for the geriatric population. Mini-Cog Administration and Scoring tutorial videos: Mini-Mental State Exam (MMSE) Mini Mental State Examination (MMSE) is one of the most commonly used cognitive assessment tools for dementia developed by Folstein in 1975 (Folstein, et al., 1975). The test is a 30 point scale consisting of questions addressing orientation, memory, visuospatial construction, and language. Scores ≥24 are considered normal (although recently dementia specialists have increased the cutoff score to 26). The test can usually be administered within a seven-minute time period. Traditionally, most dementia centers have been using the MMSE as a screen in patients with memory loss, and the test is often incorporated as a cognitive marker within clinical trials. One of the primary limitations of the MMSE is that the test has a low “ceiling,” and it is not uncommon for patients with cognitive disorders to score within the normal range. The screen was developed prior to the concept of mild cognitive impairment. Consequently, the test has an 18% sensitivity for MCI and a 78% sensitivity for dementia (Ismail, et al., 2010). In addition, the screen is heavily weighted toward language function and, therefore, may over-exaggerate disability in patients with primary language disorders. The MMSE also does a poor job of addressing executive function and patients with frontal deficits may score normally. Finally, the MMSE is copyrighted which constrains free usage of the tool.St. Louis University Mental Status Exam (SLUMS) Saint Louis University Mental Status Exam (SLUMS) was developed at Saint Louis University and was one of the first cognitive assessment tests to address mild cognitive disorders in addition to dementia (Tariq, et al., 2006). Performance outcome is divided into normal, mild neurocognitive disorder (based on Diagnostic and Statistic Manual-IV criteria), and dementia, and the screen adjusts the normal scores based on education. The test uses a 30-point scale similar to the MMSE, but it requires more time to administer compared to the MMSE (approximately 10 minutes). The test is superior to the MMSE in terms of addressing executive function and includes questions related to orientation, calculation, word generation, working memory, and visuospatial construction. The benefits of SLUMS include tasks addressing higher-level executive functions, as well as increased sensitivity for cognitive disorders compared to the MMSE. The test has a 92% sensitivity for MCI, 100% sensitivity for dementia, and 81% specificity for dementia. The screen is available free online which increases its usability.Drawbacks to the SLUMS include the complexity of the screen and increased time of administration. Furthermore, the test has less name recognition compared to the MMSE. SLUMS Administration and Scoring tutorial videos: Montreal Cognitive Assessment (MoCA) The Montreal Cognitive Assessment (MoCA) is a 30-point scale that was developed at the Montreal Neurological Institute (Nasreddine, et al., 2005) and is one of the most sensitive and specific cognitive screens available. The screen builds upon prior tests by providing tasks related to executive function in addition to language, visuospatial function, and memory. Studies suggest that individuals with ≤12 years of education have lower average scores on the test, so an additional point is given to this population during final scoring.The sensitivity of the test for MCI is 90% and 100% sensitivity for dementia (Nasreddine, et al., 2005). The specificity is 87% for dementia (Nasreddine, et al., 2005). Studies have shown that the MoCA is more sensitive, but less specific than the MMSE (Larner, 2012). Thus, the MoCA is a sufficient screen to capture patients in the earlier stages of MCI. In contrast to the MMSE, the MoCA includes tasks that are sensitive in detecting impairments in executive function and can distinguish word retrieval (found in frontal dysfunction) from recognition deficits (found in AD and disorders of medial temporal function). Other advantages include the fact that the test is free online and available in over 35 languages. The major drawback with the MoCA is that the test requires 12-15 minutes to administer and requires more intensive training for healthcare providers and therefore may be considered impractical in certain clinical environments. This particular screen would be ideal in a neurology specialty care environment. In addition, a population-based sample of ethnically diverse subjects showed that 66% of individuals fell below the suggested cutoff of 26, thus indicating the need to take into account demographic factors when interpreting test scores (Rossetti, et al., 2011). As a result of the screen’s ability to incorporate executive function, the MoCA has been studied to detect cognitive impairment and dementia in non-AD conditions impacting cognition including vascular cognitive impairment and dementia (Dong, et al., 2012), Parkinson’s disease (Dalrymple-Alford, et al., 2012), and obstructive sleep apnea (Chen, et al., 2011). MoCA Administration and Scoring tutorial videos: Kokmen Test of Mental StatusThe Kokmen is a mental status cognitive assessment test that was developed at the Mayo Clinic (Kokmen, et al., 1987). The screen consists of 38 points and has questions relating to orientation, attention, learning, calculation, abstraction, semantic memory, construction, and recall. Scores ≥36 are considered normal, 30-35 consistent with MCI, and ≤29 indicative of dementia. The test requires more time than the MMSE to administer, but has greater sensitivity for detecting cognitive impairment with a greater sensitivity for MCI, largely due to including a longer word list for recall, copying of a three-dimensional cube, and testing of working memory. The test is distinct from the other screens in that it uses a 38-point scale.Table 1: Comparison of Cognitive Screening TestsCognitive assessment TestAdministration TimeScale (pts.)MCI SensitivityDementiaSensitivityDementia SpecificityMiniCog1-3 min5 NA76%89%MMSE7 min3018%78%88-100%SLUMS10 min3092%100%81%MoCA12 min3090%100%87%E. Proceeding to Neuropsychological TestingThe most sensitive cognitive screens for MCI are the MoCA and SLUMS, but administration time may limit their utility within certain primary care clinics. In such situations, the Mini-Cog should be used as a bare minimum for purposes of initial screening. The decision to proceed with formal neuropsychological testing should be based on the history as well as performance on cognitive screening. Not all individuals require formal neuropsychological testing as such assessments have less diagnostic value in individuals with severely low scores on initial screening. Formal neuropsychological evaluation is recommended for individuals scoring in the following ranges on screening: MoCA 19-27; SLUMS 18-27; MMSE 18-28. However, it should be noted that between 8-10% of individuals will score within normal limits on the MoCA and SLUMS, and therefore, formal neuropsychological testing is still recommended in highly functioning individuals with persistent memory complaints. There may be other exceptions to these guidelines for ordering formal cognitive assessments, and ultimately, this decision will be based on individual provider discretion.STEP 2: Diagnostic EvaluationFollowing the history, examination, and cognitive screening, the healthcare provider should obtain objective studies to rule out reversible causes of dementia as well as confirm the absence of structural lesions on neuroimaging. Depending on the obtained history and individual’s performance on cognitive screening studies, this step may also consist of formal neuropsychological testing. A. Laboratory StudiesThe purpose of obtaining laboratory studies is to rule out reversible causes of dementia such as electrolyte imbalances, hypothyroidism, and B12 deficiency. Approximately 9% of dementias are potentially reversible (Clarefield, 2003). According to the recommendations from the American Academy of Neurology (AAN), all individuals presenting with memory and cognitive complaints should undergo evaluation of routine lab tests (CBC, lytes, BUN, Cr, Ca, LFTs, glucose) and dementia screening labs (TSH, B12) Depending on the individual’s history, it may be worthwhile checking for tertiary syphilis (RPR or MHA-TP), HIV (HIV-antibody), and lead (urine heavy metals). Our experience has shown that for the majority of individuals presenting with progressive memory loss, low B12 or abnormal thyroid function is usually a contributor rather than the primary cause of the cognitive disorder.B. NeuroimagingThe AAN recommends neuroimaging in all individuals undergoing a dementia evaluation. This imaging may involve either a head computerized tomography (CT) or a brain magnetic resonance imaging (MRI) study. The major purpose of neuroimaging involves ruling out a structural lesion that may result in dementia such as acute ischemic stroke, brain tumor, or hemorrhage. A brain MRI is a longer, more costly study but provides greater resolution of brain structures compared to a head CT. The AAN does not recommend one imaging modality over another. However, studies have shown correlations between hippocampal MRI volumes and episodic memory performance in individuals with AD (Cahn, 1998). Some behavioral neurologists prefer MRI due to the ability to examine for atrophy affecting structures commonly affected by AD such as the hippocampi and precuneus (refer to figure 1). Within the primary care setting, a brain MRI should be reserved for individuals with early onset dementia, a concerning history for focal lesions (e.g. stroke or cancer), atypical dementia symptoms, and/or focal findings on exam. If an individual has already had a CT or MRI in the past few months or in the setting of their current symptoms, then another CT or MRI is not needed.(Please see Appendix A. for more information on research criteria and Alzheimer-specific biomarkers.)Figure 1C. Neuropsychological TestingNeuropsychology is the study of how the brain is functioning and how this relates to cognition and behavior. Neuropsychologists are specialized professionals with training in neuroanatomy, neurophysiology, and brain-behavior relationships. They use operationalized, standardized, and well-characterized tests to answer questions regarding the presence or absence of cognitive impairment relative to an individual’s age and level of education, localization/lateralization of deficits in the brain, potential etiology of cognitive dysfunction, diagnostic classification (e.g., MCI vs dementia, AD vs vascular dementia), staging of dementia, and need for particular supportive interventions (e.g., driving retirement, supervision of medication administration, safety precautions, etc.). Whereas MRI examines brain structure, the neuropsychological evaluation focuses on brain function.Neuropsychological testing can help determine whether memory changes are normal age-related changes or if they reflect an organic neurological disorder. In addition, the evaluation can differentiate between dementia diagnoses, such as AD, LBD, FTD, and other conditions such as stroke, mood and psychiatric disorders, and substance abuse. In a way, the neuropsychological evaluation can be seen as an extension of the neurological exam. As mentioned previously, general guidelines for using neuropsychological testing should be based on history and the following performance ranges on cognitive screening; MoCA 19-27; SLUMS 18-27; MMSE 18-28.The neuropsychologist utilizes a testing battery to address the same cognitive modalities mentioned earlier in the cognitive review of systems: Learning/Memory, Executive Function, Attention, Language, Processing Speed, Visuospatial Function, and Mood/Personality. The goal is to examine both cortical (frontal, temporal, parietal) and subcortical integrity. Furthermore, testing can estimate baseline/premorbid cognitive abilities that then serve as a benchmark against which to compare performance observed in specific cognitive domains. Data is interpreted by statistical conversion of scores using well-validated normative data banks of healthy individuals across age and education spectrums. Neuropsychologists analyze data based on level of function (e.g., normal vs impaired), pattern recognition (e.g., amnestic vs forgetful, psychogenic vs organic), and localization (e.g., focal vs diffuse, medial temporal vs frontal/dysexecutive). Testing is tailored to each individual and may last anywhere from 1-4 hours. Each measure is generally fairly brief; lasting only a few minutes, and the exam is dynamic in nature meaning that many tests are discontinued at the point at which sufficient information is obtained. The process is engaging, mentally stimulating, and is designed to support the individual. Despite its length, the vast majority of individuals have no difficulty completing the exam in the allotted time frame. For a general description of the neuropsychological testing experience, please refer to: consists of encoding (which requires attention and registration of information), storage, consolidation (organization of information), and retrieval (recall and recognition of information). The most common ways to assess verbal learning and memory is by administering word list or story memory tasks. Common verbal list learning tasks include the California Verbal Learning Test-Second Edition (CVLT-II) (Delis, 2000) and the Hopkins Verbal Learning Test-Revised (HVLT-R) (Benedict, 1998). The most common story memory test is the Logical Memory subtest of the Wechsler Memory Scale-Fourth Edition (WMS-IV) (Wechsler, 2009). The examiner typically reads the list or story material repeatedly over successive trials to measure acquisition along a learning curve. In the case of a word list, the information could be read as many as 4-5 times. Individuals are then asked to spontaneously recall as much material as possible immediately after presentation and following a longer delay (generally 10-60 minutes). Many times, a recognition test follows in which individuals are given words or storylines one at a time and asked to differentiate previously presented material from distracters. Individuals who have intact recognition, but impaired recall, are said to have a retrieval deficit. Deficits in retrieval may be seen in a variety of conditions and are suggestive of a frontal-subcortical pattern of memory loss. Individuals who are unable to recall or recognize information have retrieval and recognition deficits. Deficits in recognition localize to the medial temporal lobe and suggest an Alzheimer’s process. Like verbal memory, visual memory is assessed using similar paradigms to analyze encoding, retrieval, and recognition deficits. Geometric designs or visual pictures that vary in complexity are shown to individuals. Common visual memory tasks include the Brief Visuospatial Memory Test-Revised (BVMT-R) (Benedict, 1996) and the Visual Recognition subtest of the Wechsler Memory Scale-Fourth Edition (WMS-IV) (Wechsler, 2009). Executive FunctionExecutive function is an umbrella term encapsulating a range of higher level functions that include planning, organizing, selective and complex attention, problem solving, reasoning, self-inhibition/monitoring, abstract thought, and mental flexibility. Some neuropsychologists may list attention under a separate category; however, the prefrontal cortices are largely responsible for all of these functions. Observations of frontal dysfunction on testing include perseveration, disinhibition, poor insight, concrete thinking, problems shifting attention, and poor organization. The Stroop test () is a common measure of executive function and is helpful in assessing processing speed and ability to inhibit over-learned responses. Individuals are presented with a page of words (“red”, “green”, and “blue”) printed in non-corresponding colors (e.g., the word “red” printed in blue ink) and asked to name the color of each word as quickly as possible. Proper performance on the measure requires the suppression of an overlearned task (reading words) in favor of a novel one (naming colors) and is therefore a sensitive measure of frontal lobe functions. The Trail Making Test, Part B is another test of executive functioning (), which requires the individual to connect dots in ascending order by alternating between numbers and letters. The test measures processing speed, visual scanning, multi-tasking, working memory, the ability to incorporate and adhere to rules, and self-monitor performance.LanguageNeuropsychologists make initial qualitative assessments of language function by close observation of fluency, comprehension, word-finding, prosody (rhythm of speech), and content during conversational speech. Formal testing consists of measures such as the Boston Naming Test (BNT) where subjects are asked to spontaneously name pictures of objects within a 20 second time frame (Kaplan, 1983). The items chosen for the test are both high frequency (e.g., broom) and low frequency (e.g., pyramid), which increases the sensitivity of the measure. Semantic and phonemic paraphasic errors are recorded in addition to naming accuracy. Other language tests include verbal fluency measures which require individuals to say as many words as possible in a 60 second time period beginning with a specific letter (e.g.. “F,” “A,” or “S”) or within a specific category (e.g., groceries or animals). Normally, subjects are more adept at generating words within a category (semantic fluency), compared to words beginning with a specific letter (phonemic fluency). Individuals with AD demonstrate a paradoxical shift such that phonemic fluency is relatively preserved compared to semantic fluency.Visuospatial FunctionVisuospatial function is indirectly assessed by inquiring about driving, navigation and facial recognition. Tests such as the Visual Object Spatial Perception task (VOSP) requires that subjects match the location of a dot to a number. Another common task is the copy of a complex figure such as the Rey Osterreith (refer to figure 2). Copy performance on this measure is analyzed based upon the individual’s ability to construct pieces of the figure in appropriate proportions, in correct orientation, and in reasonable spatial positioning relative to other pieces. Alternative figure copy tests use overlapping pentagons or 3-dimensional depictions of cubes and other figures. Judgment of line orientation tasks represent yet another way of measuring visuospatial functions.Figure 2:Mood/BehaviorClinical observation is particularly helpful in addressing mood disorders and behavioral health issues among individuals. Behaviors such as disinhibition, apathy, impulsivity, irritability, blunted or expansive affect, and inappropriate social responses may occur during the course of an interview and can be suggestive of frontal dysfunction. In addition, depressed mood and anxiety may be noted either through conversation or non-verbal cues. Depression and anxiety are common co-morbid conditions associated with various dementias, both as situational reactions to functional decline and as neuropsychiatric manifestations of the underlying organic neurodegenerative process. There are a number of recommended scales to quantify mood and behavioral symptoms in the context of a memory work-up, including the Neuropsychiatric Inventory (NPI) (Cummings, 1994), the Geriatric Depression Scale (GDS) (Yesavage, 1983) , and the Patient Health Questionnaire-9 (PHQ9)b (Spitzer, 1999).STEP 3: Establish a DiagnosisA. DiagnosisThe diagnosis of neurodegenerative disease requires the healthcare provider to integrate elements from the clinical history, neurological exam, cognitive screening, laboratory studies, neuropsychological testing, and neuroimaging to establish a final diagnosis. As a general rule, AD represents 60-80% of cases and, therefore, represents the most common diagnosis. However, the provider should be aware of associated disorders that may present in addition to AD (refer to table 2). Any individual presenting with atypical symptoms of parkinsonism, aphasia, or predominant behavioral symptoms should be referred to a neurology specialist. B. Barriers to DiagnosisAs mentioned previously, providers successfully diagnose AD only fifty percent of the time. There are individual-driven and provider-driven challenges that can impede dementia diagnosis. On the provider side, the following is a list of factors that can be a barrier for broader diagnosis of dementia:Insufficient training and knowledgeBelief that there are no effective treatmentsTime constraintsInsufficient reimbursementDisclosure discomfortFear of individual or family reactionBelief that specialists are more appropriate to make diagnosisAssociation of dementia with primarily the geriatric populationThe “fear of individual or family reaction” is one of the most commonly encountered provider-related barriers to early AD diagnosis. However, studies have shown that symptoms of stress and depression do not generally worsen significantly after disclosure of an AD diagnosis when compared to prediagnosis levels. In fact, markers of mood often show improvement for both the affected individuals and their family members once a specific diagnosis is in place to account for symptoms and guide treatment (Carpenter, 2008). From the individual perspective, there are additional barriers that contribute to diagnostic challenges. A few of those factors include:Lack of knowledge about dementia and/or the value of early detectionBelief that nothing can be donePerceived lack of services, resourcesTime constraintsFear, stigmaReluctance to self-advocateCommunication barriersCognitive impairment can result from a variety of potential causes in addition to the conditions listed above. Below is a list of potential disease etiologies that may result in memory loss with common diagnoses.Vascular: Ischemic or hemorrhagic stroke, reversible posterior leukoencephalopathy syndrome (RPLS), hypoxic injury after cardiac arrestInfectious: Herpes simplex virus (HSV) encephalitis, Human Immunodeficiency Virus (HIV) Dementia, NeurosyphilisToxic: Alcoholism, medication overdose or misuse, lead exposureAutoimmune: Systemic lupus erythematosus, central nervous system vasculitis, paraneoplastic disease, Hashimoto’s Encephalitis, NMDA-antibody encephalitisMetabolic: B12 deficiency, Wernicke-Korsakoff Syndrome (thiamine deficiency), electrolyte imbalance, hyper- or hypo-glycemia, obstructive sleep apnea (related to hypercapnia), hepatic encephalopathyNeoplastic: Brain tumor (e.g., CNS lymphoma, glioblastoma multiforme)Traumatic: Traumatic brain injury, chronic traumatic encephalopathyEndocrine: HypothyroidismEpisodic: Seizure disorder, migraine, transient global amnesia Neurodegenerative: Huntington’s disease (HD), progressive supranuclear palsy, corticobasal syndrome, spinocerebellar atrophy, multiple system atrophyFinally, the provider frequently must distinguish between a dementing illness and a delirium. A delirium frequently occurs in the setting of a toxic-metabolic disturbance and is characterized by transient, fluctuating disturbances in consciousness. The history, exam, and neuropsychological testing can all be helpful in distinguishing a primary memory disorder from delirium. STEP 4: Arrange a Family MeetingFollowing a dementia diagnosis, the provider should conduct a family meeting. The purpose of the meeting is to communicate the diagnosis to the family and discuss potential interventions as well as suggestions for disease management. It is critical that the meeting include family care partners to assist in not only information gathering, but also to help the individual effect a plan moving forward. Ideally, feedback should be delivered in a multidisciplinary manner with all healthcare providers present including the physician, social worker, and neuropsychologist. However, few clinics have such resources and, at the minimum, the physician should deliver the information relating to diagnosis, prognosis, treatment (both pharmacological and non-pharmacological), and community resources. A provider intervention checklist has been developed to provide a list of topics to discuss at the family meeting. and their families may also refer to the Alzheimer’s Association or the Senior Linkage Line for additional help and resources.The following tutorial video offers a demonstration of delivering a diagnosis to a patient: Traditionally, some healthcare providers have questioned the impact of early AD diagnosis. In addition to initiation of treatment, the educational component that is delivered through the family meeting significantly impacts quality of life. Studies have consistently shown the benefits of providing a wide variety of services and interventions, including:Appropriate use of available treatment options, both pharmacological and non-pharmacological;Effective management of coexisting conditions;Coordination of care among physicians, other health care professionals, and lay caregivers;Referral to community-based resources and services, including adult day and respite; andParticipation in activities, therapies and support groups, and services that enhance quality of life and care and can help address behavioral challenges associated with dementia (Callahan, 2006), (Mittelman, 2006), and (Wolfs, 2009). Once a diagnosis is made, providers should follow an intervention protocol. ACT on Alzheimer’s developed a comprehensive intervention checklist to guide providers and to ensure that all aspects of treatment have been addressed and as a useful companion to this module. ACT on Alzheimer’s Tools: In addition to the provider practice tools, The Care Coordination Practice Tool supports the coordination of care after a diagnosis. The After a Diagnosis Tool offers Action steps and tips medical and provider professionals can share with individuals and their family when a diagnosis of Alzheimer's or dementia is made. The Community Based Service Provider Practice Tool supports clients with memory concerns and their care partners. Community based service providers are critical in providing quality care to clients with dementia and their care partners.Early identification of the disease not only helps from a care management perspective, but it also helps the individual and primary caregivers to become more dementia competent and prepare for the significant changes that are to come. Failure to identify the disease places individuals and families at a distinct disadvantage as they manage care for their loved one. The benefits of early identification include:Rule out other causes of cognitive impairmentStart treatment early to maximize benefitBetter manage co-existing conditionsUnderstand symptoms and how to manage themMake decisions and plan for the futureBuild a support systemLower anxietyAvoid crisis driven careParticipate in clinical trials or other research(See Appendix A. regarding information on emerging research criteria and Alzheimer-specific biomarkers as a means for early diagnosis.)Module VII: Questions for ReviewMrs. Norton is a 78-year-old woman who is brought to your office by her daughter. Her daughter has noted that her mother is more forgetful than usual. She specifically cites that her mother repeats the same questions and stories. There was also one occasion when she forgot to go to a luncheon she was scheduled to attend. The patient denies any difficulty with managing her finances, or setting up her medications (and her daughter confirms that she can still do these tasks). Other than her mental status examination, the remainder of Mrs. Norton’s physical examination is normal. Her Short Test of Mental Status Examination (STME) is 29/38 (losing 2 points on orientation, 3 points on calculation, 1 point on construction, and 3 points on delayed recall). Which of the following laboratory studies is NOT indicated?Thyroid stimulating hormoneVitamin B12Complete blood countMRI of the brain CSF examination for total protein and glucoseMr. S. is an 82-year-old man who is brought into your office with recurrent visions of small animals and insects in his room at night. These visions are sometimes stressful to the patient and often confusing. His family notes that he is very forgetful and struggles to keep his house in order. He has become more withdrawn from loved ones and wants to spend most of his time at home by himself. He has fallen a number of times when transferring out of the shower, but he has never lost consciousness. He has a history of cognitive impairment that has not been fully worked up or treated. In the office, his Mini-Mental Status Examination is 22 out of 30. On physical examination, he has a difficult time rising to a standing position. His gait is slow and hesitant. Which of the following is the most likely diagnosis?Subdural hematoma from recurrent fallsDementia associated with cerebrovascular diseaseFrontotemporal dementiaAlzheimer’s diseaseDementia with Lewy bodiesWhich of the following statements is true?20-40% of dementia cases are due to Alzheimer’s disease40-50% of dementia cases are due to Alzheimer’s disease60-80% of dementia cases are due to Alzheimer’s diseaseFormal neuropsychological testing is required in order to make the diagnosis of Alzheimer’s diseaseDementia related to cerebrovascular disease is the second most common cause of dementia. Which of the following tests is most sensitive for detecting Mild Cognitive Impairment?Mini-CogSaint Louis University Mental Status Examination (SLUMS)Montreal Cognitive Assessment (MoCA)3 item recallWhich of the following statements is true?Early identification of dementia is not helpful as there are no evidence-based interventions available to provide to patients with early dementia.Early identification results in increased anxiety for patients and their families.Early identification is helpful, because pharmacologic treatment of patients with Mild Cognitive Impairment can prevent the development of dementia.Early identification is helpful and aides to prevent crisis driven care.Which of the following tasks is an example of the executive functioning?Word comprehensionRemembering remote historical eventsProblem solvingRecognizing facesVisual spatial manipulationWhich of the following is true about the role of imaging in the care of the patient with dementia?The American Academy of Neurology recommends against MRI imaging in the workup of dementia.A CT scan of the brain can rule out a structural lesion such as an acute stroke or brain tumor.Annual MRI of the brain is recommended to longitudinally follow hippocampal volume.CT imaging is the preferred modality to examine for atrophy of the hippocampi.Mr. Brown is a 62-year-old man who was diagnosed with dementia six months ago. Initially he struggled with mild short-term memory loss, but his wife brings him to the office today with new symptomatology. She notes that he has made sexually inappropriate remarks to his daughter-in-law and demonstrates decreased empathy for family members. His memory has been stable, according to his wife, but she has noticed a major change in his personality. Last week, he was asked to leave his favorite restaurant because of his inappropriate comments toward the server. Two months ago, he had an event where he was attempting to touch strangers during a church service. Mr. Brown’s clinical presentation is most consistent with which of the following conditions?Dementia associated with cerebrovascular diseaseFrontotemporal dementiaAlzheimer’s diseaseDementia with Lewy bodiesCreutzfeldt-Jakob diseaseWhich of the following studies is most helpful in the differentiation between different dementia subtypes (e.g. Alzheimer’s disease, Lewy body, frontotemporal dementia)Non-contrast CT scanMRI of the brain with gadoliniumNeuropsychological evaluationCBC with differentialSLUMs testReferencesAlladi, S., Xuereb, J., Bak, T., Nestor, P., Knibb, J., Patterson, K. & Hodges, J.R., (2007). Focal cortical presentations of Alzheimer's Disease. Brain, 130:10, 2636-2645.Benedict, R. H. B., Schretlen, D., Groninger, L. & Brandt, J. (1998). The Hopkins Verbal Learning Test-Revised: Normative data and analysis of interform and test-retest reliability. The Clinical Neuropsychologist, 12, 43–55.Benedict, R. H. B., Schretlen, D., Groninger, L., Dobraski, M. & Shritz, B. (1996). Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and Validity. Psychological Assessment, 8, 145–153. Borson, S., Scanlan, J., Brush, M., Vitaliano, P. & Dokmak, A. (2000).The mini-cog: Acognitive ‘vital signs’ measure for dementia screening in multi-lingual elderly. International Journal of Geriatric Psychiatry, 15(11):1021-1027.Borson, S., Scanlan, J.M., Chen, P. & Ganguli, M. (2003). The Mini-Cog as a screening for dementia: Validation in a population-based sample. Journal of the American Geriatric Society, 51(10):1451-1454.Borson, S., Scanlan, J., Hummel, J., Gibbs, K., Lessig, M. & Zuhr, E. (2007). Implementing routine cognitive screening of older adults in primary care: Process and impact on physician behavior. Journal of Geriatric International Medicine, 22(6):811-817.Braak, H., Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathology, 82(4):239.Cahn, D.A., Sullivan, E.V., Shear, P.K., Marsh, L., Fama, R., Lim, K.O., Yesavage, J.A., Tinklenberg, J.R. & Pfefferbaum, A. (1998). Structural MRI correlates of recognition memory in Alzheimer's disease. Journal of International Neuropsychology Society, 4(2):106-114.Carpenter, B.D., Xiong, C. & Porensky, E.K. (2008). Reaction to a dementia diagnosis in individuals with Alzheimer’s disease and mild cognitive impairment. Journal of American Geriatric Society, 56(3):405-412.Chen, R., Xiong, K.P., Huang, J.Y., Lian, Y.X., Jin, F., Li, Z.H., Zhao, M.Y. & Liu, C.F. (2011). Neurocognitive impairment in Chinese patients with obstructive sleep apnea hypopnea syndrome. Respirology, 16(5):842-848.Callahan, C.M., Boustani, M.A. & Unverzagt, F.W., (2006). Effectiveness of collaborative care for older adults with Alzheimer disease in primary care: A randomized controlled trial. JAMA, 295(18):2148-2157.Clarfield, A.M. (2003). The decreasing prevalence of reversible dementias: An updated meta-analysis. Arch International Medicine, 163(18):2219-2229.Cummings, J.L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D.A. & Gornbein, J. (1994).? The Neuropsychiatric? Inventory: comprehensive assessment of psychopathology in dementia.?Neurology, 44: 2308-2314.Dalrymple-Alford, J.C., MacAskill, M.R., Nakas, C.T., Livingston, L., Graham, C., Crucian, G.P., Melzer, T.R., Kirwan, J., Keenan, R., Wells, S., Porter, R.J., Watts, R., Anderson, T.J. (2010). The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology, 75(19):1717-1725.Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (2000).California Verbal Learning Test— (Second Edition). San Antonio, TX: The Psychological Corporation.Dong, Y., Venketasubramanian, N., Chan, B.P., Sharma, V.K., Slavin, M.J., Collinson, S.L., Sachdev, P., Chan, Y.H. & Chen, C.L. (2012). Brief screening tests during acute admission in patients with mild stroke are predictive of vascular cognitive impairment 3-6 months after stroke. Journal of Neurology, Neurosurgery and Psychiatry., 83(6):580-585. Folstein, M.F., Folstein, S.E. & McHugh, P.R. (1075). Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research. 12(3):189-198.Ismail, Z., Rajji, T.K. & Shulman, K.I. (2010). Brief cognitive screening instruments: an update. International Journal of Geriatric Psychiatry, 25(2):111-120.Jack, C.R. Jr, Vemuri, P., Wiste, H.J., Weigand, S.D., Aisen, P.S., Trojanowski, J.Q., Shaw, L.M., Bernstein, M.A., Petersen, R.C., Weiner & M.W., Knopman, D.S. (2011). Alzheimer's Disease Neuroimaging Initiative. Evidence for ordering of Alzheimer disease biomarkers .Arch Neurology, 68(12):1526-1535.Kaplan, E., Goodglass, H. & Weintraub, S. (1983). Boston Naming Test. Philadelphia: Lea & Febiger. Kerwin, D.R. (2009). How to prevent a delayed Alzheimer’s diagnosis: Physicians fail to detect mild-to-moderate dementia more than half the time. Here’s when to screen and which tools to use. The Journal of Family Practice, 58(1), 9-15. Kokmen, E., Naessens, J.M., Offord, K.P. (1987) A short test of mental status: description and preliminary results. Mayo Clinic Proceddings.62(4):281-288.Knopman, D.S. (2007). Cerebrovascular disease and dementia. The British Journal of Radiology, 80(2) S121-127.Larner, A.J. (2012). Screening utility of the Montreal Cognitive Assessment (MoCA): in place of--or as well as--the MMSE? International Psychogeriatric. 24(3):391-6. McCarten, J.R., Anderson. P., Kuskowski, M.A., McPherson, S.E. & Borson, S. (2011). Screening for cognitive impairment in an elderly veteran population: acceptability and results using different versions of the Mini-Cog. Journal of the American Geriatric Society, 59(2):309-313. McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. & Stadlan, E.M. (1984).Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology.34(7):939-44.Mackenzie, I.R., Neumann, M., Cairns, N.J., Munoz, D.G. & Isaacs, A.M. (2011). Novel types of frontal temporal lobar degeneration: beyond tau and TDP-43.Journal of Molecular Neuroscience, 45(3):402-408.Mathis, C.A., Wang, Y., Holt, D.P., Huang, G.F., Debnath, M.L. & Klunk, W.E. (2003).Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. Journal of Med Chem.46(13):2740-2754.Mattsson, N., Zetterberg, H., Hansson, O., Andreasen, N., Parnetti, L., Jonsson, M., Herukka, S.K., van der Flier, W.M., Blankenstein, M.A., Ewers, M., Rich, K., Kaiser, E., Verbeek, M., Tsolaki, M., Mulugeta, E., Rosén, E., Aarsland, D., Visser, P.J., Schr?der, J., Marcusson, J., de Leon, M., Hampel, H., Scheltens, P., Pirttil?, T., Wallin, A., J?nhagen, M.E., Minthon, L., Winblad, B. & Blennow, K. (2009). CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA, 302(4):385-393Mittelman, M.S., Haley, W.E., Clay, O.J. & Roth, D.L. (2006). Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology, 67(9):1592-1599.Nasreddine, Z.S., Phillips, N.A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J.L. & Chertkow, H. (2005). The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of American Geriatric Society, 53(4):695-699.Petersen, R.C., Thomas, R.G., Grundman, M., Bennett, D., Doody, R., Ferris, S., Galasko, D., Jin, S., Kaye, J., Levey, A., Pfeiffer, E., Sano, M., van Dyck, C.H. & Thal, L.J. (2005). Alzheimer's Disease Cooperative Study Group. New England Journal of Medicine, 352(23):2379-2388. Rascovsky, K., Hodges, J.R., Kipps, C.M., Johnson, J.K., Seeley, W.W., Mendez, M.F., Knopman, D., Kertesz, A., Mesulam, M., Salmon, D.P., Galasko, D., Chow, T.W., Decarli, C., Hillis, A., Josephs, K., Kramer, J.H., Weintraub, S., Grossman, M., Gorno-Tempini, M.L. & Miller, B.M. (2007). Diagnostic criteria for the behavioral variant of front temporal dementia (bvFTD): current limitations and future directions. Alzheimer Disease Associated Disorders.21(4):S14-8.Rossetti, H.C., Lacritz, L.H., Cullum, C.M. & Weiner, M.F. (2011). Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample. Neurology.77(13):1272-1275. Sperling, R.A., Aisen, P.S., Beckett, L.A., Bennett D.A., Craft, S., Fagan, A.M., Iwatsubo, T., Jack, C.R., Jr., Kaye, J., Montine, T.J., Park, D.C., Reiman, E.M., Rowe, C.C., Siemers, E., Stern, Y., Yaffe, K., Carrillo, M.C., Thies, W., Morrison-Bogorad, M., Wagster, M.V. & Phelps, C.H. (2011). Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7:280-292.Spitzer, R., Kroenke, K. & Williams, J. (1999).Validation and utility of a self-report version of PRIME-MD: The PHQ Primary Care Study. Journal of the American Medical Association 282: 1737-1744.Staekenborg, S.S., van der Flier, W.M., van Straaten, E.C., Lane, R., Barkhof, F., Scheltens, P. (2008). Neurological signs in relation to type of cerebrovascular disease in vascular dementia. Stroke, 39(2):317.Tariq, S.H., Tumosa, N., Chibnall, J.T., Perry, M.H. & Morley, J.E. (2006). Comparison of the Saint Louis University mental status examination and the mini-mental state examination for detecting dementia and mild neurocognitive disorder--a pilot study. Am J Geriatric Psychiatry. 14(11):900-10.Wallin, A.K., Blennow, K., Zetterberg, H., Londos, E., Minthon, L. & Hansson, O. (2010). CSF biomarkers predict a more malignant outcome in Alzheimer disease. Neurology, 74(19):1531-1537.Wechsler, D. (2009). WMS-IV Administration and Scoring Manual. San Antonio, Texas. The Psychological Corporation. Wolfs, C.A.G., Dirksen, C.D., Kessels, A., Severens, J.L. & Verhey, F.R.J. (2009). Economic evaluation of an integrated diagnostic approach for psychogeriatric patients: results of a randomized controlled trial. Arch Gen Psychiatry, 66(3):313-323.Yesavage, J. A., Brink, T. L., Rose, T. L., Lum,O.,Huang,V., Adey, M. B., & Leirer, V. O. (1983). Development and validation of a geriatric depression rating scale: A preliminary report. Journal of Psychiatric Research, 17, 37–49.ReviewsBudson, A.E. & Price, B.H. (2005). Memory dysfunction. New England Journal of Medicine. 352:692-69.Geschwind, M.D., Shu, H., Haman, A., Sejvar, J.J., Miller, B.L. (2008). Rapidly progressive dementia. Annals of Neurology. 64(1):97-108.Miller, B.L. & Boeve, B.F. (2009). The Behavioral Neurology of Dementia. Cambridge University Press.Rabinovici, G.D. & Jagust, W.J. (2009). Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behavior Neurology. 21(1):117-28.Websites and Web-Based ResourcesAlzheimer’s Association, 2013, Alzheimer’s Disease Facts and Figures Provider Practice Tool, ACT on Alzheimer’s in partnership with the Alzheimer’s Association: MN/ND Chapter Early Signs of Alzheimer’s Disease. Alzheimer’s Association. Functional Assessment Form. HYPERLINK "" A.Emerging Research Criteria and Alzheimer-Specific BiomarkersResearch relating to Alzheimer’s detection has progressed exponentially in recent years and may change the way providers diagnose the disease. The original National Institute for Communicable Disorders and Stroke-Alzheimer’s Disease and Related Disorders (NINCDS-ADRDA) criteria for the diagnosis of Alzheimer’s disease were published in 1984 (McKhann, 1984) to provide physicians and researchers guidance in AD diagnosis. The criteria divided Alzheimer’s disease into definite, probable, and possible. A diagnosis of “definite AD” required the combination of both “probable AD” and an autopsy confirmation of the diagnosis. ‘‘Probable AD’’ required deficits in two or more areas of cognition, including memory, that were progressively worsening, confirmed by clinical and neuropsychological evaluations, and not associated with either delirium or other brain or systemic illnesses that could be the cause of the dementia. The diagnosis was further supported by impaired function in activities of daily living (ADLs) and presence of behavioral dysfunction, and family history (particularly if supported by previous neuropathology). A diagnosis of ‘‘possible AD’’ included cases where there was a single progressively more severe cognitive deficit, a second brain or systemic cause for dementia, and atypical onset (early or with unusual symptoms and course [rapid or stuttering]).In 2011, the National Institute on Aging (NIA) and the Alzheimer’s Association recommended new diagnostic criteria and guidelines for Alzheimer’s disease (Sperling, 2011). The original 1984 criteria were based chiefly on a doctor’s clinical judgment about the cause of an individual’s symptoms, taking into account reports from the patient, family members and friends, results of cognitive testing, and general neurological assessment. The new criteria incorporated two notable changes:Addressed Application of Biomarker Tests. A biomarker is something in the body that can be measured and that accurately indicates the presence or absence of disease or the risk of later developing a disease. For example, blood glucose level is a biomarker of diabetes, and cholesterol level is a biomarker of heart disease risk. Levels of certain proteins in fluid (levels of beta-amyloid and tau in the cerebrospinal fluid and blood) or the presence of brain amyloidosis on PET imaging are among several factors being studied as potential biomarkers for AD. Identified a Preclinical Stage of AD in Addition to MCI and AD: a) preclinical AD is characterized by the presence of AD-related biomarkers and absence of cognitive symptoms such as memory impairment; b) MCI due to AD represents a state where there are subjective and objective findings suggestive of cognitive impairment with relative preservation of ADLs and IADLs; c) Dementia due to AD where there is impairment in both ADLs and IADLs in the setting of objective/subjective cognitive impairment. Both MCI and AD can be diagnosed and treated within the clinical setting whereas preclinical AD refers to a patient population identified only through the use of AD-related biomarkers in research investigations. Examples of such investigations include the Alzheimer’s Prevention Initiative (API) and Dominantly Inherited Alzheimer’s Network (DIAN) studies; please refer to Quality Interventions Module for more details on these clinical research programs.The New Criteria and Guidelines Identify Two Biomarker Categories: (1) biomarkers showing the level of beta-amyloid accumulation in the brain (e.g., amyloid imaging with PET technology as well as decreased CSF levels of Abeta 42) (Rabinovici, 2009; Mathis, 2003; Mattsson, 2009) and (2) biomarkers showing neuronal damage or neurodegeneration (e.g., elevated CSF tau, brain atrophy on structural MRI imaging, or decreased cerebral glucose update on FDG-PET imaging). Researchers believe that future treatments will be more effective in slowing or halting the progression of Alzheimer’s disease (referred to as “disease modifying” treatments) when administered during the preclinical and MCI stages of the disease. The primary use of AD biomarkers is currently experimental and inappropriate for routine evaluation, but they may increasingly become optional diagnostic tools when appropriate. The Role of FDG-PET Biomarkers in Clinical PracticeBrain FDG-PET (Flurodeoxyglucose-Positive Emission Tomography) is an imaging technique that primarily measures brain function in patients with Alzheimer’s disease and associated disorders. The process involves injecting patients with a radioactive fluorine-based isotope (F18) that is taken up by brain cells, revealing regions of normal cerebral activity and abnormal hypoactivity in the brain. The FDG-PET is a helpful tool to show the dysfunctional neuroanatomical regions responsible for the clinical presentation; in fact, studies have shown that regional glucose metabolism rather than amyloid deposition is better related to AD associated cognitive decline (Furst Neurobiol Aging, 2011). In an individual with AD, an FDG-PET scan will demonstrate metabolic reduction in the biparietotemporal cortices, posterior cingulate, and precuneus regions (Ishii, AJNR, Aug 2013) (refer to for images). A similiar pattern of hypometabolism has been demonstrated in both ApoE4 carriers (Reiman, EJM, 1996) as well as subjects with amnestic MCI (Mosconi Neurology, 2004), leading some researchers to suggest that FDG-PET has a greater sensitivity for AD detection than structural imaging with MRI or CT. Nevertheless, FDG-PET imaging should not be ordered routinely within clinical practice and should be reserved for complex cases such as distinguishing between AD and frontotemporal dementia, one of the few instances where the study costs will be covered by CMS ;. In The Future, Biomarker Tests will Potentially be Helpful for The Following: 1) identifying individuals within the earliest AD stages; 2) distinguishing AD from other types of dementia; 3) determining the optimal point at which to initiate medications; 4) assessing response to FDA approved and exploratory compounds through clinical trials; and 5) providing objective information to guide prognosis (Jack, 2011), (Wallin, 2010).The Role of Amyloid PET Biomarkers in Clinical PracticeThe development of a specific radioligand for fibrillar amyloid (Pittsburgh Compound B) represented a significant research milestone, thus enabling detection of amyloid plaques in living patients whereas previously, confirmation of cerebral amyloidosis required a post-mortem examination (Klunk Annals Neurology, 2004). The procedure involves intravenous administration of an amyloid-binding radioisotope to the subject and visualization of the cerebral amyloid plaques with a PET scan. Thus, this technology has been referred to as amyloid-PET imaging. The first amyloid imaging agent, a radioactive carbon isotope (C11), was limited to academic institutions with a cyclotron as the product’s half-life was only 20 minutes (Wolk JNNP 2012). FDA approval of radioactive fluorine agents with longer half-lives (approximately 110 min), first with flobetapir (F18) (Amyvid) in November 2012, followed by flutametamol (Vizamyl) in October 2013, has enabled dissemination of this technology to a growing number of medical institutions (Yang, NEJM, 2012). Although current use of amyloid-PET imaging is not recommended for routine diagnosis of AD, there have been several recent developments indicating a gradual movement toward transitioning amyloid-PET imaging from the research to the clinical setting. Recognizing the inevitable Pandora’s box associated with in vivo amyloid detection, researchers convened an Amyloid Imaging Task Force responsible for making recommendations about appropriate use of amyloid imaging in clinical practice (Johnson, Nucl Med, 2013). Firstly, the patient should have a cognitive complaint with objectively confirmed impairment, an uncertain diagnosis after evaluation by a dementia expert, and an expectation that knowledge of A status would increase diagnostic certainty and/or alter management. The Task Force provides guidance on the appropriate and inappropriate use of amyloid imaging in a variety of hypothetical case scenarios, which are listed below:Appropriate Use:Patients with persistent or progressive unexplained MCI;Patients satisfying core clinical criteria for possible AD because of unclear clinical presentation, either an atypical clinical course or an etiologically mixed presentation.Patients with progressive dementia and atypically early age of onset (usually defined as 65 years or less in age) Inappropriate Use: Patients with core clinical criteria for probable AD with typical age of onsetTo determine dementia severityBased solely on a positive family history of dementia or presence of apolipoprotein E (APOE) ?4 Patients with a cognitive complaint that is unconfirmed on clinical examinationIn lieu of genotyping for suspected autosomal mutation carriersIn asymptomatic individualsNonmedical use (e.g., legal, insurance coverage, or employment screening)The question of whether amyloid imaging in dementia impacts clinical outcomes or medical decision-making has been minimally addressed by current research. An isolated study compared the utility of amyloid-PET with FDG-PET imaging at an academic center, finding that amyloid imaging had a greater impact on diagnosis and treatment than FDG-PET (Sánchez-Juan Neurology, 2014). Studies have also shown that a combination of amyloid and FDG-PET imaging increases the predictability of MCI converting to AD compared to amyloid-PET alone (Prestia Neurology, 2013). However, the results from amyloid PET imaging should be interpreted with caution; there has been evidence that cerebral amyloidosis is necessary, but not sufficient for AD and that this process develops independent of disease-associated neurodegeneration (e.g. brain cell death and cerebral atrophy related to neurofibrillary tangles) (Knopman Neurology, 2014). In addition, studies have also shown that 15-30% of subjects with amyloidosis on PET imaging lack the characteristic cognitive symptoms found in AD (Jack Brain, 2008; Morris Ann Neurol, 2010). The Center for Medicare and Medicaid Services (CMS) ruled in January 2013 that there was insufficient evidence to conclude that the use of positron emission tomography (PET) amyloid-beta (Aβ) imaging is “reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member for Medicare beneficiaries with dementia or neurodegenerative disease, and thus PET Aβ imaging is not covered under §1862(a)(1)(A) of the Social Security Act (“the Act”).” CMS did note that exceptions could be made in certain clinical trials seeking better treatment or prevention strategies in AD. For more information on the CMS decision, refer to the following website: . Healthcare providers should expect to face questions about amyloid imaging from patients with memory complaints; the out of pocket cost for an amyloid imaging study amounts to $3000/image. For more information regarding the role of amyloid imaging in clinical practice, please refer to the following website: addition to amyloid-specific tracers, there has also been an effort to evaluate the tau-based neurofibrillary tangles associated with AD with the tau-binding agent T807 (Chien JAD 2013). Preliminary work has shown that this agent may detect tau, but also exhibits non-specific binding. Additional investigations will be necessary to better evaluate the practical application of T807 in both the clinical and research settings. The Role of Cerebrospinal Biomarkers in Clinical PracticeThe evaluation of cerebrospinal fluid (CSF) in patients with dementia has been reserved for individuals presenting with suspected infectious and autoimmune causes of their clinical syndrome. For instance, a spinal tap for CSF is routinely performed in patients presenting with meningitis. It has been shown that the evaluation of specific CSF proteins may be used to confirm and possibly identify AD in the earlier stages. These protein include the following:A-42: This protein is a component of the amyloid plaques found in the AD brain and decreased levels are considered suggestive of Alzheimer’s (Blennow, Lancet Neurol, 2003). It is thought that the decline in CSF A-42 represents sequestration of this protein to the senile plaque. Tau: Tau is a microtubule-associated protein that forms the neurofibrillary tangles in AD and CSF levels are expected to increase with an AD-related process (Andreasen N World J Biol Psychiatry 2003). It also serves as a marker of cellular injury for other neurodegenerative diseases.Phospho-tau:Phospho-tau is the hyperphosphorylated and abnormal form of tau that eventually is incorporated into neurofibrillary tangles. Phospho-tau levels increase when AD develops in the brain (Hampel, Neural Transm, 2004). These proteins are almost exclusively measured together, and the hallmark AD profile includes decreased CSF A42, elevated tau, and increased phosphotau. Individuals with an MCI diagnosis have an increased risk of progressing to AD compared to those lacking these changes (Diniz, World J Biol Psychiatry, 2008; Mattsson, JAMA, 2009; Hannsson, Lancet Neurol, 2006). CSF analysis for AD has several limitations. First of all, this procedure involves exposing patients to a relatively invasive procedure where spinal fluid is removed from the back. Considering that AD affects 5.4 million individuals in the U.S. with the expectation that this number will triple by 2050, performing spinal taps on all patients with suspected AD has practical limitations. In addition, there are no standardized protocol or performance criteria regarding the laboratory techniques necessary to determine CSF biomarker results (Mattsson, Biomark Med, 2012). Thus, results of a single sample may vary significantly between laboratories and are presented in various forms depending on the institution. Thus, this dilemma challenges the clinician’s ability to effectively utilize this information. Certain researchers use an A threshold as <550, a tau threshold of >350, and a phosphotau threshold >60 to indicate the AD profile. In addition, results are presented in different ways between laboratories.Conclusion The role of PET imaging and CSF biomarkers in clinical practice remains to be defined as AD can be diagnosed independently of these diagnostic techniques. However, their utility for patients with memory disorders may change once it is shown that earlier intervention with pharmacological and/or non-pharmacological approaches will improve clinical outcomes and healthcare utilization among such individuals. ................
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