ACT on Alzheimer’s



ACT on Alzheimer’sAlzheimer’s Disease CurriculumModule VIII: Quality InterventionsGUIDELINES 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: VIII: Learning ObjectivesUpon completion of this module the student should:Have a basic knowledge of pharmacological and non-pharmacological interventions.Identify a variety of interventions that can be used with a person who has a diagnosis of Alzheimer’s disease.Gain insight on how physical, cognitive, and social activities along with diet can be used as positive interventions.Develop a familiarity with evolving strategies and clinical trials for the continuum of Alzheimer’s disease.Module VIIICase 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.Quality Interventions Intervention GoalsCurrent treatment for Alzheimer’s disease (AD) is symptomatic, and there are no treatments that serve as preventative or disease-modifying therapies. All available FDA-approved pharmacotherapy for AD is targeted toward cognitive or behavioral symptoms. That being said, there are numerous interventions that may impact quality of life, delay institutionalization, and prevent medical crises. View the following video for more information: individuals with dementia receive their medical care from primary care physicians (PCPs) (Callahan et al., 2006) who have minimal training or experience regarding the care of cognitively impaired individuals. In addition, the prevalence of AD is expected to triple from the current 5.4 million by 2050. Therefore, primary care physicians and other health care providers must approach care for individuals with AD with the goals of providing quality interventions that can reduce the severity of the disease, delay institutionalization, prevent medical crises, and improve quality of life. Refer to the following video for more information: quality interventions that can be provided to individuals with AD are divided into the pharmacological and non-pharmacological type. In the medical profession, there has traditionally been an emphasis on drug therapies, but as a result of the limited impact of AD-approved medications on disease progression, education and support services serve as the foundation for quality intervention in AD. ACT on Alzheimer’s developed a comprehensive practice tool for the full disease continuum that addresses the topics above and 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. Both tools can be accessed at . This module will discuss each of the categories subsumed under the pharmacological and non-pharmacological categories as listed below.Non-Pharmacological InterventionCounseling, Education, Support, & PlanningStimulation/Activity/Maximizing FunctionSafetyAdvance Care PlanningReferral to neurologist or geriatrician for diagnostic uncertainty or behavioral managementPharmacological InterventionMedications for Cognitive SymptomsMedications for Behavior and Neuropsychiatric Symptoms (if indicated)Antidepressants Anti-insomnia medications Neuroleptics Contraindicated medicationsVitamins and SupplementsDescription of Non-Pharmacological InterventionsOver 40 non-pharmacological interventions and care practices have shown positive outcomes in randomized controlled trials (RCTs) conducted in the United States. The Administration on Aging has produced a report summarizing these studies as well as their implementation in the field : Counseling, Education, Support, & Planning with Newly Diagnosed PeopleEducation and support services for individuals with dementia and their families/caregivers are critical for sustained management of dementia. In addition to the benefits of education, support, and counseling for caregivers (addressed in detail in the Caregiver Support Module), these interventions directly benefit individuals in the early and mid-stages of the disease (Family Caregiver Alliance, 2006). Numerous healthcare providers participate in the counseling, education, and support process, starting with the primary care provider, nurse practitioners, nurses, social workers, occupational therapists, and community organizations. Research and clinical practice establish that counseling, education, and support services to individuals in early stages of the disease, and to caregivers throughout the disease, may result in the following direct benefits for care: 1) reducing behavioral symptoms; 2) promoting compliance with treatment plans; 3) providing a support system for people who often feel isolated from their communities, family, and friends; 4) improving moods in individuals with the disease and their family members; and 5) delaying institutionalization (Doody, 2001), (Guerriero, 2004), (Gallahger-Thompson & Coon, 2007), (Mittleman, 1996), (Mittleman, 2004), (Mittelman, 2006), (Mittelman, 2007), (Callahan, 2006), (Cherry 2004), (Pinquart & S?rensen, 2006), (Vickrey, 2006). The primary provider serves an important function in the education process and referral for counseling and other supportive services. To ensure appropriate attention to counseling, education, support, and planning for the individual with dementia and the caregiver, the provider should:Discuss diagnosis and treatment with the individual with dementia and the caregiver, including goals of care, progression of the disease, treatment options, and specific diagnosis.Encourage the caregiver and individuals in the early to mid-stages of the disease to participate in educational programs, support groups, respite services, and adult day service programs (American Psychiatric Association Guidelines, 2007), (Lyketsos 2004, 2006).Involve individuals in early stages of the disease in care planning and enable them to make decisions to the greatest extent possible throughout the course of the disease.Address caregiver support on an ongoing basis and assess caregivers’ mental and physical health regularly (Guideline for Alzheimer’s Disease Management. California Workgroup on Guidelines for Alzheimer’s Disease Management, Final Report 2008). care with education and support by connecting individuals with the disease and their caregiver to community-based organizations that provide support, e.g., Alzheimer’s Association and local community-based support service organizations. Optimally, primary care providers should have established and formal partnerships with such providers to facilitate effective referral, seamless services, and appropriate information sharing.Referral to Community-Based ServicesOne of the major challenges for the primary care physician is providing the necessary counseling within a limited amount of scheduled time to the individual with AD. The community-based organization is another resource that can supplement the interventions performed by the primary care provider. The primary care provider plays a critical role in directing individuals with dementia and their caregivers to services and resources that may improve the quality of life for both the individual with dementia and the caregiver (Lyketsos et al., 2006), (Winslow, 2003). Community-based organizations provide a variety of services, including counseling, education, support, planning, care management/coordination, physical activity, cognitive stimulation, advanced care planning, medication management, respite care, and home, safety, driving, and legal/financial services. Providers will be best served by seeking out and forging relationships with local community-based providers in areas where they will need to refer to quality interventions. Formal partnerships will assure seamless care, effective exchange of information, and cohesive and comprehensive management across a spectrum of services. One of the most important roles of the community-based organization is assisting individuals with AD and families with finding support groups and adult day programs. Studies show that support groups for early stage dementia offer individual and family members opportunities to share and make sense of their experiences while reducing burden and emotional distress (Zarit, 2007) and (Cheston, 2003). Researchers have also found positive effects of support group settings offering education, therapy, and psychosocial support on cognition, affect, health, self-esteem, and stress in individuals with AD and families (Buettner, 2006) (Buettner, 2009). An optimal model for this approach includes a combination of education and supportive peer discussions involving either early-stage individuals only or both those affected and their care partners in parallel groups (Yale, 1995), (Alzheimer’s Association, 2007). As the disease progresses, adult day programs offer a combination of cognitively stimulating activities and have been shown to benefit persons with dementia (Femia, 2007). Adult day programs are one of the best care settings for the individual with moderate-severe dementia living in the community. As compared to families not participating in adult day programs, caregivers of individuals with dementia using adult day services report decreased behavioral symptoms and time spent managing such symptoms. Other positive aspects of adult day care include less time spent managing memory difficulties and impairments in activities of daily living, decreased caregiver burden, and elimination of recreational restrictions (Gaugler 2003a-b), (Zarit, 1998), (Schacke & Zank, 2006). Consequently, caregivers utilizing the adult day program option report a better relationship with the affected individuals (Dziegielewski, 2000). From a public health perspective, adult day service is an important service in that it may delay nursing home placement (Zarit, 1998) as well as the ensuing cognitive decline should the individual eventually be placed in a nursing home (Wilson, 2007). ACT on Alzheimer’s Tools: 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.The Care Coordination Practice Tool supports the coordination of care of patients with dementia and their care partners or caregivers. The Electronic Medical Record (EMR) Decision Support Tools provides a template to assist clinicians in implementing a standardized approach to all aspects of dementia care within the health record: screening, diagnosis, and treatment management. The tools may be used within a variety of EMR products and can be modified to meet the unique needs of each healthcare system. Stimulation/Activity/Maximizing FunctionAlthough the medical establishment has traditionally focused on certain drugs, such as Aricept and Namenda for treatment of AD, there are multiple lifestyle changes such as physical activity, cognitive activity, social activity, and a healthy diet that may optimize function in individuals with AD. Physical Activity Research suggests that moderate physical activity can positively impact mood, sleep, functional ability, and cognition (Baker et. al., 2010), (Burns et al., 2008), (Eggermont et al., 2006), (Lautenschlager et al., 2008), (Williams & Tappen, 2007). The majority of beneficial activities studied in the literature are aerobic in nature (e.g., brisk walking, hiking, aerobics, strength training, swimming, tennis doubles, yoga, martial arts, weight lifting, and golfing without a golf cart, and moderate use of exercise machines [e.g., exercise bike, treadmill, elliptical]), yet there are ongoing studies looking at less intensive exercises such as Tai Chi (Lam, 2011). Exercise at least three times per week in mid- and late-life has been shown to result in decreased risk for cognitive impairment, Alzheimer’s dementia, and dementia in longitudinal cohort studies (Laurin, 2001), (Etgen, 2010), and (Geda, 2010). A dose-response relationship between exercise and decreased dementia risk has been demonstrated through longitudinal studies (Weuve, 2004). A consistent benefit has been shown specifically for Alzheimer’s disease and associations are less robust for vascular dementia (Rockwood, 2007). The benefits of exercise for cognition appear to be greater in women compared to men for unknown reasons (some authors have suggested modification of the hypothalamic-pituitary-adrenal axis) (Colombe, 2003). Randomized controlled trials have demonstrated a benefit of exercise in mild cognitive impairment (MCI) and normal aging subjects. The specific cognitive modalities influenced by physical exercise involved aspects of executive function (selective attention, planning, organizing, multitasking, inhibition, and working memory) (Colombe, 2003). More specifically, clinical trials have demonstrated that using a treadmill for goal heart rate 75-85% of maximum for 45-60 minutes per session four times per week results in cognitive benefits in MCI subjects (Baker, 2010). The therapeutic effects of physical activity may be apparent in as little as 4 months following an exercise regimen (Rockwood, 2007) and may be sustained as long as 12 months after stopping the program (Lautenschlager, 2008). There is evidence that exercise may be beneficial for the later AD stages. A study involving 90 nursing home residents with mostly moderate-to-severe Alzheimer’s disease found that participation in a comprehensive group exercise program resulted in significantly greater improvement in mood than either supervised walking or non-therapeutic conversation groups (Williams, 2007). Research is also emerging that increased physical activity may ameliorate some of the negative physical consequences associated with dementia such as risk for falls and fractures, loss of muscular endurance, and cardiopulmonary function, as well as improve ADL function and mood (Teri, 2008). The development of an exercise regime may benefit physical function without significantly increasing healthcare costs (Pitkala, 2013).The mechanism by which exercise improves cognitive function may involve increasing levels of CNS BDNF that ultimately result in hippocampal neurogenesis (particularly in the anterior hippocampus) as well as optimization of cerebral perfusion (Black, 1990), (Van Praag, 2005). Studies have even demonstrated increased hippocampal volume following aerobic exercise in cognitively normal adults (Erickson, 2011). Ideally, individuals with dementia should be referred to stage specific wellness and risk reduction programs including adult day services, exercise clubs, therapy referrals (OT, PT, Speech), and clinical evaluation for sensory aids (vision, hearing). Specific evidence-based programs include:Healthy Moves for Aging Well: An in-home physical activity intervention to enhance the activity level of frail, high-risk, sedentary seniors living at home. The model was developed for community-based care management programs (Yan, 2009).Chronic Disease Self-Management Program: A program that people with different chronic diseases attend together to learn skills needed in the day-to-day management of treatment and to maintain and/or increase life’s activities (Lorig, 2001).EnhanceFitness?: A low-cost, evidence-based group exercise program, that helps older adults at all levels of fitness become more active, energized, and empowered to sustain independent lives (Wallace, 1998).Healthy Eating for Successful Living in Older Adults: A program for diverse community-dwelling adults age 60 and older with an overall goal of increasing self-efficacy and general well-being by improving participants' knowledge of nutritional choices that focus on heart and bone healthy foods as well as supportive physical activities (National Council on Aging Center for Healthy Aging, 2006).Tai Chi: A traditional Chinese mind-body exercise program whose participants were found to have better arterial compliance and greater muscle strength than non-practitioners (Lu, 2012).Cognitive ActivityParticipation in cognitive-oriented activities in late life is thought to maximize cognitive reserve in the setting of AD-related pathology by enhancing neurogenesis and synaptogenesis. Observational studies have suggested that cognitive leisure activities in the elderly such as reading, writing, completing crossword puzzles, playing board/card games, playing musical instruments, participating in group discussions, and dancing are associated with a decreased risk of MCI, Alzheimer’s, and vascular dementia (Verghese, 2003, 2006). Furthermore, these activities have shown to reduce decline in global cognition, perceptual speed, and working memory (Wilson, 2002). The theory is that increased cognitive activity may protect against AD-related pathological changes by increasing brain adaptability and cognitive reserve (Stern, 2006). These studies are limited in that they have found a direct relationship between the activities as a group and cognitive decline as opposed to a relationship between individual activities (e.g., playing an instrument) and cognitive decline. Furthermore, it is unclear whether participation in cognitively stimulating tasks protects against or is influenced by the onset of neurodegenerative disease. Nevertheless, it is recommended that all individuals with MCI or AD pursue a daily leisure activity, like those listed above, that is most interesting to them. Additionally, cognitive training for persons with early stage dementia is likely to be helpful for managing symptoms of dementia (Yu 2009). Finally, the provider should ensure optimal vision and hearing with use of aids so that the individual with AD may optimally participate in cognitively-related activities. A variety of Minnesota-based programs exist to provide individuals with memory loss a framework for cognitive stimulating activities:The Living Well Program: . Healthy Action to Benefit Independence and Thinking (HABIT): there is minimal outcome data studying the impact of web-based cognitive training programs, there are several online sites that offer a variety of exercises that are derived from neuropsychological testing. Future investigations will need to evaluate the overall impact of these interventions on outcomes in dementia. The most commonly recommended websites include and Activity Similar to cognitive leisure activity, increased social networks in late life may benefit individuals with MCI and AD by increasing cognitive reserve. Longitudinal and cross-sectional studies have shown that lacking social network connections to friends and family in mid as well as late life is associated with increased dementia risk ranging from RR1.6-3.4 (Scarmeas, 2003), (Fratiglioni, 2007), (Seidler, 2003), (Helmer, 1999), (Fratiglioni, 2000). There may be an underlying physiological mechanism to participation in social activities resulting in increased cognitive reserve against cerebral amyloid accumulation. However, most investigations have only demonstrated an inverse association between late-life socialization and dementia risk, and therefore, it is unclear whether social ties protect against or are initially compromised by progressive cognitive dysfunction. Diet Greater adherence to the Mediterranean diet is associated with decreased risk of developing MCI and conversion from MCI to Alzheimer’s disease (Scarmeas, 2006), (Scarmeas, 2009). The exact mechanism by which the Mediterranean diet decreases AD risk is unknown, but it has been hypothesized that these foods reduce markers of oxidative stress such as isoprostanes through antioxidant activity and improve carbohydrate metabolism (Singh, 2002), (Mancini, 1995). This diet is characterized by a higher intake of salad dressing; nuts; fish; tomatoes; poultry; cruciferous vegetables; fruits; dark, green, leafy vegetables; and lower intakes of high-fat, dairy products, red meat, organ meat, and butter (). Subjects adhering to the Mediterranean diet make fewer errors on the MMSE (Feart, 2009). Consumption of fish, a stable item found in Mediterranean cooking, has been associated with decreased risk of MCI (Barberger-Gateau, 2002). However, clinical trials focusing on major nutrients within the diet have failed to demonstrate consistent cognitive benefits. For instance, a trial of omega 3 fatty acids in healthy elderly subjects did not show any effect of this supplement in the treatment compared to the placebo group during a two-year period (Dangour, 2010). Additionally, trials of omega 3 fatty acids (DHA, docosahexanoic acid and eicosapentaenoic acid) in mild-moderate AD subjects have failed to demonstrate any benefit of this supplement in slowing decline compared to controls (Freund-Levi, 2006), (Quinn, 2010). Thus, there is no evidence for recommending omega 3 fatty acid supplements in individuals with MCI, mild AD, and moderate AD. At the same time, adherence to the Mediterranean diet has consistently been shown to be associated with reduced cognitive decline in NC, MCI, and AD, and therefore, other mechanisms may underlie the cognitive protective nature of this cuisine. For more information regarding the Mediterranean diet recipes, please refer to the following web link: Regarding SafetyLegal/Financial PlanningThe clinical and community-based provider plays a critical role in providing guidance to individuals with dementia and their families regarding the need for financial and legal advice (Ham, 1997), ( Lyketsos, et al., 2006). Financial planning is considered a safety issue due to the relatively high frequency of functional deficits in managing finances within the AD population. Clinical and community-based providers should encourage and facilitate individuals with dementia to engage in legal and financial planning if the individual has decision-making capacity (Overman, 1988). Recommendations should include consultation with financial advisors and legal counsel with discussion of conservatorship (American Psychiatric Association, 2007). Individuals should be encouraged to execute Durable Powers of Attorney as appropriate and be referred to an elder law attorney or another organization that can make such a referral, such as the Alzheimer’s Association (Taking Action Workbook, Alzheimer’s Association 2010; National Academy of Elder Law Attorneys (NAELA) ).DrivingDriving is a common issue that should be discussed with any person diagnosed with AD. As a result of compromise in executive function, visuospatial function, and visual memory, individuals with AD have relatively higher risk of motor vehicle accidents. Poor performance on the Trail Making B test is associated with motor vehicle crashes. That being said, a diagnosis of AD does not necessarily preclude a person from driving, and based on performance on formal testing, a decision can be made whether the individual can drive without restrictions, with restrictions, or not at all. Certain institutions have formal driving evaluations offered through physical or occupational therapy, but this service may also be obtained through community-based providers who discuss the risks of driving and refer to appropriate resources, including "Senior Citizen Driving" by at At the Crossroads: Family Conversations about Alzheimer’s Disease, Dementia, and Driving ; and Dementia & Driving Resource Center HYPERLINK "" . The primary care provider should have a low threshold to counsel the individual against driving should there be any concern about driving ability prior to formal testing. Home SafetyClinical and community-based providers should refer to community organizations that can assess an individual’s home environment to ensure safety and security, including assessment of falls risk and ensuring proper grab bars in bathrooms and kitchens. Home assessments could also identify environmental conditions that may trigger difficult behaviors such as wandering. For more information regarding home safety, please refer to ManagementClinical and community-based providers should ensure that treatment plans include medication management support, either through an individual’s caregiver or home health care agency. In addition, occupational therapy as well as pharmacy consultation at certain institutions may be helpful in assessing the person’s ability to comply with medical regimen instructions as well as providing suggestions for improving medication adherence.Behavioral Issues There are numerous non-pharmacological interventions for AD-related behavioral disturbances that should first be attempted prior to administering neuroleptic agents. While the evidence is still emerging (Hermans, 2007), (Hogan, 2007), (Logsdon, 2007), non-pharmacological strategies often better address the underlying reason for the behavior, avoid both the risks and limitations of pharmacological interventions, and prevent medicating away adaptive or helpful behaviors (Gitlin, et. al., 2012), (Cohen-Mansfield, 2001). Although non-pharmacological interventions are a preferred approach as a first line of treatment for behavioral symptoms (e.g., the American Academy of Neurology (Doody et al., 2001), American Association for Geriatric Psychiatry (Lyketsos et al., 2006), and American Psychiatric Association 2007), limited trials of such nonpharmacological interventions such as music therapy (Vink, et al., 2003), aromatherapy (Ballard, et al., 2002), bright lights (Forbes, et al., 2004), massage and touch (Viggo, et al., 2006), validation (Neal & Barton Wright, 2003), (Tondi, et al., 2007), and reminiscence (Woods, et al., 2005) have been performed but are not conclusive. Successful management of behavioral symptoms require a primary provider to develop appropriate and individualized care plans that are re-evaluated regularly (Gitlin, et. al., 2012), (Logsdon, 2007), (Sink, 2005). Effectively addressing behavioral issues starts with identifying the behavior, addressing the underlying cause, and adapting a care plan to remedy the situation (Cherry, 1997), (Woods, 1996). Addressing the underlying cause is one of the most important parts of the intervention. For instance, environmental changes are commonly a catalyst for difficult behaviors. Another cause of irritability may be frustration over an inability to communicate. Additionally, a new task or an unpopular task may trigger negative behavior responses. Each of these examples can be remedied through a responsive plan of action.The Cues and Clues model can be used to help assess and modify behaviors . The model uses a list of questions to help pinpoint the potential cause of the behavior as well as what steps may be taken in the future to avoid a repeat of the problematic conduct. This is the list of questions that comprise the cues and clues model:Who is the person?What is the behavior that concerns us and what is it related to?When does it happen?Where does it happen?Who is with the person when it happens?Why does it happen?Does the action need to change or can we live with it?If it needs to change, what can we do? How many potential solutions can we come up with? Any intervention should focus on ensuring safety, simplifying the environment, establishing routines, and distracting rather than confronting, arguing, or disagreeing with the individual (Teri, 2002). The following tips listed below are helpful in avoiding escalation of behavioral disturbances in dementia: Intervene early. Remain calm, using a gentle, reassuring voice, and maintain eye contact.Get the person’s attention by saying their name and offering an A/B choice or stating what you are doing so as not to surprise the person.Provide the individual with a structured, predictable routine (exercise, meals, and bedtime should be routine and punctual).Use visual cues or barriers to discourage wandering and direct the individual away from unsafe areas.Explain all procedures and activities slowly and in simple, straightforward terms.Simplify tasks by breaking them down into easy, manageable steps.Allow individuals to dress in their own clothing and maintain possessions.Use calendars, clocks, labels, or newspapers for orientation to time.Reduce excess stimulation, including noise from TV and household clutter.Avoid glare from windows and mirrors. Provide a safe environment free of sharp-edged furniture, slippery floors or throw rugs, and obtrusive electric cords.Equip doors and gates with safety locks.Install grab bars by the toilet and in the shower.Use lighting to reduce confusion and restlessness at night.Use distraction and redirection of activities.Provide music of the individual’s choosing, especially during meals and bathing (Guideline for Alzheimer’s Disease Management California Version, 2008). Advance Care PlanningGenerally, there is a lack of understanding of end-of-life care among the general population. (Silveira, 2000). Therefore, it is important for the primary provider and other care providers to discuss end of-life treatment goals and options with individuals with dementia and their families earlier in the disease process (Kettl, 2007). End-of-life treatment options and decisions need to take into account effective pain management and the goals of the individual with dementia via advance directive (Guideline for Alzheimer’s Disease Management California Version, 2008). Issues of informed consent and capacity may arise after a dementia diagnosis, especially with respect to executing legal documents and making care decisions such as those involved in advanced directives. Informed consent for purposes of making decisions regarding care is defined as understanding the nature of the diagnosis, the prognosis, and what course of treatment is to be expected (Overman, 1988). Capacity to make medical decisions involves ability to understand, reason about, and appreciate the consequences of the disease and particular course of treatment, and to communicate a choice of treatment, all of which decline as Alzheimer’s disease progresses (Huthwaite, 2006). Thus, clinical and community-based providers should refer individuals with dementia to advance care planning resources to assure that they have tools and can execute documents that will guide their care when they are no longer capable of doing so. It is generally recommended that conversations about advanced directives take place earlier rather than later in AD, due to the disease’s progressive effects on higher order decision-making. Resources include an advanced care planning facilitator’s form and/or online healthcare directive forms (Minnesota Healthcare Directive: ; Five Wishes: forms/5wishes.pdf; Honoring Choices Minnesota: ).A comprehensive practice tool for the full disease continuum that addresses the topics above can be accessed at . Description of Pharmacological InterventionsMedications for Cognitive SymptomsThe cholinesterase inhibitors (AchE-Is) serve as the cornerstone for pharmacotherapy in AD. Individuals with AD demonstrate decreased cholinergic neurons and cerebral production of choline acetyl transferase (ChAT), which leads to a cholinergic deficiency and cognitive changes (Whitehouse, 1982). Cholinesterase inhibitors were developed as treatments after it was recognized that cholinergic deficiency worsened AD symptoms. The AchE-Is exert their beneficial effects through the inhibition of acetylcholinesterase, resulting in an increase in acetylcholine within the synapse (Farlow, 2007). There may be further modest reduction on neuropsychiatric symptoms as well as the cognitive improvements. Although these agents may result in either stabilization or enhanced performance on cognitive screening tests, their mechanism of action in no way impacts the pathogenesis of AD and studies have shown no impact on disease course (Rogers, 1998). The impact on institutionalization, disability, and long-term outcome is unclear. One study suggested there may be lowered home care costs and delayed nursing home placement as a result of treatment with these medications (Neumann, 1999). Ultimately, the benefits of this drug class are modest and it is important that the individual with AD and the family be educated that these agents are by no means considered panaceas. FDA-approved cholinesterase inhibitors include donepezil (Aricept), a selective acetylcholinesterase; rivastigmine (Exelon), which also inhibits butyrylcholinesterase; and galantamine, a drug that further modulates the nicotinic receptor (Farlow, 2007). Tacrine was the first AchE-I approved for AD, but it is not widely used due to hepatotoxicity (Watkins, 1994). There is no data favoring one cholinesterase inhibitor over another in the treatment of AD. In addition, these medications have demonstrated efficacy for the cognitive and neuropsychiatric symptoms associated with Lewy body dementia (LBD) (McKeith, 2000) and vascular dementia (Erkinjntti, 2004). There is no role for AchE-Is in the frontotemporal dementia (FTD) spectrum disorders, and in fact, this drug class may worsen symptoms in such individuals (Mendez, 2007). The decision to start an AchE-I in the setting of mild cognitive impairment (MCI) is controversial, and further studies are necessary to address the cost-benefit of these drugs in the pre-dementia state. Double-blind, placebo-controlled trials have demonstrated that donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) have the potential to mildly improve cognition, activity of daily living (ADL) function, and behavior in individuals with mild- to moderate-stage AD for periods of between 6 and 18 months (Doody et al., 2001), ( Rogers, 1998). Donepezil is the only cholinesterase inhibitor that is FDA-approved for treating individuals with moderate-severe AD (Feldman 2001), (Tariot, 2001), (Winblad, 2006), (Black, 2007), although studies also have suggested a role for galantamine (Burns, 2009). Both the AD 2000 Collaborative Group study and the Alzheimer’s Disease Cooperative Studies–Mild Cognitive Impairment Trial indicate that donepezil may be less effective after 18 to 24 months (Courtney, et al., 2004), (Petersen, et al., 2005). However, there have been open label studies that suggest that AchE-Is may have sustained benefit for at least four to five years (Farlow, 2007). The decision to stop an AchE-I should be made cautiously as individuals with AD may experience altered mental status upon medication withdrawal (Rainer, 2001). In general, AchE-Is are well tolerated and the most common associated side effect is gastrointestinal upset in 20% of individuals (Rogers, 1998). Other side effects include vivid dreams, cramps, weight loss and decreased appetite, and in a small portion of individuals bradycardia with dizziness symptoms. Typically, individuals should follow-up within 1 month of starting the AchE-I at the lower dose (eg. donepezil 5 mg), titrating the drug upwards after 1 month if well tolerated. Individuals who exhibit adverse side effects related to AchE-Is may better tolerate the rivastigmine patch. The titration schedule for rivastigmine and galantamine is similar, starting with the lower dose and increasing to the maximum dose after one month. As AD progresses to the moderate stages, one can consider the use of memantine (Namenda). Memantine can be used by itself or in conjunction with an AchE-I. (Howard, et. al., 2012). This drug acts as an antagonist at the neuronal glutamatergic NMDA receptor, potentially improving signal transmission and interrupting pathways that may result in cell death. Despite this mechanism, there is no evidence that demonstrates any impact of this drug upon disease progression. In clinical trials, memantine has resulted in mildly improved cognition, behavior, and functional deficits (Reisberg, 2003).Preliminary studies have suggested that combination therapy with an AchE-I results in synergistic effects (Atri, 2008), leading some specialists to prescribe memantine during the earlier stages, yet these findings have not been replicated. Although frequently used off-label for mild AD, memantine shows minimal evidence for benefit in the early stages of dementia (Schneider, 2011), and a recent mild-moderate AD trial primarily intended to study vitamin E efficacy showed memantine with vitamin E or memantine alone did not have any effect on functional decline compared to placebo (Dysken, 2014) In general, memantine is a well-tolerated drug with few serious reactions and mild side effects of dizziness, headache, and confusion (McShane, 2006). For more information regarding specific pharmacotherapy of AD, please refer to for Behavioral and Neuropsychiatric SymptomsWith the progression of AD, the healthcare provider is bound to encounter neuropsychiatric disturbances in approximately 61%-92% of individuals that occur as a result of dysregulation of GABA-ergic, serotonergic, and noradrenergic neurotransmitter systems (Sink, 2005), (Mega, 1996), (Lyketsos, 2000). These disturbances include irritability, agitation, disinhibition, wandering, delusions, hallucinations, anxiety, depression, and sleep disruption (Mega, 1996). Behavioral symptoms are the major causes of excess disability, individual distress, caregiver burden, and institutionalization (Conn & Thorpe, 2007).Approximately 30% of individuals with AD suffer from depression, and treatment with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI) is indicated (Farlow, 2007). The depression may be related to pathological AD-related brain changes or secondary to progressive cognitive impairment. The development of apathy associated with AD may be mistaken for depression by family and healthcare providers. Commonly used medications for depression in AD include citalopram (Celexa), escitalopram (Lexapro), sertraline (Zoloft), and mirtazepine (Remeron). Generally, paroxetine (Paxil) is contraindicated due to anticholinergic actions. The FDA has recently recommended against prescribing citalopram doses > 40 mg due to risk of prolonged QT syndrome (). During the moderate-severe stages of AD, the individual may have increasing symptoms of irritability, agitation, and psychosis (delusions and hallucinations). Visual hallucinations are more commonly associated with Lewy body dementia (LBD), but may be observed in 20% of individuals during the later stages of AD. There may be modest benefits of an antidepressant in such individuals prior to starting a neuroleptic or antipsychotic agent. Commonly used neuroleptics in AD include quetiapine (Seroquel), risperidone (Risperdal), and olanzapine (Zyprexa). These medications are considered second-generation neurolepics and antagonize dopamine, serotonin, and other receptors. Quetiapine has relatively less activity at dopamine receptors, resulting in fewer parkinsonian or extrapyramidal symptoms compared to risperidone. Olanzapine tends to have more sedating activity. In general, first generation neuroleptics such as haloperidol (Haldol) and chlorpromazine are avoided. The decision to initiate a neuroleptic agent should be carefully considered by the healthcare provider as these medications have been shown to worsen cognition in the AD population and increase mortality (Vigen, 2011). In addition, studies have demonstrated only modest benefits of these drugs in the setting of side effects such as gait disturbance, somnolence, and extrapyramidal side effects (Lee, 2004) Thus, it is recommended that such medications be used sparingly, particularly when psychotic symptoms fail to respond to behavioral interventions and disrupt the quality of life of the individual or caregivers. In general, risperidone and quetiapine are better tolerated than olanzapine and first generation neuroleptics (Schneider, 2006). There is no role for benzodiazepines or valproic acid in the treatment of neuropsychiatric symptoms in AD (Lonergan, 2009). Sleep disturbances in dementia occur in 46-64% of individuals with dementia, with individuals with AD experiencing frequent nocturnal awakenings and excessive daytime sleepiness (Kesselring, 2001). Sleep disturbances have been associated with wandering behaviors, increased aggressiveness, depression, and decreased functional status, and may increase the likelihood that an individual will be institutionalized (Klein, 1999), (Donaldson, 1998), (Moran, 2005). Thus, the decision to use a sleep aid is a critical intervention that may improve quality of life for both individual and caregiver. Benzodiazepines and typical hypnotics should be avoided as they may worsen amnesia and induce delirium. Trazodone, a serotonin reuptake inhibitor and serotonin 5-HT2A/C antagonist, is the drug of choice for sleep disruption in dementia with initial doses ranging from 25-50 mg, and eventually titrated up to 100 mg. Melatonin has been increasingly used for Lewy body dementia (LBD) based on empirical evidence that the supplement reduces symptoms of REM sleep behavior disorder (Boeve, 2004). There is no evidence showing that melatonin results in the mental status changes that may be seen with benzodiazepines in this population. Finally, a new class of anti-insomnia agents have emerged that antagonize orexin activity (hypothalamic peptide responsible for wakefulness) and in phase III clinical trials, have been shown to improve sleep onset and reduce waking after sleep initiation with relatively minimal side effects (Herring WJ Neurology 2012; American Academy of Neurology Meeting 2014, unpublished). Thus, the orexin receptor antagonists will be another sleep agent alternative to the currently prescribed benzodiazepine-based sleep agents.Responsiveness to the antidepressants, neuroleptics, and/or anti-insomnia agents may be measured either by detailed history or using a formal scale such as the neuropsychiatric index (NPI). For more information about managing AD individuals with behavioral symptoms, refer to MedicationsGuidelines have been developed that are intended to inform the primary care provider about drugs with high likelihoods of negatively impacting cognition or inducing delirium in the geriatric population (American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults; Expert Panel, JAGS, 2012). As a general rule, providers should avoid anticholinergics, benzodiazepines, hypnotics, and narcotics in this population. All of these medications may worsen the amnesia and confusion associated with the underlying neurodegenerative process. Neuroleptics should be avoided in Lewy body dementia and Parkinson’s dementia, as such drugs may worsen motor deficits. The Beers Criteria have been developed for practicing clinicians and are intended for use in all ambulatory and institutional settings of care for populations aged 65 and older in the United States. The criteria is intended to improve the selection of prescription drugs by clinician, evaluate patterns of drug use within populations, educate clinicians on proper drug usage, and evaluate health-outcome, quality of care, cost, and utilization data (American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults; Expert Panel, JAGS, 2012). Refer to ( for an online list.Vitamins and SupplementsThere has been an increasing prevalence of vitamin and supplement use among individual populations with frequent questions regarding the role of over the counter (OTC) medications in the prevention and treatment of AD. Vitamin E, an anti-oxidant, remains one of the most extensively studied vitamin supplements for AD; however, outcomes have varied across studies as well as the continuum of AD. An early study (n=341 subjects) in moderate-severe AD subjects, showed that taking 1000 mg of vitamin E twice daily delayed death, institutionalization, loss of the ability to perform basic activities of daily living, or progression to severe dementia compared to placebo (Sano NEJM 1997). However, the same vitamin E dose in the MCI population failed to reduce progression to AD over a 3-year period (Petersen NEJM 2005). Most recently, a VA multicenter randomized, double-blinded, control study of Vitamin E was published where mild-moderate AD subjects (n=613) received either vitamin E 1000 mg twice daily, memantine 10 mg twice daily, the combination of the two, or placebo (Dysken, 2014). Those individuals receiving vitamin E monotherapy demonstrated relatively decreased decline over a mean follow-up of 2.27 years on functional measures, translating to a 19% decreased annual (or clinically meaningful 6.2 month delay in progression) decline compared to placebo. While there was a modest positive effect on function, there were paradoxical findings such as the investigators failing to show any significant positive effects on cognitive outcomes after adjusting for multiple comparisons; furthermore, subjects receiving both vitamin E and memantine paradoxically had worse outcomes than subjects receiving vitamin E alone. Overall, the drug was found to be safe without significant differences in adverse events or serious adverse events compared to placebo, which contradicted prior findings from a meta-analysis suggesting that vitamin E doses >400 IU/day increase all cause mortality (Miller 2005). Randomized, double-blind, placebo controlled studies of gingko biloba in AD demonstrated no improvement in cognitive performance (Schneider, 2005). Initial studies suggested a role of estrogen supplementation for cognitive issues, yet studies, although unblinded and uncontrolled, have failed to show impact upon cognition (Rigaud, 2003). As a result of the Mediterranean diet, there has been increasing focus on the omega 3 fatty acids, but controlled trials were negative for improvement when administered to AD individuals (Freund-Levi, 2006). Vitamin B supplements have been tried in this population without any proven benefit (Aisen, 2008). In conclusion, there are no vitamins or OTC supplements for which evidence supports a role for routine treatment or prevention of AD.Referral to a Neurologist or GeriatricianThe majority of individuals presenting to the primary care provider should be able to receive quality intervention based on the guidelines discussed in this module. However, the outlined protocol pertains mainly to the typical individuals with AD who represent 60-80% of dementia cases, and the provider may be confronted with either an atypical AD presentation or a non-AD cause of dementia. In such cases, it is recommended that a referral be made to a dementia specialist. For questions related to diagnosis and/or focal neurological findings, a behavioral neurology referral is suggested. In addition to diagnosis, the PCP may have questions relating to medication response or titration schedule. In such cases, either a neurologist or geriatrician may provide insights into the treatment plan. Finally, the geriatrician is a helpful resource for any questions relating to advance planning and end of life care. Longitudinal Follow-Up of the Individual with Alzheimer’s Disease/Dementia Quality MeasuresIn 2012, the interdisciplinary Dementia Measures Work Group (DWG) consisting of the American Academy of Neurology (AAN), the American Geriatrics Society, the American Medical Directors Association, the American Psychiatric Association, and the American Medical Association published quality measures for dementia care based on the physician convened Consortium for Performance Improvement (PCPI) (Odenheimer Neurology, 2013). The included measures were relevant to patients who have been already diagnosed and followed for Alzheimer’s-related illness. Currently, there is no standardized approach to guide clinicians in follow-up measures for Alzheimer’s disease, and these 10 measures represent the “bare essentials” for any individual followed for dementia in a clinical practice. The measures are important not only for ensuring best practice of care, but they also enable participating physicians to receive an incentive payment. All measures except for #9 have been selected by the Patient Quality Reporting System (PQRS), which provides an incentive payment to eligible physicians providing high quality care. Such incentives will be conducive to ensuring a best practice approach among medical providers in primary care, internal medicine, psychiatry, and neurology. The measures are listed below:Measure Title and Description of Final 10 Dementia Measures (measures copyrighted by the American Medical Association, 2012)Measure TitleDescriptionNo. 1: Staging of dementiaPercentage of patients, regardless of age, with a diagnosis of dementia whose severity of dementia was classifiedas mild, moderate, or severe at least once within a 12-month periodNo. 2: Cognitive assessmentPercentage of patients, regardless of age, with a diagnosis of dementia for whom an assessment of cognition is performed and the results are reviewed at least once within a 12-month period. Examples of cognitive assessments include the Montreal Cognitive Assessment (MoCA), Mini Mental Status Exam (MMSE), etc.No. 3: Functional status assessmentPercentage of patients, regardless of age, with a diagnosis of dementia for whom an assessment of functional status is performed and the results are reviewed at least once within a 12-month period. Examples of functional assessment include the functional assessment questionnaire (FAQ),Barthel ADL questionnaire, Lawton IADL scale, etc.No. 4: Neuropsychiatric symptom assessmentPercentage of patients, regardless of age, with a diagnosis of dementia and for whom an assessment of neuropsychiatric symptoms is performed and the results are reviewed at least once in a 12-month period.No. 5: Management of neuropsychiatricsymptomsPercentage of patients, regardless of age, with a diagnosis of dementia who have one or more neuropsychiatricsymptoms who received or were recommended to receive an intervention for neuropsychiatric symptoms within a12-month period. Examples of interventions include pharmacological management with SSRIs and atypical neurolepticsNo. 6: Screening for depressive symptomsPercentage of patients, regardless of age, with a diagnosis of dementia who were screened for depressive symptoms within a 12-month period. Examples of dementia screening tools include the Geriatric Depression Scale (GDS) and Patient Health Questionnaire (PHQ-9)No. 7: Counseling regarding safety concernsPercentage of patients, regardless of age, with a diagnosis of dementia, or their caregiver(s), who were counseled orreferred for counseling regarding safety concerns within a 12-month periodNo. 8: Counseling regarding risks of drivingPercentage of patients, regardless of age, with a diagnosis of dementia, or their caregiver(s), who were counseledregarding the risks of driving and the alternatives to driving at least once within a 12-month periodNo. 9: Palliative care counseling and advance care planningPercentage of patients, regardless of age, with a diagnosis of dementia, or their caregiver(s), who 1) receivedcomprehensive counseling regarding ongoing palliation and symptom management and end-of-life decisions and 2)have an advance care plan or surrogate decision-maker in the medical record or documentation in the medicalrecord that the patient did not wish or was not able to name a surrogate decision-maker or provide an advance careplan within 2 years of initial diagnosis or assumption of careNo. 10: Caregiver education and supportPercentage of patients, regardless of age, with a diagnosis of dementia whose caregiver(s) were provided witheducation on dementia disease management and health behavior changes and were referred to additional resources for support within a 12-month period. Potential resources include organization such as the Alzheimer’s Association and community support groups.For more information regarding dementia quality measures, please refer to and Trial Results for Disease-Modifying Therapies in Alzheimer’s DiseaseAlzheimer’s disease is associated with accumulation of aggregated amyloid-beta (A?) throughout the brain, and thus, this pathological entity has been the target of multiple therapies aimed at Alzheimer’s disease modification and prevention. Over the past decade, multiple clinical trials have investigated the efficacy of biological agents targeting the production, accumulation, and clearance of A?.Drugs Blocking Amyloid ProductionSemagacestat, is a gamma-secretase inhibitor, developed to inhibit the production of CNS A? and was studied in a double-blinded, randomized, placebo-controlled clinical trial over 76 weeks in mild-moderate AD (Doody, 2013). The trial was terminated prior to completion due to higher rates of skin cancers, infections, treatment discontinuations, and serious adverse effects in the treatment group compared to placebo. There were also various laboratory abnormalities affecting white blood cells, immunoglobulins, albumin, total protein, cholesterol, and uric acid/pH. A beta-secretase inhibitor, MK-8931, intended to likewise inhibit accumulation of A? and plaques is currently ongoing in the MCI, mild/moderate AD population. For more information on these trials refer to: and .Drugs Targeting CNS Amyloid Plaque/Abeta Protein Multiple immunotherapies have been developed to target the amyloid beta protein in the soluble (oligomeric) and insoluble (plaque) forms. The intended mechanism of these treatments is binding of CNS amyloid protein followed by transport to the cerebral circulation for clearance. One of the first trials of immunotherapy in AD consisted of an Alzheimer’s vaccine to direct antibodies against amyloid plaques, but the study was terminated after 4 subjects developed meningoencephalitis (Senior Lancet Neurology, 2002). The majority of clinical trials have investigated the effects of specific and non-specific anti-amyloid antibodies in mild-moderate AD. 1. Bapineuzumab, an anti-A? monoclonal antibody, has been studied in two double-blinded, randomized, placebo-controlled, phase 3 trials in mild-to-moderate Alzheimer's disease; one study included 1121 ApoE4 carriers and the other 1331 ApoE4 noncarriers followed over 78 weeks (Salloway, 2014) The medication was administered as an IV infusion every 13 weeks and failed to improve clinical outcomes with respect to cognition and function. 2. AD researchers have hypothesized that the soluble form of A? is the most neurotoxic, which led to trials of solanezumab, an antibody targeting the soluble form of A?. Two phase 3, double-blind trials (Expedition 1 and Expedition 2) randomized 1012 and 1040 subjects, respectively, to receive either solanezumab 400 mg or placebo every 4 weeks for 18 months, eventually finding that the agent failed to improve primary endpoints of cognition and function in the study cohort (Doody, 2014). 3. Intravenous gammaglobulin (IVIG), an agent traditionally used to treat autoimmune conditions such as Guillain-Barre Syndrome and primary immunodeficiency syndrome, has been theorized to include non-specific antibodies targeting both soluble and non-soluble forms of A? in mild-moderate AD. Although phase 2 trials in smaller subject populations showed promising results, a phase 3 randomized, double-blind, placebo-controlled trial failed to meet primary endpoints of improving cognition and function (Relkin 2014). The preliminary findings from clinical trials with anti-amyloid therapy have been disappointing, failing to meet primary endpoints; one hypothesis is that these trials enrolled mild-moderate AD subjects who were too advanced in their disease to show any improvement with anti-amyloid treatment. Consequently, clinical trials have shifted toward testing anti-amyloid agents in the preclinical and mild cognitive impairment (aka prodromal) stages, thus taking the form of Alzheimer’s prevention studies. All of these trials are currently in progress and will require years of longitudinal follow-up before any conclusions are made about the relationship between initiation of anti-amyloid agent and subsequent disease progression. The Alzheimer’s Prevention Initiative (API) Treatment Trial is a clinical trial in the largest kindred carrying the PS1 autosomal dominant mutation for early onset Alzheimer’s Disease and is sponsored by the Banner Institute, the pharmaceutical industry, and the NIH Asymptomatic subjects who are carriers for the PS1 mutation will be randomized to an anti-amyloid agent and followed over 24 months using imaging, cognitive, and spinal fluid endpoints. Individuals who are PS1 carriers are destined to develop Alzheimer’s disease, and the age of disease onset can be compared with that found in the parental carrier to determine drug efficacy. For instance, a drug started in a patient with parental onset at age 40 may be considered effective if the patient does not develop dementia until age 60. For more information about the API, please refer to 2. The Dominantly Inherited Alzheimer’s Network (DIAN) is sponsored by Washington University where carriers of autosomal dominant AD mutations that include PS1, PS2, and APP are followed both clinically and for AD-related biomarkers This cohort represents another unique opportunity to test novel compounds prior to an AD diagnosis. For more information about DIAN, please refer to . The Anti-Amyloid Treatment of Asymptomatic Alzheimer’s Disease (A4) is a clinical trial sponsored by the NIH, industry, and multiple private organizations in patients (n=1000) who have incidental evidence for brain amyloidosis, but no associated cognitive symptoms. Due to the presence of brain amyloidosis, these individuals are thought to be at risk for developing AD, and this trial will randomize patients to medications and follow them over a three year period. All of the above trials will be critical in resolving the dilemma of timing for AD drug interventions as well as testing the amyloid hypothesis in human populations. For more information about the A4 trial please refer to Anti-amyloid treatments are not completely free of risk, and early observations from the bapineuzumab trials have revealed the phenomenon of amyloid associated imaging abnormalities (ARIA) that may present with a clinical syndrome of headache, confusion, and neuropsychiatric and gastrointestinal symptoms accompanied by brain MRI abnormalities of cerebral edema (e.g. ARIA-E) or microhemorrhage (ARIA-H) (Sperling, 2012). This complication was more common in ApoE4 carriers and subjects receiving higher doses of bapineuzumab. ARIA remains a potential side effect associated with any anti-A? treatment, which has prompted pharmaceutical companies to screen for microhemorrhages and lacunar strokes, both of which represent ARIA-related risk factors. Non-Amyloid Based Clinical Trials for ADIntranasal (IN) insulin has emerged as an alternative potential therapeutic agent for mild cognitive impairment and early stage Alzheimer’s disease (AD). In AD, there is a disruption in central nervous system (CNS) insulin signaling, which has been associated with AD pathogenesis, and consequently this disease has been referred to as ”Type III diabetes of the brain” (Steen, J Alzheimers Dis. 2005). Insulin is a large molecule that does not readily cross the blood brain barrier, and intranasal delivery has been found to effectively deliver this drug to the CNS (Renner et al., 2012). AD clinical trials have shown that IN insulin improves verbal retrieval tasks within 15 minutes of administration (Reger et al., 2006) and that memory and functional benefits are sustained when administered over a 4-month period (Craft et al., 2012). Currently, there is a phase II/III multi-site clinical trial through the Alzheimer’s Disease Cooperative Study (ADCS) recruiting AD subjects for the Study of Nasal Insulin to Fight Forgetfulness (SNIFF) trial to better understand the relationship between Alzheimer’s disease, memory performance, and intranasal insulin . For more information about SNIFF and IN insulin , please refer to the website. Case Study Continued:Pharmacological Intervention:Mr. Johnson is started on Donepezil 5 mg daily for 1 month, increasing to 10 mg daily thereafter. The primary provider explains that this medication only provides symptomatic treatment and does not slow the disease process. It is recommended that the patient avoid taking Tylenol PM due to the diphenhydramine’s anticholinergic effects, and he is prescribed trazodone 50 mg at night for insomnia. Since the patient had no evidence for depression by history and score on the Geriatric Depression Scale, there is no role for an antidepressant. Non-Pharmacological InterventionThe primary provider has a Family Meeting where he counsels Mr. Johnson and Dave about healthy lifestyle, safety concerns, maximizing his function, socialization, and ongoing education and support of Mr. Johnson and Dave, his care partner. This is the first time that Dave realizes that he is a “care partner.” Physical activity is the priority, given Mr. Johnson’s diabetes and literature supporting favorable impact of this intervention upon cognition. The patient was recommended to use his home exercise bike for 30 minutes at a time for 3 days weekly. After discussing options for increasing cognitive activity, the patient decides to meet friends to play cards at the senior center twice a week in addition to daily reading. He is also enrolled in a Brain & Body Wellness Program. He is provided a calendar to write down his appointments and activities. At the Brain and Body Wellness program, the health educators stress the importance of a daily routine. The primary provider has numerous safety concerns about Mr. Johnson’s living situation. In the setting of newly diagnosed Alzheimer’s disease, Mr. Johnson has an increased risk for mediation non-adherence. The primary provider recommends that he utilize a pillbox with daily reminders from his son. Dave feels he is able to visit his father once a week and set up two pillboxes indicating the days of the week, one marked “morning” and one marked “evening”; when he makes reminder calls, he can tell his father to take the pills from the appropriate box and indicate the day of the week so that the correct medications are taken. When Dave calls to remind Mr. Johnson about his medication, he will also review the day’s activities with him and write them on a white board on the back of his front door. Mr. Johnson and his son get along well. The primary provider discusses the importance of the care partner; Dave will accompany his father to follow-up appointments so that he will also hear the treatment plan, when the next appointment should be, and symptoms and signs to look for that would indicate a need for a more urgent visit.A home care nurse is arranged to go to the home to assess Mr. Johnson’s home situation for safety, assess if he is able to follow phone instructions from his son accurately, ensure that he is eating regularly, and ensure adequate housekeeping. Mr. Johnson and Dave decide that it might be a good idea to try putting a small table by the front door where he can leave his keys and a stand up glasses case can be placed next to his favorite reading chair. They will put a white board on the back of the front door indicating where the keys and reading glasses might be. If this doesn’t work, they will try another plan.In addition, it is suggested that Dave and his father discuss the possibility of Dave obtaining power of attorney and beginning to manage the patient’s finances. All bills are subsequently placed on autopay. Mr. Johnson has been responsible for his own meals. There have been no problems thus far with forgetting to shut off stove burners. The family is counseled about other options that include prepared meals and microwave meals as well as Meals on Wheels. Mr. Johnson’s primary provider shares Dave’s concerns about Mr. Johnson’s driving safety. Due to symptoms of disorientation in familiar places, the primary provider recommends a formal driving evaluation through occupational therapy. Mr. Johnson is instructed not to drive until this evaluation has been completed. Dave sets up transportation to and from the Senior Center for the card game sessions. They will find out if this senior center has meals, and if so, he may eat a warm lunch with his friends on card game days.The primary provider makes a referral to the Alzheimer’s Association to provide additional education regarding Alzheimer’s disease and information relating to community resources. Mr. Johnson and Dave begin care consultation to learn about the disease, what they might expect as a course of progression, and how to prepare to manage at later stages of the disease. The primary provider sees Mr. Johnson and Dave in follow-up appointments to see how they are coping at home with the new diagnosis. He is tolerating the donepezil without difficulty and adjusting well to his new schedule. His primary provider uses the opportunity to discuss Mr. Johnson’s overall healthcare goals, hopes, and fears about the future. Mr. Johnson would like both of his sons to be his joint health care proxies. He mentions his fears about losing his independence and goal of staying in his own home as long as possible. Given this information, they discuss the importance of identifying a health care proxy and writing an advance directive. They make a plan to see each other in three months for follow-up. Conclusion and Summary DiagramAlthough there is not currently a means to prevent or cure Alzheimer’s disease and related dementias, many quality of life enhancing interventions exist and should be offered to individuals with dementia. A summary diagram of quality interventions for addressing dementia are reflected in the diagram below:1798320155575Interventions for Persons with Dementia00Interventions for Persons with Dementia32385001466850046672563500Detection, Assessment and Care Management Using Dementia as the Organizing Principle for Care(The gateway to all other quality interventions)00Detection, Assessment and Care Management Using Dementia as the Organizing Principle for Care(The gateway to all other quality interventions)3238500533400046672588265Pharmacological00Pharmacological405765088265Non-Pharmacological00Non-Pharmacological25527002159000499110095885001266825958850064579557785Pharmacological Interventions for Memory00Pharmacological Interventions for Memory437007057785Counseling, Education, Support and Planning00Counseling, Education, Support and Planning4057650666750012668256096000441769592075Stimulation, Activity, Maintaining Function00Stimulation, Activity, Maintaining Function2628900138430Referral to Community-Based Organizations for any services not directly provided by the Health Care Provider 00Referral to Community-Based Organizations for any services not directly provided by the Health Care Provider 6457957620Pharmacological Interventions for Mood and Behavior00Pharmacological Interventions for Mood and Behavior132397513970000446532018415Safety00Safety64579547625Pharmacological Interventions for Comorbid Depression00Pharmacological Interventions for Comorbid Depression447421064135Environment00Environment446532081280Advanced Care Planning00Advanced Care PlanningModule VIII: Questions for ReviewAn 82-year-old man is diagnosed with amnestic Mild Cognitive Impairment (MCI) by his primary care provider. Which of the following is true about MCI?Individuals with MCI have a 10-15% annual risk of progression to dementiaDonepezil (Aricept) can prevent the progression of mild cognitive impairment to dementia. All individuals with MCI progress to dementia.Cognitive training has not been shown to prevent the progression of MCI to dementia.Which of the following statements about the assessment of a cognitively impaired driver is true?Most older adults with mild dementia can no longer pass an on-the-road driving test.Mental status testing (i.e. Mini Mental Status Examination) scores are highly correlated with unsafe driving.The diagnosis of dementia should prompt the clinician to restrict driving privileges.A caregiver report of driving concerns is not correlated with reduced safe driving capacity.Poor performance on the Trail Making B test is associated with motor vehicle crashes.Mr. A is an 80-year-old man with a history of diabetes, hypertension, depression, and moderately severe Alzheimer’s disease. He comes in today for a general health maintenance visit. His blood pressure has been under good control. He lives at home with his wife, who manages the household and cooks all meals. Mrs. A has noticed that her husband has been losing weight and seems to have very little appetite. The patient acknowledges that his stools are loose and that he often has low-grade abdominal pain. His current medications include: quetiapine 25 mg po bid, aspirin 81 mg daily, metoprolol 25 mg by mouth twice daily, donepezil 10 mg po daily, simvastatin 40 mg po nightly, mirtazapine 15 mg po nightly, and hydrochlorothiazide 25 mg by mouth daily. Which of the following medications is likely causing his abdominal pain?QuetiapineDonepezilSimvastatinMirtazapineHydrochlorothiazideCholinesterase inhibitors may worsen cognitive symptoms in which of the following conditions?Alzheimer’s diseaseLewy body dementiaFrontotemporal dementiaDementia associated with cerebrovascular diseaseMild Cognitive Impairment You are seeing an 80-year-old woman with a history of Alzheimer’s disease in the ambulatory care setting. She is brought in at the request of her children due to increasing behavioral disturbance at her assisted living facility. She has been calling out for someone to help her (repeatedly), but when a home care aide assesses her, she has no particular concerns or problems. She has also been hitting/grabbing/spitting at her home care aide during bath time and personal cares. On physical examination, she is calm and pleasant. Vital signs, ENT, cardiovascular, abdominal, and pulmonary examination are normal. Musculoskeletal examination does reveal pain in bilateral shoulders during passive and active range of motion. Her medications include donepezil 10 mg daily, citalopram 40 mg daily, aspirin 81 mg daily, and lisinopril 10 mg daily. Her family is distraught about her behavioral symptoms as she is at risk of being asked to leave the assisted living facility. Which of the following is the most appropriate next step?Prescribe quetiapine 12.5 mg prior to bath time.Prescribe lorazepam 0.5 mg prior to bath time and prn agitation.Recommend transition to the nursing home (skilled care) setting.Optimize her antidepressant medication by increasing Celexa to 60 mg po daily.Interview other caregivers about the bath time routine and environmental triggers. 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