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Work-up of the Forgetful Patient

December 2004

Authors: Tim Lewis M.D.

Core Competencies: Patient Care, Medical Knowledge

Learning Objectives: After reading this AME, learners should be able to:

1. List five differential diagnoses for adult-onset cognitive impairment

2. Describe an effective work-up for a forgetful patient

3. Identify abnormal results on the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT)

4. Describe a simplified algorithm for the differential diagnosis of dementia

5. List two indications for neuropsychological testing

Key Points

➢ Age-associated cognitive decline ("normal aging"), mild cognitive impairment and dementia form a continuum of cognitive dysfunction

➢ Along with cognitive history and detailed neuro exam, validated tools such as MMSE and Clock Drawing Test (CDT) are useful in diagnosing cognitive decline

➢ Only a few simple standard tests are recommended for evaluating suspected dementia; CSF evaluation and neuro-imaging are usually reserved for certain specific clinical situations

Introduction: The causes of cognitive decline in the elderly range from benign conditions such as age associated memory loss to serious conditions such as delirium and dementia. All these conditions produce memory problems.

Differential Diagnosis for Adult Memory Loss:

Several conditions can cause memory decline in adults (see Table 1). Age-associated cognitive decline (AACD) describes the subjective and objective memory problems associated with normal aging (e.g., trouble remembering names or appointments) with preservation of other aspects of functional status. AACD is distinct from the condition of mild cognitive impairment (MCI) that is an intermediate transitional stage between AACD and dementia. Not all people with MCI progress to dementia; studies have confirmed that 6% to 25% of patients with MCI convert to dementia per year.

Table 1: Differential diagnosis of adult-onset cognitive impairment

|Condition |Distinguishing Features |

|Age associated memory impairment |Age >50, memory complaints prominent, performance < 1 SD from the mean on tests normed with young |

| |adults, information retrieval slowed; functional independence preserved, other cognitive functions |

| |intact. |

|Mild cognitive impairment |Age >50, memory complaints prominent, performance < 1.5 SD from the mean on tests normed with young |

| |adults, information retrieval slowed; functional independence preserved, other cognitive functions |

| |intact. |

|Dementia |Progressive decline, global cognitive impairment with learning and memory deficits (recent > remote),|

| |aphasia, apraxia, agnosia, executive dysfunction; patients tend to minimize deficits. |

|Delirium |Sudden onset and fluctuating course with inattention, disorganized thinking, and altered level of |

| |awareness; impairment reversible. |

|Major Depressive Disorder with |Memory and concentration complaints prominent; aphasia absent, apathy or irritability present; |

|cognitive impairment |cooperation with testing difficult, risk of subsequent dementia elevated. |

Source: Adapted from Cassel, 2003:1080.

Figure 1. Simplified Algorithm for the Differential Diagnosis of Dementia

|Step 1: Insidious onset with smooth decline and motor function minimally impaired? |Yes -> Alzheimer’s |

| |No -> Step 2 |

|Step 2: Abrupt onset or fluctuating course, little if any psychosis? |Yes -> Vascular |

|History of stroke or significant ischemic brain injury on CATscan or MRI? |Dementia |

| |No -> Step 3 |

|Step 3: Marked fluctuation in cognitive impairment, falls, hallucinations prominent, signs of |Yes -> Lewy body disease |

|Parkinson’s syndrome evident? | |

Source: Adapted from Cassel, 2003: 1081.

Diagnostic Assessment of the Forgetful Patient

Effective assessment of the forgetful patient requires careful history taking, physical examination, mental status testing, and selective laboratory and radiographic tests. Three general areas need to be evaluated: cognition, functional status, and behavioral problems.

Step 1: Take an effective cognitive history focusing on these issues:

1. Has there been a true change in patient’s cognitive status and if so, what is the nature of that change?

1. What were the onset, nature, and progression of any observed changes?

2. What were the initial symptoms?

3. What changes have the family members or equivalent caregivers observed?

4. After onset, how long did it take the patient to reach her present level of function?

5. Have the observed cognitive changes been severe enough to degrade the individual’s well-being and social function?

Clinical Pearl: Family members may believe that a disorder came on suddenly when it did not. Explore the context in which the patient’s cognitive changes were first noted. If the family suddenly became aware of the patient’s cognitive decline during an unusual external event such as a trip to an unfamiliar place or a hospitalization, investigate whether any symptoms of cognitive change preceded the event.

Step 2: Perform a general medical examination, paying special attention to the patient’s speech, memory, and neurologic exam. Subjective assessment of the patient’s memory and language function during the routine examination can reveal important diagnostic clues. Study the patient as they converse about a current event. Are they familiar with the event in question, and if so, is their familiarity more than general? Observe their speech for fluency and comprehension. Observe the patient’s gait for diagnostic clues.

Step 3: Perform a validated mental status test. Tests such as the MMSE and CDT help identify persons with cognitive dysfunction. When repeated over time, mental status testing also serves to establish baseline cognitive performance against which future performance can be compared. Interpretation of the MMSE and CDT is presented below. Pre-printed MMSE forms are available.

MMSE: MMSE scores range from 0 to 30, with scores greater than 26 generally indicating normal cognitive function. A cut-off score of 23 or lower generally indicates cognitive dysfunction, however, interpretation of the MMSE score requires consideration of the patient’s educational level (see Table 3).

Table 3: Cutoffs for Abnormal MMSE Scores based on Educational Level

|Years of Education |Cutoff Score (at or below) |

|8 or fewer |17 |

|8 to 15 |23 |

|16 or more |27 |

Source: Cassel, 2003: 206-207.

Clock Drawing Test: The CDT is a useful measure of cognitive function that requires less than 5 minutes to complete. Instruct the patient to draw a clock face with all the numbers and hands and then to state the time as drawn. A score less than 4 is considered impaired. The CDT’s diagnostic sensitivity for cognitive dysfunction is improved with these instructions: “Set the hands to ten minutes after eleven” (Freedman, 1994). Scores on the CDT range from 0 to 6 and are derived according to 4 rules:

|Scoring Rules for CDT |Associated Points |

|12 must appear on top |3 points |

|12 numbers must be present |1 point |

|Must be 2 distinguishable hands |1 point |

|Time must be identified correctly |1 point |

Source: Stahelin HB:1997.

Step 4: Depending on the circumstances and clinical information, order laboratory and/or neuro-imaging studies to help exclude other possible causes of chronic cognitive impairment. Items 1-5 are obtained in most instances for patients with suspected dementia. Reserve brain-imaging studies for patients that have a history suggestive of a mass, focal neurological signs, or dementia of brief duration or rapid progression.

Laboratory and Radiographic Work-up of Chronic Cognitive Impairment

1. Complete Blood Count

2. Serum electrolytes

3. Biochemical screening (calcium, renal panel, LFTs)

4. Serum vitamin B12 level

5. Thyroid function tests

6. Urinalysis

7. Toxicology screen

8. Arterial blood gases

9. Serologic tests for syphilis

10. Human immunodeficiency (HIV) antibodies

11. Chest films

12. Lumbar puncture / CSFanalysis

13. Computerized tomography or magnetic resonance imaging brain

Detailed Neuropsychological Testing: Referral for detailed cognitive testing is indicated when there is a discordance between the history and findings on office-based mental status tests (i.e.,“things just don’t add up”) or when subtle cognitive dysfunction is suspected in intellectually gifted individuals or those with higher educational attainment.

Questions

1. You receive a note in clinic that the daughter of one of your 84 year old patients called to say she’s concerned her father is becoming “forgetful”. The observed change is not acute. You are scheduled to see the patient next week. Your next best step is to:

A. Refer patient for detailed neuropsychological testing.

A. Arrange for MRI/MRA brain, then refer patient to neurology.

B. Refer patient to the Alzheimer’s Association.

C. Call the daughter to obtain more relevant history and plan to administer the MMSE and CDT to the patient next week in the office.

D. Refer patient to neurosurgeon for brain biopsy.

2. A 70 year old retired chemical engineer presents with the complaint “My wife says I have a memory problem”. He admits to some memory problems but attributes this to normal aging. He is unable to give specific examples. He is still driving, socializing with friends and generally leads an active life. However, on a recent hospital admission he became disoriented and was found wandering the halls on several occasions. His wife says he is having a more difficult time completing tasks such as balancing the check book. He also keeps forgetting his grandchildren’s names. His clock drawing test was perfect. He scored a 28/30 on the MMSE, missing two of the memory items. Neurological exam is nonfocal. What should be done for this patient?

A. Reassure the patient he has only age associated memory decline.

A. Tell the patient he has Alzheimer’s disease.

B. Refer for detailed neuropsychological testing.

C. Order MRI/MRA brain

3. A 60 year old male with HTN presents to the office complaining of “forgetting things.” He has misplaced his keys on several occasions. At a retirement party last week he went to introduce his wife to a coworker and forgot the coworker’s name. On occasion he can’t find his car in parking lots. He is still managing the household finances effectively. He and his wife have recently returned from a vacation that he planned. He did most of the driving, without problems. His wife has not noticed any behavioral problems or memory problems. He had 12 years of education; MMSE score is 27/30. He most likely has:

A. Age associated memory impairment

B. Alzheimer’s

C. Vascular dementia

D. Lewy body disorder

Answers

1. Answer D, Call the daughter to obtain more relevant history and plan to administer the MMSE and CDT to the patient next week in the office. The initial evaluation of a forgetful patient should include a cognitive history preferably taken from the patient and a reliable collateral historian, a focused physical examination, and completion of validated mental status tests such as the MMSE and CDT. Neuro-imaging studies are indicated only in select clinical circumstances, such as when there are focal neurologic signs or clinical evidence of a brain mass. Referral of a forgetful patient and his/her family for community support services such as the Alzheimer’s Association is appropriate after a diagnosis of dementia has been made. Detailed neuropsychological testing is generally not indicated in the initial work-up of a forgetful patient, but may be considered in certain clinical situations, such as when the findings on history and office-based mental status testing are discordant.

2. Answer C, Refer for detailed neuropsychological testing. There is insufficient evidence to render a diagnosis of Alzheimer’s disease, however, the presence of functional impairments goes against a benign diagnosis such as age associated memory decline. Given this patient’s higher educational attainment, the MMSE and CDT may be “too easy” for this patient and thus relatively insensitive measures of decrements in his cognitive function. The history of recent confusion, memory problems, and difficulty with checkbook balancing for a patient with his educational background should raise the suspicion that the patient could in fact have an early dementia, however, the history and available test findings are not conclusive. Neuropsychological testing may clarify the extent of his current cognitive deficits and may also serve as a reference against which to detect subsequent cognitive decline. There is nothing in the patient’s history or exam findings to suggest stroke, brain mass, subdural hematoma, or any other condition for which neuro-imaging would be indicated.

3. Answer A, Age associated memory impairment. The history and assessment findings in this case are consistent with age associated memory impairment. His MMSE score of 27 is normal for his educational level (i.e., MMSE for someone with 8 to 15 years of education is abnormal if it is 23 or less). His history is notable for the absence of significant functional impairments, thus dementia is ruled out. The memory lapses cited are within the scope of normal aging.

Acknowledgement:  The authors of this AME wish to thank Gregg Warshaw,

Professor of Geriatric Medicine, for contributing content expertise

concerning the diagnostic evaluation of the forgetful patient.

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Clock Drawing Test Examples

These patients were told to set the clock at 1:45



This patient was told to set the clock at 10:30



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