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Continuum (Minneap Minn). 2016 April; 22(2 Dementia): 679–688.
PMCID: PMC5390932

Patient Management Problem—Preferred Responses

Following are the preferred responses for the Patient Management Problem in this Continuum issue. The case, questions, and answer options are repeated, and the preferred response is given, followed by an explanation and a reference with which you may seek more specific information. You are encouraged to review the responses and explanations carefully to evaluate your general understanding of the material. The comment and references included with each question are intended to encourage independent study.

To obtain CME credits for this activity, subscribers must complete this Patient Management Problem online at www.aan.com/continuum/cme. Upon completion of the Patient Management Problem, participants may earn up to 2 AMA PRA Category 1 CreditsTM. Participants have up to 3 years from the date of publication to earn CME credits. No CME will be awarded for this issue after April 30, 2019.

Learning Objectives

Upon completion of this activity, the participant will be able to:

  • Discuss the differential diagnosis of patients presenting with progressive cognitive impairment
  • Discuss the diagnosis and management of cognitive and behavioral symptoms in patients with Alzheimer disease

Case

A 57-year-old man is referred by his family doctor for memory deficits. He reports some forgetfulness, such as forgetting where he put his keys or trouble recalling people’s names, but generally feels his memory is “not too bad for a guy [his] age.” During the interview, the patient’s wife attempts to contradict his answers to some of the physician’s questions, which appears to agitate the patient. Following the interview and examination of the patient, the patient’s family is interviewed separately to discuss any concerns they may have. The patient’s spouse then reports that the family first noticed changes in the patient’s memory beginning 3 years ago. He began to miss dental appointments, forgot to pick up their daughter from swim practice, and got lost on a few occasions when driving in their home town. The changes started gradually but have progressed. They now find he repeats questions and stories multiple times within a few minutes, is confused when attempting to complete projects at home or pay the bills, and has accused family members of stealing his wallet. He has not experienced any hallucinations. He was recently laid off from his job as a welder. He drives and has had no accidents or tickets in the past 3 years. He smokes 10 cigarettes and drinks two beers per day. He has no significant past medical history and takes no medications.

1. Given the patient’s history, what is the most likely working diagnosis?

  1. Alzheimer disease
  2. autoimmune encephalopathy
  3. dementia with Lewy bodies
  4. frontotemporal dementia
  5. vascular cognitive impairment

The preferred response is A (Alzheimer disease). The patient’s initial forgetfulness as described by the family is suggestive of amnestic mild cognitive impairment. Over time, his symptoms progressed to indicate that his memory impairments and deficits in executive functioning (difficulty completing projects) and navigation impacted his daily functioning, consistent with progression to dementia. The gradual onset and progression of deficits in short-term memory and navigation are most commonly associated with Alzheimer disease.1 Repetitiousness, misplacing objects, and accusing others of stealing one’s possessions when they are misplaced around the home are all hallmark symptoms of memory deficits in Alzheimer disease. Vascular cognitive impairment would typically be associated with a stepwise decline. Dementia with Lewy bodies may present with alterations in level of arousal, parkinsonism, and visual hallucinations. While patients with frontotemporal dementia may have memory deficits, this is not typically the predominant feature, and navigational deficits in frontotemporal dementia are rare.

1. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7(3):263–269. doi:10.1016/j.jalz.2011.03.005.

A working diagnosis of Alzheimer disease is considered. The patient’s neurologic examination shows full extraocular movements with normal vertical saccades, normal axial and appendicular tone, no tremor, no bradykinesia, normal ideomotor praxis and stereognosis bilaterally, and normal gait. On the Mini-Mental State Examination (MMSE), he scores 22 out of 30, losing points for orientation, recall, and attention.

2. In addition to neuroimaging, which of the following is the next appropriate step in the workup of this patient?

  1. amyloid positron emission tomography (PET) scan
  2. EEG
  3. further cognitive testing and assessment of function
  4. lumbar puncture
  5. polysomnogram

The preferred response is C (further cognitive testing and assessment of function). The MMSE is a screening test for cognitive impairment. More detailed objective measurement of cognitive deficits and activities of daily living is necessary to confirm the deficits reported by the patient or family members and to aid in staging the severity of deficits.1 Sleep apnea may result in excessive daytime somnolence, contributing to cognitive deficits; thus, taking the patient’s history should include screening questions for sleep apnea and, if present, consideration of referral for a formal sleep study. Lumbar puncture and EEG are indicated in the workup of a rapidly progressive dementia. While the patient’s presentation is typical for Alzheimer disease, CSF amyloid-β (Aβ) and tau measurements could be considered given the early age of onset (younger than 65 years of age), although CSF analysis may be most helpful in diagnostically challenging cases (ie, patients presenting with mixed features of frontotemporal dementia and Alzheimer disease). Similarly, amyloid PET may be useful in differentiating Alzheimer disease from frontotemporal dementia and may be considered in patients with early-onset disease if the results are expected to change disease management. In this patient, although the age of onset was before age 65 years, the patient’s features and course were typical for Alzheimer disease and, thus, lumbar puncture and amyloid PET imaging were not indicated.2

1. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143–1153. doi:10.1212/WNL.56.9.1143.

2. Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J 2012;15(4):120–126. doi:10.5770/cgj.15.49.

3. On further cognitive testing, a patient with mild Alzheimer disease would be expected to demonstrate which of the following patterns of performance?

  1. impaired episodic memory, mild anomia, mild deficits on executive function tests
  2. impaired executive functions, impaired letter fluency worse than category fluency, impaired retrieval
  3. impaired grammar, deficits in comprehension, impaired calculations
  4. impaired recall of recently learned information, grammar deficits, preserved visuospatial abilities
  5. impaired single-word comprehension, preserved fluency, preserved visuospatial skills

The preferred response is A (impaired episodic memory, mild anomia, mild deficits on executive function tests). Patients with Alzheimer disease demonstrate early deficits in episodic memory, often manifested by impaired recall of recently learned information.1 In the early stages of the disease, encoding and consolidation are impaired while retrieval is relatively preserved. Executive function tasks are often impaired early on in Alzheimer disease, and some patients may demonstrate mild anomia. Category fluency is typically impaired while letter fluency may be preserved. Deficits on visuospatial tasks are common. Grammar is typically preserved in patients with Alzheimer disease, including in the logopenic aphasia variant of primary progressive aphasia typically associated with Alzheimer disease pathology.1 Single-word comprehension is preserved in Alzheimer disease, but is a classic deficit in semantic dementia.

1. Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harb Perspect Med 2012;2(4):a006171. doi:10.1101/cshperspect.a006171.

The Alzheimer’s Disease Assessment Scale—Cognitive Subscale (ADAS-Cog) is administered. The patient shows difficulties learning a list of words, with just 5 out of 10 recalled immediately after three trials and, following a delay, he recalls only 2 out of 10 words. He is able to copy a circle but makes mistakes when drawing a cube. He follows all commands and names only 8 out of 12 items correctly. He is oriented to the year but not the month or day of the week.

4. Which of the following additional measures or historical features would be most important to obtain in this patient?

  1. history of exposure to ticks
  2. retrieval of patient’s driving record from the department of motor vehicles/ministry of transportation
  3. screening for depression and other neuropsychiatric symptoms
  4. screening for risk factors for syphilis
  5. vaccination history

The preferred response is C (screening for depression and other neuropsychiatric symptoms). Assessment of a patient with cognitive complaints should include screening for depression and other neuropsychiatric symptoms, which can be associated with deficits in attention, concentration, and working memory.1 Patients with impairments in frontal lobe functions or memory may have impaired insight or recollection of these symptoms; thus, collection of collateral history from a knowledgeable informant is essential. A review of neuropsychiatric symptoms including agitation, wandering, impulsivity, delusions, hallucinations, anxiety, depression, and insomnia should be reviewed at each visit as these symptoms may inform the diagnosis and often impact quality of life for patients and caregivers and thus require management when possible.2 Delusions of theft and infidelity are common in patients with Alzheimer disease, and anxiety and depression are common in patients with Alzheimer disease and dementia with Lewy bodies. Additionally, screening for safety-related behaviors such as wandering, use of the stove, presence of guns, or use of other dangerous equipment or tools in the home is indicated at each visit. Physicians are not required to obtain official driving records but confirmation of the patients’ driving history within the past 5 years, including difficulties with navigation, accidents, or tickets from a reliable informant, is critical.

1. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143–1153. doi:10.1212/WNL.56.9.1143.

2. Hogan DB, Bailey P, Black S, et al. Diagnosis and treatment of dementia: 4. Approach to management of mild to moderate dementia. CMAJ 2008;179(8):787–793. doi:10.1503/cmaj.070803.

The patient’s family doctor has recently checked his complete blood cell count, electrolytes including magnesium, calcium, and phosphorus, liver function tests, and vitamin B12 levels, which were within normal limits.

5. Additional routine laboratory workup should include which of the following blood tests?

  1. antinuclear antibody
  2. C-reactive protein
  3. erythrocyte sedimentation rate
  4. thyroid-stimulating hormone (TSH)
  5. venereal disease research laboratory (VDRL)

The preferred response is D (thyroid-stimulating hormone [TSH]). Patients presenting with cognitive complaints should be screened with a complete blood cell count, electrolytes including calcium levels, liver function tests, TSH, and vitamin B12 level to rule out these reversible causes of dementia. VDRL, human immunodeficiency virus (HIV), or other infection screening is indicated only for patients with risk factors.1 Inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein, or antinuclear antibody would be indicated for patients with a history suggestive of a rapidly progressive dementia or other autoimmune disease risk factors or symptoms.2

1. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143–1153. doi:10.1212/WNL.56.9.1143.

2. Geschwind MD. Rapidly progressive dementia: prion diseases and other rapid dementias. Continuum (Minneap Minn) 2010;16(2 Dementia):31–56. doi:10.1212/01.CON.0000368211.79211.4c.

6. Which is the most appropriate imaging test to order at this time?

  1. amyloid PET
  2. CT angiography of head and neck
  3. CT scan of the brain
  4. fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain
  5. MRI scan of the brain

The preferred answer is E (MRI scan of the brain). A structural imaging study is indicated for patients presenting with cognitive deficits to rule out a structural etiology such as a tumor or normal pressure hydrocephalus. MRI is preferred, as white matter lesions and microhemorrhages such as those seen in cerebral amyloid angiopathy, either of which may contribute to cognitive impairment, may be better visualized on MRI.1,2 For patients unable to undergo MRI, CT imaging is a reasonable substitute. FDG-PET and amyloid PET may help specifically to differentiate Alzheimer disease from frontotemporal dementia but are not routinely indicated in the diagnostic workup of patients presenting with cognitive impairment. There is no specific role for vascular imaging in the initial workup of cognitive impairment.

1. Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178(7):825–836. doi:10.1503/cmaj.070798.

2. Harper L, Barkhof F, Scheltens P, et al. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry 2014;85(6):692–698. doi:10.1136/jnnp-2013-306285.

The patient’s laboratory blood work returns normal. The MRI demonstrates bilateral hippocampal atrophy and widening of the sylvian fissures, but no other structural lesions. At a follow-up visit, a diagnosis of probable Alzheimer disease is made and discussed with the patient and caregiver.

7. Which of the following treatments should be initiated at this time?

  1. a cholinesterase inhibitor
  2. coconut oil
  3. ginkgo biloba
  4. memantine
  5. vitamin E

The preferred answer is A (a cholinesterase inhibitor). The cholinesterase inhibitors donepezil, galantamine, and rivastigmine are typically indicated for symptomatic treatment of cognitive impairment in mild to moderate Alzheimer disease. Donepezil and the high-dose rivastigmine patch (13.3 mg every 24 hours) are approved by the US Food and Drug Administration (FDA) for use in severe Alzheimer disease. These medications have been associated with a modest improvement in cognition in a portion of patients with Alzheimer disease. While there have been case reports published suggesting benefit of coconut oil in Alzheimer disease, controlled trials are ongoing, and there is insufficient evidence to date to recommend this as therapy. Trials of vitamin E and ginkgo biloba have failed to show a benefit in Alzheimer disease. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has also been approved for use in moderate to severe Alzheimer disease. While memantine appears safe as monotherapy or when added to a cholinesterase inhibitor, evidence of a modest benefit is equivocal in moderate to severe Alzheimer disease1 and meta-analysis suggests there is not a benefit in patients with mild Alzheimer disease.2 Thus, some recent guidelines support the use of memantine in moderate and severe Alzheimer disease, and others suggest there is insufficient evidence to support or refute use of memantine in moderate to severe Alzheimer disease.3

1. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 2012;366(10):893–903. doi:10.1056/NEJMoa1106668.

2. Schneider LS, Dagerman KS, Higgins JP, McShane R. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol 2011;68(8):991–998. doi:10.1001/archneurol.2011.69.

3. Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J 2012;15(4):120–126. doi:10.5770/cgj.15.49.

8. When counseling the patient and family prior to prescribing a cholinesterase inhibitor, which of the following should be discussed as the most common side effect?

  1. bradycardia
  2. gastrointestinal symptoms
  3. liver abnormalities
  4. rash
  5. seizures

The preferred answer is B (gastrointestinal symptoms). On average, the cholinesterase inhibitors are associated with an approximate 20% incidence of gastrointestinal side effects including nausea, with approximately 5% of patients experiencing more severe nausea, vomiting, or diarrhea.1 A less common but more serious adverse reaction to the cholinesterase inhibitors is bradycardia, which can be life threatening.2 Thus, measurement of pulse and assessment of cardiac symptoms is indicated before initiation.Less common and less serious side effects of this class include vivid dreams, including nightmares, and persistent rhinorrhea. Other possible side effects due to cholinergic effects include seizures, worsening of urinary obstruction in patients with prostatic hyperplasia or urinary outlet obstruction, or exacerbation of asthma. As many patients will not show a favorable response to this class of medications, response to treatment should be assessed after a few months.3 If no favorable response is observed, discontinuation is recommended, and a trial of an alternate agent in the class can be considered.

1. Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1154–1166. doi:10.1212/WNL.56.9.1154.

2. Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009;169(9):867–873. doi:10.1001/archinternmed.2009.43.

3. Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J 2012;15(4):120–126. doi:10.5770/cgj.15.49.

Prior to completion of the follow-up visit, driving privileges are discussed with the patient and his family in light of a diagnosis of Alzheimer disease and his performance on the cognitive testing.

9. Which of the following factors best predicts a patient’s driving abilities?

  1. caregiver’s rating of patient’s driving as safe
  2. history of crashes in the past 5 years
  3. lack of reduction of patient’s driving mileage or situational avoidance
  4. neuropsychological testing scores
  5. patient’s self-reported driving abilities

The preferred answer is B (history of crashes in the past 5 years). There is level C evidence that a history of crashes in the past 5 years or traffic citations in the past 3 years are associated with an increased risk of future crashes.1 Caregivers’ ratings of patients’ driving as unsafe is a predictor of unsafe driving, but the opposite, caregivers’ judgment of patients’ driving as safe, has not been found to be reliably associated with safe driving performance. A reduction in driving mileage or situational avoidance has been associated with increased risk of unsafe driving, but a lack of reduction or avoidance has not. The presence of impulsive or aggressive personality characteristics has been associated with unsafe driving risk. While neuropsychological testing generally has not been highly predictive of driving risk, an MMSE score or 24 or less may be somewhat useful in identifying patients possibly at increased risk of unsafe driving.1 Studies of driving in patients with dementia have tended to collapse the groups across all causes of dementia and, thus, have weighted the results toward patients with Alzheimer disease. The few studies conducted in patients with frontotemporal dementia consistently indicate that the risk of unsafe driving is high even in early stages of disease, while there are no studies specifically in patients with dementia with Lewy bodies.2,3

1. Iverson DJ, Gronseth GS, Reger MA, et al. Practice parameter update: evaluation and management of driving risk in dementia: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74(16):1316–1324. doi:10.1212/WNL.0b013e3181da3b0f.

2. de Simone V, Kaplan L, Patronas N, et al. Driving abilities in frontotemporal dementia patients. Dement Geriatr Cogn Disord 2007;23(1):1–7. doi:10.1159/000096317.

3. Fujito R, Kamimura N, Ikeda M, et al. Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer’s disease [published online ahead of print March 3, 2015]. Psychogeriatrics. doi:10.1111/psyg.12115.

At the next visit the patient’s spouse and adult children ask if his illness could be hereditary and if they and the patient can be tested for genetic risks. The patient’s father had “dementia” with onset around age 55. The family recalls that he became angry and stopped recognizing family members. He went into a nursing home and died around age 70. A paternal uncle had depression and also developed dementia in his late fifties. The patient’s mother lived to age 86 and died of a myocardial infarction.

10. To address the family’s question about heritability, what is the next appropriate step?

  1. reassurance that familial early-onset Alzheimer disease is rare
  2. referral of the patient and family for genetic counseling
  3. screening of the family members for early-onset Alzheimer disease gene mutations
  4. testing for apolipoprotein E (APOE) genotype
  5. testing of the patient for presenilin 1 (PSEN1), amyloid-β precursor protein (APP), and presenilin 2 (PSEN2) mutations

The preferred answer is B (referral of the patient and family for genetic counseling). A referral for genetic counseling is recommended for symptomatic testing for patients with possible familial early-onset Alzheimer disease and is essential for individuals considering predictive testing. The patient’s presentation with probable Alzheimer disease prior to age 60 and likely history of early-onset dementia in his father raise the possibility of an autosomal dominant early-onset familial Alzheimer disease. Autosomal dominant mutations are a rare cause of Alzheimer disease overall; however, in kindreds with three family members across three generations affected before age 60, the probability of identifying an autosomal mutation is approximately 86%.1 The most common genetic mutation associated with familial early-onset Alzheimer disease is PSEN1, followed by mutations in APP. APOE4 status is associated with a higher risk of developing Alzheimer disease but the presence is not diagnostic and, thus, symptomatic and predictive genetic testing of APOE genotype is not recommended.

1. Loy CT, Schofield PR, Turner AM, Kwok JB. Genetics of dementia. Lancet 2014;383(9919):828–840. doi:10.1016/S0140-6736(13)60630-3.

After genetic counseling, the patient elects to undergo genetic testing and is found to carry an Alzheimer disease–causing mutation in the PSEN1 gene. The patient’s adult children, who are asymptomatic, inquire about the possibility of genetic testing for themselves. A referral is made for genetic counseling for all interested asymptomatic family members to further consider the potential consequences of genetic testing. One year later the patient is unable to operate appliances at home, prepare meals, or manage his medications without assistance. He can dress and feed himself independently. His MMSE score in clinic is 16 out of 30.

11. The patient’s disease severity is now best classified as which of the following?

  1. mild
  2. moderate
  3. prodromal
  4. severe
  5. terminal

The preferred response is B (moderate). Staging of dementia severity can be accomplished through clinical interview of activities of daily living, through standardized measures assessing functional activities such as the Clinical Dementia Rating scale or the Dementia Severity Rating Scale, or estimated through cognitive screens such as the MMSE. Patients in moderate stages of Alzheimer disease have difficulties with instrumental activities of daily living (eg, managing the finances and shopping) but are able to perform basic activities of daily living (eg, dressing, feeding, and toileting). MMSE ratings between 11 and 20 are generally considered to be associated with moderate-stage Alzheimer disease. Assessment of disease severity at onset and at least annually is considered a best practice to guide patient management and council family members and caregivers on prognosis and anticipated course of symptoms.1

1. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1143–1153. doi:10.1212/WNL.56.9.1143.

At the next visit 6 months later, the patient’s spouse appears rather distressed and notes that he has become more dependent and requires near complete supervision at home due to wandering tendencies. She is tearful and reports poor sleep as she is fearful he may fall or wander when he awakens in the middle of the night.

12. Which of the following represent important management approaches for these behaviors?

  1. prescription of an antidepressant for the caregiver
  2. prescription of a sleep aid for the caregiver
  3. prescription of a sleep medication for the patient
  4. prescription of quetiapine for wandering behavior
  5. referral of the patient to a day program

The preferred response is E (referral of the patient to a day program). Caregivers of patients with dementia are at high risk of depression, caregiver burnout, and medical problems. As the patient’s dementia advances, maintaining options for caregiver respite is critical for the well-being of the patient and caregiver. Referrals to local day care programs for patients with dementia, Alzheimer society for social work and caregiver support groups, and other community organizations for care relief are essential for caregivers.1 Prescription sleep aids are associated with only a mean increase of 15 minutes of increased sleep per night and are associated with an increased risk of hip fractures and pneumonia in elderly patients.2 Neuroleptic medications may be required for aggression or psychosis in dementia but are typically not effective for wandering behaviors, which are better treated with nonpharmacologic strategies including redirection and safety door locks or alarms. Neuroleptic medications are associated with increased cardiovascular morbidity and mortality and cerebrovascular events in patients with dementia.

1. Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56(9):1154–1166. doi:10.1212/WNL.56.9.1154.

2. McMillan JM, Aitken E, Holroyd-Leduc JM. Management of insomnia and long-term use of sedative-hypnotic drugs in older patients. CMAJ 2013;185(17):1499–1505. doi:10.1503/cmaj.130025.


Articles from Continuum : Lifelong Learning in Neurology are provided here courtesy of American Academy of Neurology