Pathophysiology
This extracellular protein forms plaques in the brain and is strongly associated with the development of Alzheimer disease
Beta amyloid
Gradual onset and progression
Primarily short-term memory loss
Motor symptoms rare
Global atrophy on head CT
Alzheimer disease
A 77-year-old man comes to the office for a routine checkup. His wife reports that he frequently does not remember conversations they have had or details from television shows he has watched. She is not sure if this is due to poor hearing or poor memory. She thinks he may not be as sharp cognitively as he used to be, even when he is reading or doing tasks that do not involve hearing. The wife is concerned about the patient’s cognition and risk of future decline.
Which one of the following is true for patients with hearing impairment?
(A) Hearing loss is associated with mild cognitive impairment but not dementia. (B) Hearing loss does not affect long-term memory. (C) The degree of hearing impairment does not correlate with risk of dementia. (D) Tests with verbal and nonverbal stimuli show similar patterns of cognitive impairment.
(D) Tests with verbal and nonverbal stimuli show similar patterns of cognitive impairment.
An 86-year-old woman is brought to the office for a follow-up visit, accompanied by her daughter (her durable power of attorney) and her caregiver. History includes Alzheimer disease, stage 4 lung cancer, and recent right lower-extremity deep-vein thrombosis. The caregiver states that the patient spends most of the day asleep, often difficult to arouse. Her appetite has decreased notably in the last 6 weeks; at her visit to the oncologist 1 month ago, weight was down by 2.3 kg (5 lb). At that visit, the option of hospice was discussed with the patient’s daughter. The daughter is not ready for her mother to start hospice care and asks what can be done to improve her caloric intake. On examination, weight has decreased further by 4.6 kg (10 lb).
Which one of the following is the most appropriate initial recommendation for this patient?
(A) Oral dronabinol 2.5 mg twice daily (B) Oral megestrol acetate 400 mg/d (C) Placement of gastrostomy tube for enteral feedings (D) Small meals of the patient’s favorite foods
(D) Small meals of the patient’s favorite foods
NEVER (C)
Name the pharmacologic class and mechanism of action of donepezil
Acetylcholinesterase inhibitor; inhibits the breakdown of acetylcholine which is thought to help with memory function
This intracellular protein forms neurofibrillary tangles associated with both AD and frontotemporal dementia
Tau
Sudden onset, stepwise progression
Abnormal neurologic exam
Ischemic lesions on head CT or MRI
Vascular dementia
An 82-year-old man comes to the office for his annual wellness visit. His wife is concerned that his thinking has slowed considerably over the last 2–3 years and that he does not focus as well as previously. Calendars, notes, and other reminders help, but he can no longer manage household finances or organize his medications without assistance.
He has insight into his deficits. History includes hypertension, diabetes mellitus, coronary artery disease, and prior stroke.
On physical examination, there is mild left facial droop, mild left arm spasticity and pronator drift without overt weakness, and hemiparetic gait.
Laboratory findings:
Magnetic resonance imaging of the brain shows moderate bilateral white matter hyperintensities on T2/FLAIR (fluid-attenuated inversion recovery) sequences, with evidence of several chronic lacunar infarctions.
Which one of the following is most likely to improve cognitive outcome over time?
(A) Exercise program (B) Omega-3 fatty acid supplementation (C) Cholinesterase inhibitor
(D) Statin
(A) Exercise program
An 80-year-old woman comes to the office because for the past 6 months she has had difficulty staying asleep, and she frequently naps during the day. She is accompanied by her husband. History includes moderate Alzheimer disease. She usually falls asleep easily around 9 or 10 PM, and then wakes up after 2 hours. She may get up to go to the bathroom, and the pattern of sleeping on and off for a few hours at a time continues until her scheduled wake time at 6 AM. She has at least 3 awakenings during the night, each lasting from 30 to >60 minutes. She sleeps after breakfast for 2 hours and takes 1 or 2 naps in the afternoon. She sometimes appears more agitated in the evening. The nighttime awakenings affect her husband’s sleep and overall quality of life.
Which one of the following is the best treatment approach for this patient’s sleep disorder?
(A) Melatonin at scheduled bedtime (B) Trazodone at scheduled bedtime (C) Cognitive-behavioral therapy for insomnia (D) Bright light exposure during the day
(D) Bright light exposure during the day
A 79-year-old woman is brought to the emergency department with a history of anxiety of 2–3 weeks. Her family reports worsening confusion and disorientation as well as behavior problems, including agitation and suicidal ideation. Her symptoms were initially attributed to worsening of her dementia but then accelerated. History includes dementia and hypertension. Current medications are donepezil, memantine, lisinopril, and paroxetine, which was prescribed for anxiety 2 months ago.
On examination, the patient is combative and disoriented. Laboratory findings include low serum sodium level and low plasma osmolarity. Urine sodium level and osmolarity are increased.
Which one of the following medications is the most likely cause of her hyponatremia?
(A) Donepezil (B) Paroxetine (C) Memantine
(D) Lisinopril
(B) Paroxetine
This protein is included in Lewy Bodies and is associated with both Parkinson's disease and dementia with Lewy Bodies
Alpha synuclein
Executive dysfunction
Spared memory and visuospatial skills
Early onset
Loss of empathy
Inappropriate behavior
Frontotemporal dementia
A 72-year-old woman comes to the office because she is concerned about changes in cognition. The changes have not affected her ability to function. History includes type 2 diabetes mellitus and osteoarthritis. Medication is limited to acetaminophen as needed for pain. She does not smoke tobacco, drink alcohol, or use illicit drugs. She has no symptoms of anxiety or depression. Vision and hearing are sufficient.
On examination, vision and hearing are normal. Screening assessment is consistent with cognitive decline.
Laboratory findings:
Magnetic resonance imaging of the brain shows no evidence of mass lesion, stroke, or other possible cause of cognitive decline.
Which one of the following is most likely to slow progression to dementia in this patient?
(A) Cholinesterase inhibitor (B) N-methyl-D-aspartate (NMDA) receptor antagonist (C) Nonsteroidal anti-inflammatory drug (NSAID) (D) Oral hypoglycemic agent
(D) Oral hypoglycemic agent
A 63-year-old man comes to the office accompanied by his wife, who is concerned about changes she has seen in his behavior over the past year. He is a retired army major. He has become messy and unpredictable; for example, last week she found him cutting up all the curtains in the house. He gorges on food and is no longer quiet and polite; instead, he has become abusive and now uses coarse language. During the interview, the patient is oblivious to his wife’s statements. History includes hypertension.
On examination, the patient appears unkempt. Hypertension is under control, and all other findings are normal, except for the Mini–Mental State Examination on which he scores 23.
Which one of the following is the most likely diagnosis?
(A) Delirium
(B) Frontotemporal lobar degeneration (C) Adjustment disorder following retirement (D) Substance use disorder
(B) Frontotemporal lobar degeneration
Antipsychotics may drastically worsen motor symptoms in this subtype of dementia (...and why?)
Dementia with Lewy Bodies
This sleep disorder is highly predictive of neurodegenerative disease secondary to alpha-synucleinopathies
REM Sleep Behavior Disorder
Frequent falls
Fluctuating attention and concentration
REM sleep behavior disorder
Recurrent well-formed visual hallucinations
Parkinsonism
Dementia with Lewy Bodies
A 90-year-old woman comes to the office accompanied by her daughter, who serves as her primary caregiver. The patient started donepezil for Alzheimer disease 6 months ago. The dosage was titrated from 5 mg/d to 10 mg/d at 1 month but was decreased back to 5 mg/d 3 months ago because of increasing gastrointestinal adverse effects (diarrhea and fecal urgency, with occasional fecal incontinence). The patient’s daughter reports that, overall, her mother’s cognitive function has stabilized since starting the acetylcholinesterase inhibitor, and she would like to continue it. Over the past few weeks, however, the mother asks to void up to 10 times daily. After consultation with their local pharmacist, they were informed that urinary frequency is an adverse drug event associated with donepezil. The daughter asks about strategies to manage the urinary frequency; she is open to additional drug therapy. The mother’s history includes hypertension; her blood pressure has been maintained at goal with amlodipine 10 mg/d.
On physical examination, blood pressure is 124/76 mmHg. There is no evidence of pelvic organ prolapse or atrophic vaginitis. Ultrasonography of the bladder shows postvoid residual of 45 mL within 15 minutes of a void.
Which one of the following medications would be appropriate to consider for her urinary symptoms?
(A) Oxybutynin
(B) Tolterodine
(C) Mirabegron
(D) Diphenhydramine
(C) Mirabegron
A 73-year-old man comes to the office because he is concerned about his risk of Alzheimer disease. His father was diagnosed with Alzheimer disease at age 73; there is no other family history of Alzheimer disease or other dementias. The patient has no cognitive symptoms and is in good health. He had a mild traumatic brain injury last year after a fall, but symptoms and signs resolved. He drinks alcohol, 1 or 2 standard drinks 3 days each week, but there is no evidence of alcohol abuse.
Which one of the following increases this patient’s long-term risk of Alzheimer disease, compared with other older adults?
(A) His age
(B) Parent with Alzheimer disease (C) Head injury without loss of consciousness (D) Excess alcohol intake
(B) Parent with Alzheimer disease
What is the FDA black box warning on all antipsychotics for patients with dementia?
Increase in all-cause mortality
(YIKES!)
Specific alleles involved in the development of this protein, associated with beta-amyloid clearance, are known to alter an individual's risk of developing Alzheimer's Disease
Apolipoprotein E
How do you distinguish between DLB and Parkinson's disease dementia?
Timing and onset of cognitive changes:
DLB = Tremor/motor symptoms start within 1 year of cognitive changes
PDD = Motor symptoms precede cognitive changes by at least 1-2 years and typically longer
A 75-year-old man is brought to the office by his wife because he has had progressive cognitive and behavioral decline for the last 3 years. The wife reports a decline in memory, attention, and organizational ability sufficient to impair his daily function. The patient reports a decline in his sense of smell. He has had progressive weight loss. He has been acting out his dreams for many years; more recently, he has behavioral disturbance that is worse at night, with frequent delusions and intermittent hallucinations.
Which one of the following clinical features is most useful for differentiating dementia with Lewy bodies from Alzheimer disease?
(A) Psychosis (B) Hyposmia (C) Memory impairment
(D) Rapid eye movement (REM) sleep behavior disorder
(D) REM sleep behavior disorder
An 80-year-old woman comes to the office because she has worsening symptoms of anxiety. Generalized anxiety disorder was diagnosed 3 years ago and remitted with administration of sertraline, which she continues to take. Six months ago, she came to the office accompanied by her daughter, who said that the patient had been having problems with memory for several months. Mild cognitive impairment was diagnosed.
Which one of the following is the most likely explanation for her current symptoms?
(A) Progression of cognitive impairment (B) Advanced age
(C) Recurrence of generalized anxiety disorder (D) Cognitive impairment secondary to anxiety disorder
(A) Progression of cognitive impairment
Name the pharmacologic class and mechanism of action of memantine
NMDA antagonist; has neuroprotective effects by reducing glutamate-mediated excitotoxicity