Neurocognitive Disorders

Evaluate the following clinical scenarios detailing distinct neurocognitive or acute neuropsychiatric presentations. Pair each patient vignette with the single most appropriate next step in management or definitive therapeutic intervention.

A 48-year-old man is brought to the clinic by his sister due to a 5-month history of progressive forgetfulness, social withdrawal, and difficulty concentrating. The sister reports that he takes an unusually long time to answer simple questions and that his walking has become slow and uncoordinated. His medical history is significant for HIV infection, diagnosed 12 years ago. He admits to poor adherence to his antiretroviral therapy over the past 18 months. His most recent CD4+ T-cell count was 145/mm³. Vital signs are within normal limits. Neurological examination reveals marked psychomotor slowing, saccadic pursuit eye movements, and brisk deep tendon reflexes in the bilateral lower extremities. His Montreal Cognitive Assessment score is 19/30. Magnetic resonance imaging of the brain demonstrates diffuse cortical atrophy and symmetric, bilateral periventricular white matter hyperintensities without contrast enhancement or mass effect. Which of the following is the most likely diagnosis?

A 74-year-old retired teacher is brought to her primary care physician by her daughter due to progressive forgetfulness and difficulty managing her finances over the past two years. Her medical history includes well-controlled hypertension and hyperlipidemia. The physician suspects a major neurocognitive disorder. Arrange the following diagnostic steps in the most appropriate sequential clinical workflow, from the initial encounter to advanced diagnostic testing.

A 75-year-old man is brought to the clinic by his daughter for a cognitive evaluation. Over the past 5 months, he has stopped managing his finances, spends most of the day sitting in a recliner, and frequently complains that his memory is 'completely gone.' When the physician asks him to perform serial sevens and recall three objects, he sighs loudly, states 'I just cannot do this anymore,' and refuses to try. Five months ago, he was forced to surrender his driver's license due to worsening macular degeneration. His daughter notes that he has lost 4.5 kg (10 lb) during this period. Neurologic examination is nonfocal. Which of the following is the most likely diagnosis?

Match each clinical presentation of cognitive decline to its most likely underlying pathophysiologic mechanism.

Evaluate the clinical scenarios describing older adult patients presenting with progressive cognitive or behavioral changes. Match each distinct clinical presentation with its definitive diagnostic finding or most likely underlying pathophysiological mechanism.

A 58-year-old man is brought to the clinic by his husband due to a 14-month history of progressive behavioral changes. Previously known as a meticulous and empathetic high school teacher, the patient has become increasingly apathetic and frequently makes sexually explicit remarks to neighbors. He recently ate a stranger's sandwich off their plate at a local restaurant and showed no remorse when confronted by the staff. He denies feeling sad or anxious, stating, "Everything is perfectly fine." The patient has a remote history of a single depressive episode in his 20s. He takes over-the-counter diphenhydramine occasionally for sleep but takes no prescription medications. Vital signs are within normal limits. Laboratory studies, including a thyroid-stimulating hormone (TSH) level of 1.2 mU/L and a free T4 of 1.2 ng/dL (normal: 0.8-1.8 ng/dL), are normal. On mental status examination, he has a blunted affect and poor insight, but no delusions or hallucinations are elicited. Montreal Cognitive Assessment (MoCA) score is 23/30; he loses points primarily on clock drawing and verbal fluency tasks, but successfully recalls 3 out of 3 objects after a 5-minute delay. Neurological examination reveals no focal weakness, rigidity, or resting tremor. Which of the following is the most likely diagnosis?

A 72-year-old woman is evaluated in the outpatient geriatric clinic due to progressive memory impairment and behavioral changes. According to her son, who accompanies her, she has experienced significant day-to-day fluctuations in her alertness and attention over the last 10 months. Furthermore, she frequently describes seeing detailed, silent figures of people standing in her bedroom. Her sleep is often restless, and she frequently shouts and thrashes her arms as if she is acting out her dreams. On physical examination, the patient has a mask-like facial expression, a resting tremor in her left hand, and cogwheel rigidity in both upper extremities. The physician explains the likely diagnosis to the son and discusses management options. The physician strongly cautions against the use of a specific class of medications to treat her perceptual disturbances, noting that it could trigger a severe, potentially fatal reaction characterized by irreversible parkinsonism and autonomic dysfunction. Which of the following medications is most likely to cause the severe reaction described by the physician?

During morning rounds on a surgical ward, an internal medicine consultant is asked to evaluate a patient recovering from a right femoral neck fracture repair performed 48 hours ago. The nursing staff reports that the patient was awake, alert, and conversational yesterday, but overnight she became highly agitated, attempted to remove her urinary catheter, and claimed that insects were crawling on her bed sheets. The patient's daughter confirms her mother lived independently and had no history of memory issues or psychiatric illness prior to the fall. Physical examination reveals an inattentive patient who drifts off to sleep during questioning. Vital signs are stable, and a basic metabolic panel is unremarkable. Which of the following is the most likely diagnosis for this patient's acute presentation?

A 73-year-old retired architect is evaluated in the hospital for severe agitation. He was admitted 24 hours ago for cellulitis of the right lower extremity, for which wound cultures grew methicillin-resistant *Staphylococcus aureus* (MRSA). His medical history is significant for bipolar I disorder (not currently taking mood stabilizers), severe osteoarthritis (managed with scheduled tramadol), and a 3-year history of progressive cognitive decline, prominent visual hallucinations of small animals, and a resting tremor. He has a documented diagnosis of major neurocognitive disorder with Lewy bodies.

Currently, he is severely agitated, attempting to pull out his intravenous line, and striking at the nursing staff. He is unable to cooperate with a medical examination or verbal de-escalation. His husband, who is his legally appointed healthcare proxy, requests that the medical team administer medication to calm him down. However, the patient's daughter, who just arrived, demands that no mind-altering medications be given and suggests using physical restraints instead.

Which of the following is the most appropriate next step in the management of this patient?

A 72-year-old woman is brought to the clinic by her son due to a 6-month history of progressive memory impairment, apathy, and severe psychomotor slowing. She frequently forgets conversations and has stopped participating in her usual social activities. She also reports worsening fatigue, constipation, and feeling cold constantly. Her medical history is significant for bipolar I disorder, which has been well-controlled on lithium monotherapy for 15 years, and hypertension. Current medications are lithium and lisinopril. Vital signs show a blood pressure of 130/80 mm Hg and a heart rate of 52/min. Physical examination reveals delayed relaxation of the deep tendon reflexes, dry skin, and a slightly puffy face. Cognitive assessment yields a Montreal Cognitive Assessment (MoCA) score of 19/30.

Laboratory results are as follows:

Which of the following is the most appropriate next step in management?

A 64-year-old man is brought to the neurologist by his wife due to a 3-month history of rapidly progressive cognitive decline and unusual involuntary movements. The wife notes that he initially had trouble concentrating at work and seemed unusually anxious. Over the past month, he has become profoundly disoriented, struggles to walk independently due to poor coordination, and frequently exhibits sudden, brief, shock-like muscle jerks, particularly when startled by a loud noise. He has no significant past medical history and takes no medications. Vital signs are normal. Neurological examination reveals marked gait ataxia, widespread myoclonus, and severe expressive aphasia. Magnetic resonance imaging (MRI) of the brain demonstrates hyperintensity in the basal ganglia and cerebral cortex on diffusion-weighted imaging. Which of the following best describes the underlying pathophysiology of this patient's condition?

A 74-year-old woman is brought to the emergency department from her home by her daughter due to severe confusion and agitation that began yesterday. The daughter reports that the patient was previously able to manage her daily activities but has been 'talking to people who aren't there' and pacing the house incessantly over the past 24 hours. The patient has a history of major depressive disorder and mild cognitive impairment. Two days ago, she developed a runny nose and began taking an over-the-counter cold and allergy medication. Her prescribed medications include daily citalopram. Routine laboratory results from a clinic visit one week ago showed a decreased free thyroxine (T4) level with a normal thyroid-stimulating hormone (TSH) level. On physical examination, her temperature is 37.8°C (100.0°F), pulse is 112/min, and blood pressure is 142/86 mm Hg. She is disoriented to place and time. Her skin is warm, flushed, and dry. Her pupils are 7 mm bilaterally and sluggishly reactive to light. Bladder ultrasound reveals 600 mL of retained urine. Which of the following is the most likely cause of this patient's acute presentation?

A 75-year-old man is brought to the neurology clinic by his son. Over the past 8 months, the patient has developed a progressively unsteady gait. The son describes his father's walking as feeling "glued to the ground" with very short steps. For the past 4 months, the patient has had difficulty managing his finances, exhibits new-onset apathy, and struggles with short-term memory. Over the last month, he has had multiple episodes of urinary incontinence, toward which he appears indifferent. His medical history includes hypertension and type 2 diabetes mellitus. Neurological examination reveals a broad-based, magnetic gait, but muscle strength and deep tendon reflexes are normal. A magnetic resonance imaging (MRI) scan of the brain is obtained and is shown below, demonstrating enlarged lateral and third ventricles with relatively normal, uncrowded cortical sulci. What is the most appropriate next step in the management of this patient?

A 58-year-old man is brought to the clinic by his wife due to an $8$-month history of progressive behavioral changes. His wife reports that he has become increasingly apathetic and socially withdrawn, frequently neglecting his personal hygiene. He recently began compulsively hoarding empty glass bottles and has made sexually explicit remarks to neighbors, which is entirely out of character. The patient has a history of bipolar I disorder following a single manic episode at age 22, but he has been euthymic and off psychiatric medications for over $30$ years. Mental status examination reveals an alert and oriented patient with a blunted affect. He displays poor insight and disinhibition during the interview. Memory recall is 3/3 after $5$ minutes, but he exhibits significant impairment on the Trail Making Test Part B. Laboratory studies show a thyroid-stimulating hormone (TSH) level of $0.2 \mu U/mL$ (Normal: $0.4-4.0 \mu U/mL$) and a free thyroxine (T4) level of $0.6 ng/dL$ (Normal: $0.9-1.7 ng/dL$). The patient has a legally executed advance directive designating his eldest daughter as his sole healthcare proxy. However, the daughter is not present, and the wife vehemently demands the physician immediately start an antidepressant, believing his symptoms represent a severe depressive relapse. Which of the following is the most appropriate next step in management?

A $72$-year-old woman is brought to the geriatrics clinic by her husband due to progressive memory loss and confusion over the past $3$ months. Her husband states she spends most of her day in bed, has stopped cooking, and has lost $5$ kg ($11$ lb). Over the last $3$ weeks, she has been repeatedly stating that "the government is coming to arrest me for tax fraud," which is completely unfounded.

Past medical history is significant for Parkinson disease, treated with selegiline, and bipolar I disorder. She previously took lithium but discontinued it a year ago of her own volition.

On mental status examination, she exhibits marked psychomotor retardation and poor eye contact. When asked to perform serial sevens or spell "WORLD" backwards, she gives minimal effort, frequently stating, "I don't know, my mind is completely gone."

Her daughter, who is her legally appointed healthcare proxy, lives in another state. Her husband is frustrated with the patient's decline and demands that the physician immediately authorize her placement in a local nursing home.

Which of the following is the most appropriate next step in the management of this patient?

A 78-year-old man residing in an assisted living facility is evaluated for a decline in his cognitive abilities over the past 3 months. The nursing staff report that he has stopped participating in social activities, frequently stays in his room with the blinds drawn, and has lost 4.5 kg (10 lb) during this period. When asked about his memory, the patient becomes distressed and repeatedly states, "My mind is completely gone; I cannot remember anything anymore." On cognitive testing, he makes poor eye contact and frequently responds to questions with "I don't know," exhibiting minimal effort. However, when strongly encouraged by the examiner, he successfully performs complex attention tasks. His neurological examination shows no focal deficits. A non-contrast head CT performed 2 months ago after a mechanical fall was unremarkable. Laboratory studies, including thyroid-stimulating hormone and vitamin B12, are within normal limits. Which of the following is the most appropriate initial management for this patient?

A 78-year-old woman with a 6-year history of Alzheimer disease is brought to the clinic for a routine follow-up. Her family asks the physician about the natural progression of the disease to help them prepare for future care needs. The physician explains the typical chronological decline expected in this condition. Arrange the following clinical features in the correct chronological sequence that they typically appear during the natural course of Alzheimer disease, from earliest to latest.

A 72-year-old woman is brought to the outpatient geriatric psychiatry clinic by her son due to a 6-month history of significant cognitive decline. He reports that she has become increasingly withdrawn, spends most of the day in bed, and has stopped managing her household finances. During the interview, she makes poor eye contact, exhibits psychomotor retardation, and frequently answers "I don't know" rather than attempting to answer orientation or memory questions. Her Montreal Cognitive Assessment (MoCA) score is 19/30. Medical history is significant for bipolar I disorder that was well-controlled on lithium for two decades; however, she discontinued all medications 14 months ago following the death of her husband. Her son notes she has not had any periods of elevated mood, decreased need for sleep, or rapid speech since stopping her medication. Vital signs and physical examination are normal. Laboratory studies, including complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and vitamin B12 levels, are within normal limits. The physician determines that her cognitive deficits are secondary to a severe mood episode rather than a primary neurodegenerative process. Which of the following is the most appropriate initial pharmacological intervention for this patient?

A 70-year-old man is brought to the clinic by his son due to memory issues that began 2 months ago, shortly after the sudden death of his wife. The patient frequently complains about his memory, stating, "My brain is just broken; I can't remember anything." During cognitive testing, he puts forth poor effort and frequently answers "I don't know" to questions, though he can often provide the correct answers when gently prompted. He also reports early morning awakenings, decreased appetite, and a 4-kg (8.8-lb) weight loss over this period. His physical and neurological examinations are unremarkable. Which of the following is the most likely diagnosis?