Presentation: Strange change
Mr. A, age 66, has lived an active life but now just sits around most of the day. Once an early riser, he is sleeping until 11 AM or noon daily. His wife frequently must motivate him to get out of bed.
Mr. A’s wife describes him as good-natured and extroverted, but she says lately he has also become increasingly withdrawn and quiet. People often think he is angry with them.
His dining habits also have changed. He used to wait until everyone had been served before beginning his meal, but he now starts eating immediately. He often overeats and has gained 15 pounds over 1 year.
Mr. A has always driven manual-transmission vehicles but has trouble remembering how to shift gears on his new car. While visiting his daughter, he could not operate the bathroom faucets properly and scalded himself. His daughter also noticed he does not wash his hands before eating or after toileting.
Findings. Mr. A presents to our clinic at his wife’s and daughter’s insistence but says his memory is fine and he can perform all activities of daily living (ADL). He denies depressive, anxiety, or psychotic symptoms but has hypertension and probable benign prostatic hypertrophy. He is taking ramipril, 5 mg/d for hypertension, donepezil, 10 mg/d for cognitive deficits, and aspirin, 325 mg/d to prevent a heart attack. Physical exam shows no gross neurologic abnormalities. Organ systems are normal.
Mr. A’s Folstein Mini-Mental State Exam (MMSE) score (22/30) indicates cognitive impairment. During his mental status exam, he is pleasant, cooperative, and makes good eye contact. He answers appropriately, but his speech lacks spontaneity. He smiles throughout the interview, even while discussing serious questions regarding his health. He is fully oriented but lacks insight into his deficits.
Brain MRI, ordered after he had presented to another hospital with similar complaints, is normal. PET scan shows frontal lobe hypometabolism, right greater than left, and mild underperfusion of the right basal ganglia and right temporal lobe.
Frontotemporal dementia subtypes and their clinical features
|Corticobasal degeneration||Onset around age 60|
|Symptoms may be unilateral at first and progress slowly|
|Poor coordination, akinesia, rigidity, disequilibrium, limb dystonia|
|Cognitive and visual-spatial impairments, apraxia, hesitant/halting speech, myoclonus, dysphagia|
|Eventual inability to walk|
|Frontotemporal dementia with motor neuron disease||Behavioral changes, emotional lability|
|Decreased spontaneous speech|
|Bulbar weakness with dysarthria and dysphagia, weakness, muscle wasting, fasciculations in hands and feet|
|Frontotemporal dementia with parkinsonism linked to chromosome 17||Behavioral disturbance, cognitive impairment, parkinsonism|
|Neurologic symptoms usually arise in patients’ 30s to 50s|
|Progressive fluent aphasia (semantic dementia)||Trouble remembering words|
|Loss of semantic memory, although episodic memory is good|
|Symmetric anterolateral temporal atrophy; hippocampal formation relatively intact|
|Atrophy usually more pronounced on the left side4|
|Progressive nonfluent aphasia||Behavioral changes rare|
|Global cognition declines over time|
|Speech dysfluency, difficulty finding words, phonologic errors in conversation; comprehension is preserved|
The authors’ observations
Mr. A’s clinical course suggests frontotemporal dementia (FTD), a spectrum of non-Alzheimer’s dementias characterized by focal atrophy of the brain’s frontal and anterior temporal regions (Table 1). These dementias loosely share clinicopathologic features, including:
- decline in social interpersonal conduct
- emotional blunting
- loss of insight
FTD is the second most-common cause of dementia after AD in the years preceding old age but remains underdiagnosed. Onset is most common between ages 45 to 65 but can occur before age 30 and in the elderly.
FTD’s clinical presentation usually reflects distribution of pathologic changes rather than a precise histologic subtype. Major clinical presentations include a frontal or behavioral variant (frontal variant FTD associated with corticobasal degeneration or motor neuron disease), a progressive fluent aphasia (temporal lobe variant FTD), and a progressive nonfluent aphasia. Mr. A’s lack of initiative, emotional reactivity, and loss of social graces with normal speech pattern suggest frontal variant FTD.
Behavioral changes associated with FTD include:
- Decline in social conduct, including tactlessness and breaches of etiquette, associated with predominantly right-hemisphere pathology.3
- Apathy, which correlates with severity of medial frontal-anterior cingulate involvement.
- Dietary changes—typically overeating (hyperorality) with a preference for sweets.4
Cognitive changes in FTD—attentional deficits, poor abstraction, difficulty shifting mental set, and perseverative tendencies—point to frontal lobe involvement.3
Neurologic signs usually are absent early in the disease, although patients may display primitive reflexes. As FTD progresses, patients may develop parkinsonian signs of akinesia and rigidity, which can be marked. Some develop neurologic signs consistent with motor neuron disease.3