History and exam

Key diagnostic factors

common

coarsening of personality, social behavior, and habits

Predominance at presentation of coarsening of personality as manifested by characteristics such as disregard for social conventions, slovenly appearance, impatience and irritability, argumentativeness, lewd and tactless remarks, childlike and impulsive actions, loss of empathy and concern for others, compulsions, and rigid adherence to routines.

Changes in personality, habits, and activity generally precede the development of memory impairment, disorientation, or apraxias.

Poor emotional processing is detectable in patients with all 3 FTD subtypes, and is an important clinical feature in behavioral variant FTD and semantic dementia.[66]

progressive loss of language fluency or comprehension

Characteristic of the primary progressive subtype of FTD. Changes in language generally precede the development of memory impairment, disorientation, or apraxias.

development of memory impairment, disorientation, or apraxias

Generally preceded by changes in personality, language, habits, and activity.

progressive self-neglect and abandonment of work, activities, and social contacts

Generally presents with a history of progressive self-neglect and abandonment of work, activities, and social contacts.

Other diagnostic factors

common

early age at onset

Onset of progressive cognitive and behavioral decline in midlife or earlier. The average age of onset is between 45 and 65 years, but there have been documented cases in patients below 30 years and in older people.[83] Prevalence peaks in the seventh decade.[1][4] In one systematic review, FTD accounted for an average of 2.7% of all dementia cases among prevalence studies that included people 65 years and older, compared with 10.2% in studies restricted to those under 65 years.[21]

family history of FTD

Between 10% and 30% of cases probably have an autosomal dominant transmission. A family history of FTD is present for 25-50% of patients with autosomal dominant inheritance with mutations in several genes. The behavioral forms of FTD are the most heritable. Known mutations in the MAPT, PGRN, and C9orf72 genes each account for between 5% and 10% of all FTDs.[30]

altered eating habits

Altered eating habits may include fads and binge eating disorder.

Patients frequently exhibit altered food preferences, commonly craving sweet foods or carbohydrates, or expressing rigid preferences for particular foods.[84]

inattentiveness, puerile preoccupations, economy of effort, impulsive responding, and compulsive behaviors

These are often observed during cognitive tests and may account for low test scores. The most commonly observed repetitive behaviors among patients with behavioral variant FTD in one study were stereotypies of speech (35.5%), simple repetitive movements (15.2-18.6%), hoarding and collecting (16.9%), and excessive or unnecessary trips to the bathroom (13.5%).[85]

uncommon

signs of amyotrophic lateral sclerosis (ALS)

FTD may be associated with ALS, the signs of which include progressive asymmetric weakness of spinal or bulbar muscles and muscle wasting.

parkinsonian symptoms

Symptoms include tremor at rest, hypophonia, slowness of movement, narrowed range of facial expression, stooped posture, unsteadiness of gait (which is also associated with FTD, and suggestive of FTD with parkinsonism), corticobasal degeneration, and progressive supranuclear palsy.

fasciculations, atrophy, hyperreflexia, and other signs of motor neuron disease

Patients less commonly manifest signs of motor neuron disease.

glabellar, snout, sucking, rooting, or grasp reflex

Most patients have a normal neurologic exam in the early stages, or may have subtle signs suggestive of frontal lobe dysfunction.

loss of bladder and bowel control

Usually occur at advanced stage of the disease, although some men present with urinary urgency and incontinence.

Risk factors

strong

mutations in MAPT gene

Numerous mutations in the MAPT gene have been described.[30] These autosomal dominant mutations typically result in an FTD with parkinsonism phenotype (FTD with parkinsonism, corticobasal degeneration, and progressive supranuclear palsy). Specific mutations give rise to various different phenotypes and pathologic types.[52]

mutations in GRN gene

Numerous mutations in the GRN gene have been described.[30] These autosomal dominant mutations typically result in a behavioral FTD phenotype that may be associated with marked impairments of semantic knowledge (FTD, semantic dementia).

mutations in C9orf72 gene

Numerous mutations in the C9orf72 gene have been described.[30] These autosomal dominant mutations are typically associated with behavioral variant FTD, and there is also an association with FTD with motor neuron features.

weak

traumatic brain injury

FTD is more common in people who have had a traumatic brain injury (TBI) than in those who have not. It is also not known whether head trauma influences age at onset of dementia in patients who have a MAPT or PGRN mutation.[40][41][42] TBI with loss of consciousness occurring more than 1 year before diagnosis was associated with an earlier age of symptom onset and diagnosis in patients with behavioral variant FTD.[53] It is not known whether TBI influences age at onset of FTD associated with a gene mutation.

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