Frontotemporal Neurocognitive Disorder Diagnosis and Characteristics

Core Clinical Features

The American Academy of Neurology suggests that frontotemporal neurocognitive disorder (FTD) is a progressive neurodegenerative disease characterized by selective degeneration of the frontal and temporal lobes, presenting primarily with behavioral changes, personality alterations, and/or language deficits, typically beginning between ages 40-70 years 1, 2
FTD represents one of the most common forms of early-onset dementia in patients under 65 years of age, according to the American Academy of Neurology 1

The National Institute of Neurological Disorders and Stroke indicates that social cognition deficits are the hallmark of FTD, including impaired emotion recognition, theory of mind deficits, reduced empathy, and impaired moral reasoning 3, 4
Action naming is more affected than object naming in FTD patients, as stated by the American Academy of Neurology (the reverse pattern of Alzheimer's disease) 4, 5
Approximately 10% of pathologically-confirmed cases show marked episodic memory deficits at presentation, contrary to diagnostic criteria, according to the National Institute of Neurological Disorders and Stroke 4, 5

The American Psychiatric Association notes that approximately 50% of FTD patients receive an initial psychiatric misdiagnosis, with diagnostic delays averaging 5-6 years 1
Insidious onset with gradual, progressive deterioration is a key differentiating feature of FTD from psychiatric disorders, as stated by the American Academy of Neurology 1, 2

The National Institute of Neurological Disorders and Stroke suggests that genetic testing for C9orf72 should be performed in all possible/probable FTD cases or suspected cases with strong psychiatric features 6
Approximately 20-40% of cases have a family history, with autosomal dominant inheritance in one-third to one-half of familial cases, according to the American Academy of Neurology 1

The American Academy of Neurology indicates that structural MRI shows frontal and anterior temporal lobe atrophy in FTD patients, though sensitivity is only 70% in early stages 1, 2

The American Academy of Neurology notes that dismissing FTD diagnosis due to positive psychiatric history is a major pitfall, as psychiatric symptoms can be the initial presentation of FTD 2
Relying on patient self-report is also a pitfall, as impaired insight is characteristic of FTD, according to the American Academy of Neurology 2
Missing diagnosis due to family psychiatric history is another pitfall, as genetic FTD can present with psychiatric phenotypes, as stated by the National Institute of Neurological Disorders and Stroke 1

Emotional blunting with absence of subjective distress is a key differentiator from psychiatric disorders, with patients lacking emotional distress and showing marked lack of insight, according to the Brain journal 7

No disease-modifying treatments exist, and management focuses on behavioral interventions and symptomatic support, as stated by the Ca-A Cancer Journal for Clinicians 8
Avoid cholinesterase inhibitors and memantine, as they have no consistent benefit in FTD, unlike Alzheimer's disease, according to the Ca-A Cancer Journal for Clinicians 8
Antipsychotics should be used with extreme caution only for severe agitation, due to increased risk of falls, stroke, and death, as noted by the Ca-A Cancer Journal for Clinicians 8

In patients with suspected behavioral‑variant frontotemporal dementia, the neurological examination should actively search for motor‑neuron disease signs (e.g., weakness, fasciculations) and primitive reflexes such as the grasp reflex. 9
Early detection of progressive supranuclear palsy can be aided by noting the absence of normal optokinetic nystagmus and a slowing of downward saccades. 9
The corticobasal syndrome is characterized by asymmetric rigidity, the alien‑hand phenomenon, apraxia, and cortical sensory deficits. 9
Distinctive features of corticobasal syndrome also include unilateral dystonia, stimulus‑sensitive myoclonus, and ideomotor apraxia. 9

Mutations in C9orf72, MAPT, and GRN represent the most common genetic causes of frontotemporal dementia, accounting for 20–40 % of cases with a positive family history. 10
Genetic testing for the C9orf72 repeat expansion should be performed in all possible or probable cases of behavioral‑variant frontotemporal dementia, particularly when prominent psychiatric manifestations are present. 10
Carriers of the C9orf72 expansion may exhibit heterogeneous neuropsychiatric phenotypes (e.g., late‑onset psychosis or mania) without a known family history, sometimes emerging several years before typical behavioral‑variant frontotemporal dementia features. 11

A positive family history of psychiatric illness can bias clinicians toward missed diagnoses of behavioral‑variant frontotemporal dementia. 11