Frontotemporal Dementia

FTD typically affects individuals in their 50s to 60s.

• It is the second-most common cause of early-onset dementia but involves behavioral or cognitive (including language) domains out-of-proportion to the memory loss.
• It is autosomal dominant in ~ 40% of cases with the remaining being sporadic.

What defines these dementias is the finding of frontotemporal lobar degeneration but because all FTDs have varying degrees of frontotemporal atrophy what’s used to reliably distinguish them, pathologically, is their molecular signature. At present, three key known molecular classes are:

• Tau.
• Pick bodies along with tau. They are round-shaped, intraneuronal inclusions of tau protein that are argyrophilic (they have affinity for silver staining).
• TDP-43 (TAR DNA-binding protein of 43kDA)
• FUS (Fused in Sarcoma)

Apathy

• Apathy correlates to the anterior/medial surface of a brain (we show profound frontal lobe atrophy).

Impulsivity (aka disinhibition)

• Impulsivity localizes to the orbitofrontal cortex. We show atrophy of the frontal and temporal lobes in lateral view (with preserved cortical bulk in the parietal and occipital lobes).

Behavioral variant FTD is a progressive neurodegenerative disorder that involves behavior and/or cognitive dysfunction with prominent involvement of any of the following symptoms:

• Impulsivity (disinhibition) (think: orbitofrontal degeneration)
• Apathy (think: anterior cingulate gyrus)
• Loss of empathy (think: amygdala and temporal atrophy)
• Perserverative/stereotyped behavior (think: frontal and temporal lobes (eg, complex partial seizures))
• Hyperorality (think: amygdala and Kluver Bucy syndrome)
• Executive dysfunction (think: prefrontal cortices)

Consistent with the localization of Broca’s aphasia, progressive nonfluent aphasia localizes to the inferior frontal lobe.

• Deficit begins as a transcortical motor aphasia with progression to Broca’s aphasia.
• It is agrammatic, hesitant, nonfluent with preservation of word meaning but dysfunction in understanding complex grammatical arrangements.

Semantic variant PPA localizes to the anterior temporal lobe (with profound anterior temporal pole atrophy being a key finding).

• The deficit begins as a transcortical sensory aphasia with progression to Wernicke’s aphasia.
• There is a loss of word meaning, meaning the fluency and melody of speech is preserved but the content is empty.
• There is a lack of understanding of basic definitions and a substitution of content with jargon phrases.
• There is an ultimate progression towards word salad: nonsensical sentences devoid of meaning.

FTD is often categorized along with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), which we address in the hypokinetic movement disorders tutorial.

• See the Non-Alzheimer's Disease tutorial