In some writings on this subject, the term frontotemporal dementia has come to be used in a highly restricted sense, being assigned to cases that show only tau-staining material in neurons. Many of the cases are sporadic, but the inherited varieties of the behavioral variant of the disorder noted below may explain up to 40 percent and are linked to any of several genes, mainly related to tau (e.g., microtubule associated protein [MAPT], progranulin [GRN] both on chromosome 17) supports its distinction as a separate entity; it is in these cases that the intraneural deposition of tau is most striking, in both the frontotemporal cortex and the substantia nigra. These mutations alter the proportions of different isoforms of this protein and lead both to tau accumulation and its hyperphosphorylation. Indeed, many cases of frontotemporal dementia are associated with tau gene mutations. However, abnormal aggregates of tau have been identified in practically all neurodegenerative atrophies and, of course, form the main constituent of the paired helical filaments (neurofibrillary tangles) of Alzheimer disease, and in progressive supranuclear palsy where they are abundant, although of slightly different structure. From the observations of workers such as Neary and of Neary and colleagues, pure tau-reactive cases outnumber Pick disease when the latter is strictly defined by the cortical white matter degeneration and Pick inclusions. Finally, the aphasic variants of FTD are as, or more often, associated with Alzheimer changes, making the category difficult to navigate.
Behavioral variant FTD Patients under consideration with behavioral changes present with personality and related abnormalities that include apathy, disinhibition, perseveration, poor judgment and limited ability for abstraction, loss of empathy, bizarre affect, eating disorders, and a general disengagement. Insight is almost always impaired and some subjects become euphoric or display repetitive compulsive behaviors. An initial diagnosis of depression has been common. Other psychiatric symptoms such as sociopathic and disinhibited behavior with aspects of hyperorality and hyperphagia may predominate late in the illness. Utilization behavior (the compulsive use of implements and tools put before the patient) is also displayed in advanced cases.
CT, MRI, and functional imaging demonstrate a disproportionate atrophy and hypofunction in the frontal lobes, usually asymmetric. A proportion of patients with this type of frontotemporal dementia have parkinsonian features. A form of motor neuron disease is also linked to frontotemporal dementia in a small number of cases. This is particularly the case in the Guamanian (now called western Pacific) variety and in the heredofamilial frontotemporal atrophy linked to a mutation in TAU on chromosome 17.
Nonetheless, a frontotemporal dementia identical to that of the tau-reactive cases has been observed in others without any tau or synuclein staining of neurons.
Primary progressive aphasias (PPA) Focal disturbances, particularly aphasia and apraxia, occur early and prominently in certain patients with lobar degenerations, indicating a lesion in the left frontal or temporal lobes. Viewed from another perspective, a prominent language disorder has been described in almost two-thirds of all patients with temporal lobe atrophy.
Several types of this disturbance have been delineated. In the first, progressive nonfluent aphasia, the patient initially speaks less and has word-finding difficulty (anomia), but language structure is intact (Mesulam, 1982); later, he may forget and misuse words and soon fails to understand much of what is heard or read. Sentences are short and telegraphed. Later, dysarthria and apraxia become apparent and finally, the patient is virtually mute, seemingly without impulse to speak, and with an inability to form words (Snowden et al, 1992).