Frontotemporal dementia. Clinical and pathophysiological aspects

Symptomatological, brain imaging and neurochemical aspects of clinical frontotemporal dementia (FTD) were studied. The diagnoses of FTD were established according to international consensus criteria. FTD was compared with other common types of dementia for which the pathophysiology is better known. FTD differed from vascular dementia with a dominating frontal lobe syndrome (VAD-F) with regard to the symptomatology. At onset, memory disturbances, confusion and unspecific neurological signs were significantly more common in VAD-F than in FTD, and at the time of the clinical investigation, the FTD patients still had a more pronounced frontal syndrome. With regard to an anterior to posterior regional cerebral blood flow (rCBF) ratio, FTD differed from early onset Alzheimer's disease (EAD), late onset Alzheimer's disease (LAD), subcortical white matter dementia (SWD) and normal controls with high sensitivity and moderate to high specificity, which suggests that this ratio is useful in differential diagnosis. The FTD patients also had a more pronounced frontal atrophy on CT/MRI of the brain than the SWD patients. The cerebrospinal fluid (CSF) levels of the monoamine metabolites were found to be disturbed in FTD. Especially HVA, the dopaminergic metabolite, was decreased in FTD, but HMPG, the noradrenergic metabolite, was normal, which distinguished FTD significantly from EAD and LAD. Normal CSF levels of tau (a cytoskeleton-associated protein), b-amyloid1-42 (the core protein in senile plaques) and GAP-43 (a presynaptic protein) were found in FTD. FTD thereby differed from EAD and LAD in which increased CSF-tau and decreased CSF-b-amyloid1-42 levels were found. The CSF levels of the light subtype of the neurofilament protein (NFL) was highly increased in FTD, but normal in EAD. The results suggest that a pronounced frontal lobe syndrome, with a hypofrontal regional rCBF pattern and frontal cortical atrophy on structural brain imaging is characteristic of FTD. Normal CSF levels of tau, b-amyloid1-42, and GAP-43 suggest absence of neurofibrillary tangles, senile plaques and widespread presynaptic degeneration in FTD. The increased CSF-NFL levels in FTD suggest that some cytoskeleton proteins play a part in the pathophysiology of FTD, while others, such as tau, might not be involved to the same extent. Since there are no or only slight white matter changes in FTD, the increase in CSF-NFL must be unrelated to these changes