Frontotemporal dementia - symptoms and brain pathology

Sammanfattning: Frontotemporal dementia (FTD) is the clinical term for a heterogeneous group of dementia disorders with symptoms emerging from frontotemporal lobar degeneration (FTLD). FTD encompasses the behavioural variant (bvFTD) and the progressive aphasias: progressive non-fluent aphasia (PNFA) and semantic dementia (SD). Neuropathological classification is based on protein pathology with three major subgroups: Tau, TDP-43 and FUS. Early clinical diagnosis is challenging and prediction of neuropathological subtype is often not possible. The objective was to identify clinical markers (biomarkers or specific symptoms), of possible diagnostic value. In paper I potential cerebrospinal fluid biomarkers were examined. Increased neurofilament light protein (NFL) was seen in FTD compared to Alzheimer’s disease and healthy controls, particularly in the clinical subtype SD and in tau-negative cases. In paper II clinical and neuropathological characteristics in a large bvFTD family with a newly identified mutation (C9ORF72 expansion) were analysed. Despite age variations at onset and duration, symptomatology was strikingly homogenous. Unexpectedly, psychotic symptoms and extensive somatic complaints, not included in current FTD criteria, were common. These symptoms were further analysed in an extended neuropathologically verified cohort (paper III, IV) and both symptom categories were found in about 1/3 of all cases. There was no clear correlation with protein pathology. Psychotic symptoms correlated strongly with right-predominant brain pathology. Clinical misdiagnosis, often psychiatric, was especially common among young patients and in those with psychotic symptoms. Our findings highlight the clinical importance of recognizing symptoms not included in current criteria to achieve a better understanding of these phenomena and to improve diagnostics.