Variations of the Phenotype in Frontotemporal Dementias
To provide better care for patients, physicians most often seek to determine the cause of symptoms by recognizing a clinical phenotype and then relating that phenotype to known disease mechanisms, including genetic variations and pathology. This approach has been particularly difficult with frontotemporal dementias (FTD), because of the diversity and continuous evolution of its behavioral, language and cognitive symptoms. Recent systematic clinical-pathological observations have resulted in proposed clinical criteria for FTD, but accurate diagnosis remains challenging and, in clinical practice, the phenotype of FTD can easily be confused with other disorders.
Positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) can aid in the recognition of clinical phenotype and explore disease mechanisms. We reviewed the results of FDG-PET in 19 patients who subsequently had FTD confirmed at postmortem examination, including one with a known tau gene mutation. A comparison of scans from normal elderly controls with scans of patients with pathologically confirmed Alzheimer's disease (AD) demonstrates that FTD causes a distinctive pattern of hypometabolism, with considerable individual variability within this general pattern. FTD consistently causes predominant hypometabolism in frontal association, anterior cingulate, and anterior temporal regions, but the involvement of each region is variable and can be either symmetric or asymmetric. As the illness progresses, glucose hypometabolism becomes more pervasive, extending into regions characteristically affected early in AD. Although FDG-PET abnormalities accurately reflect clinical phenotype, neither pathological diagnosis nor genotype reliably predicts the variations observed in the pattern of glucose hypometabolism in FTD.
KeywordsMotor Neuron Disease Frontotemporal Dementia Progressive Supranuclear Palsy Glucose Hypometabolism Cerebellar Diaschisis
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