Publications

BACKGROUND

Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia.

OBJECTIVE

To compare demographic characteristics of patients in the 3 FTLD subgroups.

DESIGN

We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany.

RESULTS

The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses.

CONCLUSIONS

These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses.

Individuals with Down syndrome (DS) are at a high risk for developing Alzheimer disease (AD) after the age 40; however, low levels of intellectual functioning, coupled with impaired language ability, confound the detection of AD. Comparative neuropsychological tests developed in animal models of aging and cognition do not require intact language function and can be useful for detecting changes in cognition. Experimental paradigms used to detect age-dependent cognitive deficits in animal models were applied in the present study to measure cognitive function in a group of 20 adults with DS ranging in age from 22 to 58 years. Object discrimination, reversal learning, and spatial and object memory were administered using a modified Wisconsin General Testing Apparatus and reinforcement (penny rewards). When considering age as the only clinical variable to parallel the animal studies, age was significantly correlated with performance on object memory and marginally related to performance on reversal learning and spatial memory. However, when evaluating multiple clinical variables including age, a measure of intellectual ability (FSIQ), scores on the Dementia Questionnaire for Persons with Mental Retardation (DMR), and gender using regression analysis, scores on the DMR were the best predictors of errors of reversal learning, whereas FSIQ was the best predictor of performance on object memory. These results suggest that while age may be related to performance on learning and memory tasks, other clinical variables may be stronger predictors of performance in adults with DS. These changes may reflect prefrontal and medial temporal lobe dysfunction that is associated with the development of AD pathology in DS.