Frontotemporal dementia progresses to death faster than Alzheimer disease.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a common cause of non-Alzheimer dementia, but its natural history and the factors related to mortality in affected patients are not well understood. METHODS: This retrospective, longitudinal study compared survival in FTLD (n = 177) with Alzheimer disease (AD; n = 395). Hazards analysis investigated the contribution of various demographic, neuropsychiatric, and neuropsychological variables and associated neurologic and neuropathologic findings. RESULTS: The frontotemporal dementia (FTD) subtype of FTLD progressed faster than AD (median survival from retrospectively determined symptom onset, 8.7 +/- 1.2 vs 11.8 +/- 0.6 years, p < 0.0001; median survival from initial clinic presentation, 3.0 +/- 0.5 vs 5.7 +/- 0.1 years, p < 0.0001). Survival was similarly reduced in the related conditions corticobasal degeneration and progressive supranuclear palsy. Survival in the semantic dementia subtype of FTLD (11.9 +/- 0.2 years from onset and 5.3 +/- 0.4 years from presentation), however, was significantly longer than in FTD and did not differ from AD. Hazards analysis to determine factors affecting survival in FTLD showed no effect of age at onset, sex, education, family history, or neuropsychiatric profile. Among neuropsychological measures examined, impaired letter fluency had a significant association with reduced survival. Associated ALS significantly reduced survival in FTLD. The presence of tau-positive inclusions was associated with the slowest progression. CONCLUSIONS: Frontotemporal lobar degeneration progresses more rapidly than Alzheimer disease, and the fastest-progressing cases are those with the frontotemporal dementia clinical subtype, coexisting motor neuron disease, or tau-negative neuropathology.

Evaluation of predictors of mortality in frontotemporal dementia-methodological aspects.

OBJECTIVES: To retrospectively evaluate pre-diagnostic clinical features (predictors) of mortality in frontotemporal dementia (FTD). The main aim was to investigate if there were indications against interpreting missing data as signs of absence. MATERIAL AND METHODS: 96 cases with FTD, here defined as Dementia in Pick's disease according to ICD-10. The predictors were behavioural/psychiatric features, language impairment and neurological deficits up to the date of diagnosis. Each predictor was rated as present (Yes), absent (No) or not recorded (Missing), and evaluated according to its distribution and mortality pattern: if a feature was not recorded because it was absent, the mortality of the Missing and the No-category should hypothetically be close. Statistical methods included Kaplan-Meier survival curves and Cox regression analyses. RESULTS: Neurological deficits and language impairments were frequently recorded as present or absent, while non-recordings were more prevalent among the behavioural/psychiatric features. Some features were excluded as predictors because they showed too little variation. Analyses of the survival pattern indicated that in some features, the observations of the Missing-category could be interpreted as absence of the symptoms. In other features these observations had to be regarded as truly missing. CONCLUSIONS: In the retrospective evaluation of predictors of mortality a method for treating missing data was applied. The interpretation of non-recordings as signs of absence was supported by the analyses of the survival patterns in some of the studied features. However, the study underscores the importance of systematic estimations of pre-diagnostic clinical features in dementia.

Predictors of mortality in frontotemporal dementia: a retrospective study of the prognostic influence of pre-diagnostic features.

OBJECTIVES: To find associations between predictors and survival in frontotemporal dementia (FTD). METHODS: 96 patients with FTD, here defined as Dementia in Pick's disease, were studied. The predictors included psychiatric/behavioural features, language impairment and neurological deficits present up to the time of diagnosis. The influence on mortality was studied by means of Cox regression analyses. RESULTS: Most of the behavioural/psychiatric features were associated with longer survival. Among these features, anxiety and suicidal ideation were associated with a statistically significant decreased mortality. Semi-mutism/mutism and neurological deficits were associated with a statistically significant increased mortality. Analyses of the dementia-specific mortality strengthened the already significant results and revealed dysphagia as significantly related to increased mortality. CONCLUSIONS: Two groups of predictors with different influence on survival were identified in FTD. Most behavioural/psychiatric features were associated with longer survival. These features may indicate a slower disease progress and a better preserved cerebral function. By contrast, semi-mutism/mutism, neurological deficits and dysphagia were associated with shorter survival, indicating an aggressive, degenerative process.

Quantification of pathological lesions in the frontal and temporal lobe of ten patients diagnosed with Pick's disease.

The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick's disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.