Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Platelets of patients with AD exhibit greater unstimulated activation than those of controls. Potential causes of such activation include possible stimulation of platelets by damaged cerebral endothelial cells or platelet activation induced by membrane abnormalities previously reported to be present in platelets of patients with AD. In light of recent evidence that platelets are the principal source of both amyloid precursor protein and beta-amyloid peptide in human blood, it is possible that AD platelet activation may reflect or even contribute to the pathogenesis of the disease.

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We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

Two writing routes (phonological and lexical) have been postulated. We studied four patients who had disruption of the phonological route (ie, inability to write pronounceable nonwords) but with a preserved lexical route. Results showed that the phonological route has two components: segmentation and phoneme-grapheme conversion. Disruption of either function may induce phonological agraphia. The preserved lexical route uses a whole-word mechanism and is strongly affected by semantic factors, such as imageability, emotionality, and grammatic class. Results of CT suggest that a portion of the supramarginal gyrus is the most likely anatomic substrate of phonological agraphia.