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P1–201: Testosterone and risk of dementia in men and women: The Rotterdam Study
Author(s) -
De Jong Frank J.,
Van Oijen Marieke,
Den Heijer Tom,
De Jong Frank H.,
Koudstaal Peter J.,
Hofman Albert,
Pols Huibert A.P.,
Breteler Monique M.B.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.578
Subject(s) - rotterdam study , dementia , medicine , testosterone (patch) , cohort , cohort study , prospective cohort study , population , gerontology , disease , environmental health
a major risk factor for AD but its interaction with cholinergic degeneration is unclear. Objective: To examine the relation between ApoE genotype and cholinergic impairment in AD. Methods: We included 36 patients (mean age 66 years, 23 female, 13 male) with mild to moderate AD according to NINCDS-ADRDA criteria. 15 of them did not carry the ApoE4 allele, 15 were heterozygote, and 6 were homozygote ApoE4 carriers. Cortical AChE activity was studied by the acetylcholine analogue 11C-MP4A PET in 19 of these patients (11 ApoE4 positive, 8 negative). CMRGlc was measured by FDG PET in 35 patients (21 ApoE4 positive, 14 negative). Parametric images of AChE hydrolysis rate constant k3 were generated using a non-invasive technique with a putaminal reference region. Regional changes of CMRGlc were analysed by SPM2. Results: The mean cortical k3 value of the ApoE4 positive subjects (2 homozygotes, 9 heterozygotes) was 0.0459 0.0051 min, which was significantly higher (p 0.05, t-test) than in ApoE4 negative subjects (n 8, 0.0399 0.0066 min). Both groups were comparable with regard to age (63 vs. 65 years) and dementia severity (MMSE 20 vs. 22). In ApoE4 positive patients CMRGlc was reduced mostly in posterior cingulate and temporoparietal cortex, but more in frontal association cortex in the ApoE4 negative group. Conclusions: These results indicate that ApoE4 has no negative effect on AChE activity, suggesting that it does not impair its expression at cholinergic axons and synapses in cerebral cortex. Thus, ApoE4 appears to induce the risk for AD and associated functional impairment in temporoparietal association cortex by pathophysiological mechanisms that are unrelated to degeneration of cholinergic axons.