“…In conclusion, our results show a robust gender difference in the rate of change in ADAS-Cog and CDR-SB in MCI subjects, with women declining at much higher rates than men. These findings support prior calls [1] , [3] , [4] , [5] , [10] , [11] , [12] , [36] to make gender-specific research in AD a priority. Research in context Systematic review: The authors reviewed the literature using traditional sources (PubMed, conference abstracts).…”
INTRODUCTION
This study examined whether, among subjects with mild cognitive impairment (MCI), women progressed at faster rates than men.
METHODS
We examine longitudinal rates of change from baseline in 398 MCI subjects (141 Females, 257 Males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1), followed for up to 8 years (mean 4.1±2.5 years) using mixed effects models incorporating all follow ups (mean 8±4 visits).
RESULTS
Women progressed at faster rates than men on ADAS-Cog (p=0.001) and CDR-SB (p=0.003). Quadratic fit for change over time was significant for both ADAS-Cog (p=0.001) and CDR-SB (p=0.004), and the additional acceleration in women was 100% for ADAS-Cog and 143% for CDR-SB. The variability of change was greater in women. The gender effect was greater in ApoE4 carriers.
DISCUSSION
Women with MCI have greater longitudinal rates of cognitive and functional progression than men. Studies to confirm and uncover potential mechanisms appear to be warranted.
“…In conclusion, our results show a robust gender difference in the rate of change in ADAS-Cog and CDR-SB in MCI subjects, with women declining at much higher rates than men. These findings support prior calls [1] , [3] , [4] , [5] , [10] , [11] , [12] , [36] to make gender-specific research in AD a priority. Research in context Systematic review: The authors reviewed the literature using traditional sources (PubMed, conference abstracts).…”
INTRODUCTION
This study examined whether, among subjects with mild cognitive impairment (MCI), women progressed at faster rates than men.
METHODS
We examine longitudinal rates of change from baseline in 398 MCI subjects (141 Females, 257 Males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1), followed for up to 8 years (mean 4.1±2.5 years) using mixed effects models incorporating all follow ups (mean 8±4 visits).
RESULTS
Women progressed at faster rates than men on ADAS-Cog (p=0.001) and CDR-SB (p=0.003). Quadratic fit for change over time was significant for both ADAS-Cog (p=0.001) and CDR-SB (p=0.004), and the additional acceleration in women was 100% for ADAS-Cog and 143% for CDR-SB. The variability of change was greater in women. The gender effect was greater in ApoE4 carriers.
DISCUSSION
Women with MCI have greater longitudinal rates of cognitive and functional progression than men. Studies to confirm and uncover potential mechanisms appear to be warranted.
“…Estrogen may reduce aggregation of Ab, so the decrease in estrogen during menopause might contribute to a rise in Ab. 33 Interestingly, although others have reported higher amyloid in persons with higher educational attainment, 1 we did not confirm this association in our study. Further, our own work in ARIC has suggested that level of educational attainment does not influence rate of cognitive decline itself, but rather raises the absolute level of scores, a manifestation of cognitive reserve, and might delay the age at which an individual passes below a threshold and is diagnosed with dementia.…”
Objective: To evaluate differences in amyloid deposition in a community-based cohort without dementia by age, sex, race, education, and APOE e4 allele status.
Methods:Recruited from the longitudinal Atherosclerosis Risk in Communities study, 329 participants without dementia, ages 67-88 years, were imaged using florbetapir PET at 3 US community sites (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi). Standardized uptake value ratios (SUVRs) were calculated; global cortical SUVR .1.2 was evaluated as the primary outcome. Age, race, sex, education level, and number of APOE e4 alleles were evaluated in multivariable models including vascular risk factors, brain white matter hyperintensity and total intracranial volume, and cognitive status.Results: A total of 141 of the participants (43%) were black. In multivariable models, odds of elevated SUVR was increased in participants with increasing age (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.01-2.65 per 10 years of age) and black race (OR 2.08, 95% CI 1.23-3.51) but did not differ by educational level. Each e4 allele was associated with increased odds of elevated SUVR (OR 2.65, 95% CI 1.61-4.39).Conclusions: In this community-based cohort without dementia, florbetapir uptake is associated with older age and APOE genotype. Black race was associated with higher SUVR, after adjusting for demographics, vascular risk factors, cognitive status, white matter hyperintensity volume, and APOE genotype, with effect sizes nearing those seen for APOE e4. Replication of these findings is needed in other cohorts, and reasons for and consequences of these observed differences by race warrant further study. The prevailing hypothesis behind the pathophysiology of Alzheimer disease (AD) focuses on the accumulation of brain amyloid in b-amyloid (Ab) plaques as a critical mechanism. Use of PET ligands that bind to Ab allows for the evaluation of Ab in persons with or without clinical symptoms. Although a recent meta-analysis reported positive amyloid scans in 10% of healthy 50-to 90-year-old participants, and in 27% of similarly aged adults with mild cognitive impairment (MCI), 1 few studies in persons of European extraction 2,3 have evaluated patterns of Ab deposition using PET, and none in black participants, to our knowledge. Using Ab imaging in a biracial cohort would allow further exploration of racial disparities in dementia etiology.Dementia is more prevalent in blacks than in whites, 4-6 although AD-type neuropathologic findings are found on autopsy with equal prevalence in both groups. 7,8 Thus, a larger component
“…These results are salient because they suggest that diosmin may be particularly effective in treating female AD patients by targeting the most toxic form of Aβ. AD has been shown to affect female AD mouse models and patients more than males (Lin and Doraiswamy, 2014) and finding a therapy for the treatment of females with AD has been an important challenge. In addition, our results indicate that these prophylactic effects of diosmin are mediated by increased levels of TPRC6, which has been shown to specifically inhibit APP cleavage by γ-secretase and reduce Aβ production, without affecting Notch cleavage (Wang, Lu, 2015).…”
Naturally-occurring bioactive flavonoids such as diosmin significantly reduces amyloid beta (Aβ) associated pathology in Alzheimer’s disease (AD) mouse models. In the present study, oral administration of diosmin reduced cerebral Aβ oligomer levels, tau-hyperphosphorylation and cognitive impairment in the 3xTg-AD mouse model through glycogen synthase kinase-3 (GSK-3) and transient receptor potential canonical 6-related mechanisms. Diosmetin, one major bioactive metabolite of diosmin, increased inhibitory GSK-3β phosphorylation, while selectively reducing γ-secretase activity, Aβ generation, tau hyperphosphorylaion and pro-inflammatory activation of microglia in vitro, without altering Notch processing. Therefore, both diosmin and diosmetin could be considered as potential candidates for novel anti-AD therapy.
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