ABSTRACTAlzheimer’s disease (AD) is characterised by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of toxic amyloid-beta protein). Females have worse neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however biological sex can interact with diagnosis (mild cognitive impairment (MCI) or AD) and APOE genotype (number of ε4 alleles), although there are discrepancies between studies. Using the ADNI database, we analysed the effect of sex and APOE genotype (number of ε4 alleles) and sex and diagnosis (cognitively normal (CN), MCI, AD) on cognition (memory and executive function), hippocampal volume, CSF amyloid beta, CSF tau and ptau. More males were diagnosed with MCI but there was no sex difference in those diagnosed with AD, suggesting the progression from CN, MCI to AD may be sex-specific. We found, consistent with some studies, that females had higher levels of CSF tau-pathology that was disproportionately affected by APOE genotype compared to males. These results suggest that sex and APOE genotype effects on AD biomarkers may influence sex differences in incidence and progression of MCI and AD. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Females had better memory (including verbal) scores than males, which may suggest a delay in the onset of cognitive decline or diagnosis.
Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease
