Cognitively normal women with Alzheimer's disease proteinopathy show relative preservation of memory but not of hippocampal volume

Background We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (A beta/P-tau) on verbal memory and hippocampal volumes. Methods We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer's disease (AD) proteinopathy (CSF Ass/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results Amyloid-positive (A beta/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (A beta/P-tau-) CN women. In contrast, A beta/P-tau+ CN men (men with preclinical AD) showed poorer memory than A beta/P-tau- CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and A beta/P-tau on other measures of cognition or on hippocampal volume. Conclusions CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of A beta/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.