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

Alzheimers Res Ther. 2019 Dec 26;11(1):109. doi: 10.1186/s13195-019-0565-1.


Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/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 (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau-) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/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 Aβ/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 Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.

Keywords: Hippocampus; Mild cognitive impairment; Sex; Subjective cognitive decline; Verbal memory; Women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Cognition / physiology*
  • Female
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology*
  • Humans
  • Male
  • Memory / physiology*
  • Middle Aged
  • Neuropsychological Tests
  • Organ Size / physiology
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Sex Characteristics
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Peptide Fragments
  • tau Proteins