Better Verbal Memory Skills May Mask Early Signs of Alzheimer Disease in Women

Women display better verbal memory than men in amnestic mild cognitive impairment (aMCI) despite similar levels of brain hypometabolism, according to a new study.

“The lifelong advantage that females show over males in verbal memory might represent a form of cognitive reserve that delays verbal memory decline until more advanced pathology, as indexed by temporal lobe glucose metabolic rates (TLGluMR),” the researchers said.
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The investigators examined 390 controls and 672 participants with aMCI and 254 with Alzheimer disease (AD) dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who completed the Rey Auditory Verbal Learning Test (RAVLT) and [¹⁸F]-fluorodeoxyglucose–PET. They conducted cross-sectional analyses using linear regression to examine the sex by TLGluMR interaction on RAVLT performance in the overall sample and within diagnostic groups adjusting for age, education, and APOE ε4 genotype.

Across groups, female sex and higher TLGluMR and their interaction were associated with better verbal memory. The female advantage in verbal memory varied by TLGluMR such that the advantage was greatest among individuals with moderate to high TLGluMR and was minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed this interaction was driven by the aMCI group. The researchers found the interaction not significant in the control and AD dementia groups.

“Impairment on clinical tests of verbal memory is key to diagnosing Alzheimer’s and MCI,” said lead study author Erin E. Sundermann, PhD, project scientist at the University of California, San Diego, who conducted the research while at Albert Einstein College of Medicine in New York City. “These clinical tests have established score cut-points that are used to distinguish impaired from unimpaired performance and many of these cut-points do not take sex into account.”

“It is important for health care providers and the clinical tests used in diagnosis to account for the differences in verbal memory performance in men and women. If sex isn’t taken into consideration, then health care providers risk diagnosing women with Alzheimer’s or MCI later in the disease process compared to men when the potential for treatment becomes more limited.”

Their next step is to create these sex-adjusted cut-points on the verbal memory test used in the ADNI and apply that to the ADNI population in order to see how diagnoses change. “Our prediction would be that more women will be diagnosed with MCI after applying sex-adjusted cut-points,” she concluded.

—Mike Bederka

Reference:

Sundermann EE, Maki PM, Rubin LH, Lipton RB, Landau S, Biegon A; Alzheimer's Disease Neuroimaging Initiative. Female advantage in verbal memory: evidence of sex-specific cognitive reserve [published online October 5, 2016]. Neurology. doi:10.1212/WNL.0000000000003288.