Does Cognitive Reserve Play a Role in Mild Cognitive Impairment?

Researchers sought to understand sex differences in verbal memory deficits and its relationship to hippocampal volume.

Differences in verbal memory scores in men and women with mild cognitive impairment suggest there is a possible sex-specific cognitive reserve, according to a study published in Neurology.

Accelerated cognitive decline may be related to patients with more cognitive reserve being diagnosed at an advanced stage of Alzheimer’s disease (AD). Historically, women perform better on tasks of verbal memory than men.

Because the hippocampus is involved in verbal memory, Erin Sundermann, PhD, of the Department of Neurology at Albert Einstein College of Medicine in New York, and colleagues sought to understand sex differences in verbal memory deficits and its relationship to hippocampal volume.

The investigators used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) which included healthy participants (n=379), participants with amnestic mild cognitive impairment (aMCI) (n=694), and participants with AD (n=235).  Participants were assessed for hippocampal volume/intracranial volume ratio (HpVR) with MRI and verbal memory with the Rey Auditory Verbal Learning Test (RAVLT).

They researchers found that immediate recall scores within each group and overall were higher for women (P<.05). Likewise, women demonstrated higher delayed recall scores in the control group, the aMCI group, and overall (P<.001).

The investigators also found a significant sex × HpVR interaction for delayed (P=.008) and immediate recall (P=.001) on the RAVLT. In participants with moderate to large HpVR, women also performed better than men.

When stratified by diagnosis, the aMCI group demonstrated a significant HpVR × sex interaction for delayed (P=.006) and immediate recall (P=.0008). In the aMCI group, women with larger HpVR performed better than men on delayed and immediate recall. However, there were no identified sex differences in participants with aMCI and smaller HpVR.

Women in the control group performed better than men regardless of HpVR in both delayed and immediate recall (P=.01). Women in the AD group also performed significantly better than men in immediate recall (P=.004). Further, smaller HpVR in participants with AD was associated with worse delayed recall irrespective of sex (P=.001).

“The relationship between verbal memory and HpVR varies by sex; women show an advantage in verbal memory despite minimal to moderate levels of hippocampal atrophy,” the authors wrote. “Findings suggest that women might show a sex-specific cognitive reserve in the domain of verbal memory.”

In an accompanying editorial, Mary Sano, PhD and Sam Gandy, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York and the Veterans Affairs Medical Center in Bronx, New York recognize that the results reiterate previous observations of better cognitive performance by women throughout their lifespan.

However, they suggest that describing this female advantage as cognitive reserve is a “convenient interpretation overly focused on cross-sectional findings that do not fully appreciate the degenerative nature of the disease.”

Ultimately, the results demonstrate the need for accurate and subjective detection methods for cognitive changes in women. 


  1. Sundermann EE, Biegon A, Rubin LH, et al. Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy. Neurology. 2016. doi:10.1212/WNL.0000000000002570.
  2. Sano M and Gandy S. Sex differences in cognition. Does the “fairer sex” need a fairer test? Neurology. 2016; doi:10.1212/WNL.0000000000002573