Evidence for Using Sex-Specific Cut-Off Scores to Diagnose Mild Cognitive Impairment

Mild cognitive impairment (MCI), which progresses to Alzheimer’s disease (AD) within 5 years for approximately half of those diagnosed, is identified when an individual’s score is below established cut-off scores on cognitive tests. It has been suggested that because women, on average, score higher on the verbal memory component of these tests, women and men should have different cut-off scores for diagnosis. This hypothesis is supported by new research published in Neurology. 

In a study of 985 individuals from Alzheimer’s Disease Neuroimaging Initiative, 120 women (26%) and 239 men (45%) were diagnosed with MCI using cut-off scores that were not sex specific. In contrast, when sex-specific scores were used, the number of women diagnosed increased to 165 (36%), and the number of men diagnosed decreased to 184 (35%).

In women diagnosed with MCI only when sex-specific score cut-offs were used, imaging biomarkers of AD showed more advanced AD pathology than in those who were not diagnosed with MCI. Similarly, in men diagnosed with MCI using the nonspecific cutoff but not the sex-specific cutoff, AD brain imaging biomarkers were more similar to men without MCI than to men with MCI.

“If these results are confirmed, they have vital implications,” said study author Erin E. Sundermann, PhD, of the University of California, San Diego. “If women are inaccurately identified as having no problems with memory and thinking skills when they actually have mild cognitive impairment, then treatments are not being started and they and their families are not planning ahead for their care or their financial or legal situations. And for men who are inaccurately diagnosed with mild cognitive impairment, they can be exposed to unneeded medications along with undue stress for them and their families.”

Sundermann said the results also have implications for research, if they are confirmed. “When the typical average cut-off scores are used for diagnosis, women might respond less to treatments in a clinical trial than men because they are at a more advanced stage of the disease, while men might not respond because some of them do not actually have MCI,” she said. “These combined factors would result in research that reduces the estimate of how well treatments work for both men and women.”

The cognitive measure used in this study was the Rey Auditory Verbal Learning Test in the Mayo Clinic Study of Aging and most participants had high levels of education, a potential source of bias. Biomarkers for AD pathology included hyperphosphorylated tau/β-amyloid (Aβ) levels in cerebrospinal fluid (CSF), cortical Aβ deposition, and APOE ε4 frequency.