Dr. Jessica Klusek, along with co-authors Gierman, Fairchild, Benitez, Berry-Kravis, and Mailick, published a new research article in the Journal of Alzheimer’s Disease titled: “Cognitive dysfunction in women with the FMR1 premutation during midlife: The LASSI-L reveals curvilinear CGG-dependent risk buffered by college education.”

Women with the FMR1 premutation are known to have a higher chance of experiencing certain mental and physical health challenges, including depression, anxiety, sleep problems, and early menopause. It has also been estimated that approximately 16% of women with the premutation later develop fragile X–associated tremor/ataxia syndrome (FXTAS), a neurodegenerative condition thought to emerge after age 60. However, more subtle changes in memory and thinking might begin earlier. However, it has remained unclear whether more subtle cognitive changes might begin earlier in adulthood.

To better understand this, the research team studied 88 women with the premutation and 84 women without the premutation, all between the ages of 30 and 55. Participants completed a specialized memory test called the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), which is designed to detect very early and subtle changes in memory.

Results showed that women with the premutation showed subtle difficulty managing memory interference and made more “intrusion” errors, meaning they recalled incorrect but related words. These patterns are similar to very early memory changes sometimes observed in preclinical Alzheimer’s disease (though it should be noted the results do not suggest that these women have Alzheimer’s). About 10% of women with the premutation (versus 2% without) showed memory scores that may indicate elevated cognitive risk in midlife. Notably, these differences were observed in women as young as their 30s and 40s – decades before the typical onset of FXTAS.

Encouragingly, college education appeared to play a protective role. Women with the premutation who had earned a college degree performed similarly to women without the premutation, while those without a college degree showed greater memory difficulty. This protective effect was strongest among women with mid-range CGG repeat lengths (approximately 80–100 repeats).

Together, these findings highlight midlife as a critical window for cognitive monitoring in women with the premutation and suggest that education and other life experiences may help reduce risk – particularly for certain genetic subgroups. The results provide important direction for identifying women who may benefit from closer clinical monitoring and early preventive strategies.

To read the full article, click here!

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