Published on: March 26, 2013
by Cole Petrochko for MedPage Today:
Women who had surgically induced menopause at an early age saw a decline in cognitive function and possible signs of Alzheimer’s disease pathology, researchers reported here.
Among women who had surgically induced menopause, younger age was significantly tied to declines in episodic memory (P=0.0003), semantic memory (P=0.0022), and global cognition (P=0.0007) compared with women who had natural menopause, according to Riley Bove, MD, of Harvard Medical School in Boston, and colleagues.
Younger age at surgical menopause was also significantly associated with global Alzheimer’s disease pathology (P=0.038) and neuritic plaques (P=0.013), Bove said at the meeting of the American Academy of Neurology. However, no significant association was seen with incident Alzheimer’s disease (P=0.093).
Bove noted that estrogen was neuroprotective in animals models and that prior studies had shown that “loss of estrogen associated with early age at menopause may increase risk of cognitive decline, especially in surgical menopause.”
Her group studied the effects of age at surgical menopause on cognitive decline through measures of longitudinal changes in cognition, Alzheimer’s disease diagnosis risk, and neuropathologies related to Alzheimer’s in a combined population of 1,837 women across two cohorts.
One cohort was the Memory and Aging Project (MAP), which analyzed older men and women in assisted living facilities, while the second cohort was the Religious Orders Study (ROS), which looked at Catholic priests, nuns, and brothers.
The study samples included 91% non-Hispanic white participants, 33% of whom had undergone surgical menopause. All patients were free of dementia at baseline. The cohorts also looked at demographic information, baseline reproductive history, annual cognitive status, and a neuropathologic evaluation at autopsy.
The researchers analyzed longitudinal measures of five cognitive domains (episodic, semantic, and working memory; visuospatial ability; and perceptual speed) and global cognition, neuropathologic measure from brain samples obtained at death, and clinical diagnosis of Alzheimer’s disease. They also reviewed associations between age at menarche and menopause, number of cycling years, and use and duration of hormone replacement therapy (HRT).
Measures were adjusted for age, education, smoking, and study, and were stratified by menopause status.
“Early age at menopause was associated with faster decline in semantic memory, episodic memory, and global cognition,” they wrote. Working memory, visuospatial ability, and perceptual speed were not significantly associated with cognitive decline, nor was natural menopause.
In addition to an association with global Alzheimer’s pathology and neuritic plaques, age at menopause in surgical menopause had a trend toward pathologic diagnosis of Alzheimer’s (P=0.053). It was not associated with neurofibrillary tangles or diffuse plaques, nor was it associated with risk of clinical Alzheimer’s disease diagnosis.
There was no significant effect of HRT on cognitive decline with ever versus never or duration of use, “even when hormone replacement therapy was initiated within 5 years of menopause.”
Duration of HRT was associated with slower decline in global cognition (P=0.037).
“Our findings support a growing literature on the impact of surgical menopause on cognitive decline function, and add granularity to these outcome measures,” Bove said, adding that future studies should include an ongoing look at modifying factors, such as HRT.
Bove also noted that their study was limited by patients who did not have dementia at baseline, which may represent an exclusion bias. Additional limitations included cognitive outcomes that were weighted towards memory; self-reporting by participants, retrospective, limited reproductive histories; and unlisted covariates, such as body mass index.