UCSB and UCSF identify 16 blood proteins in menopause linked to brain aging and dementia risk
In blood samples of women before, during and after menopause, 16 proteins tracked menopausal stage more than age. The authors say this is not proof of dementia.
Researchers from the University of California, Santa Barbara (UCSB) and the University of California, San Francisco (UCSF) reported in Nature Medicine that 16 blood proteins were elevated in women before, during and after menopause and are linked to brain aging and dementia risk, according to lomazoma.com. lomazoma.com
lomazoma.comlomazoma.comOpen source ↗ The work was done within the Jacobs Lab Healthy Aging Study and led by Madeline Wood Alexander (Sunnybrook Health Sciences Center), Rowan Saloner and Kaitlin Casaletto (UCSF).
Blood proteins and the menopausal stage
The protein changes were more closely tied to the menopausal stage than to the participants' chronological age. They were confirmed in data from more than 2,800 women in the UK Biobank, where menopause coincided with molecular signs of accelerated aging in several organ systems.
Analyses in four independent cohorts with almost 12,000 older women showed that higher concentrations of these proteins were more often associated with worse cognitive results. In the largest cohort, the protein pattern was associated with a moderately increased risk of Alzheimer's dementia over the following 16 years. The authors stress that the results are neither causal nor direct proof of dementia. Their long-term aim is a blood test as an early warning of dementia risk, comparable to a cholesterol test, and UCSB is launching the Longitudinal Menopause Project.
Hormone therapy and small vessels in a Swedish cohort
A parallel study by Karolinska Institutet with Yale University, the University of Gothenburg and Harvard Medical School, published in Neurology, used brain MRI in 352 cognitively unimpaired women from Gothenburg, mean age 70. Of them, 205 were scanned again after five years. lomazoma.com
lomazoma.comlomazoma.comOpen source ↗ With an average reproductive span of just over 37 years, later menopause was associated with a lower burden of cerebral small vessel disease, while age at first period showed no significant link. Each additional reproductive year corresponded to about 8% lower odds of at least two MRI signs of small vessel disease, though this was unclear after correction for multiple comparisons.
About 73% of participants had used oral contraceptives and around 61% menopausal hormone therapy. Those with hormone therapy experience had 59% lower odds of a higher small vessel burden, which persisted after correction, along with better white matter microstructure. Over five years, hormone use tended to go with slower growth of white matter hyperintensities.
First author Giulia Lorenzon noted that no preventive recommendation can be drawn from the data. Hormone therapy is used to treat symptoms such as hot flashes and night sweats, not to prevent dementia. Hormone use was self-reported without details on dose, type or timing, and the cohort was limited to cisgender women from one Swedish city. The authors also point to no evidence of protection against dementia or stroke, and to oncological and cardiovascular risks.
