Women who use a popular menopause treatment later in life may be at a higher risk of Alzheimer’s disease, a study suggests.
Researchers found women who took hormone replacement therapy (HRT) in their sixties were at a much higher risk of dementia in their 70s.
These women had higher levels of a plaque linked to Alzheimer’s in their brains compared to their peers who never took the drug.
Younger women who stopped taking HRT in their 50s and early 60s did not show the same Alzheimer’s risk. The researchers say it suggests that women should not be prescribed HRT if they’ve been menopausal for over 10 years without treatment.
Dr Gillian Coughlan, a neurologist at Mass General Brigham Hospital in Boston and first author of the study, said: ‘Our data indicate that HT may influence tau accumulation as a function of age, with implications for cognitive decline.
‘We hope that our study will help to inform AD risk discussions relating to women’s reproductive health and treatment.’
The women who took HRT later had higher levels of a protein called tau in certain brain regions responsible for memory and cognition.
Tau is a key factor in the genesis of Alzheimer’s disease, which affects nearly seven million Americans annually, around two-thirds of whom are women.
Tau proteins help maintain the structure and function of brain cell networks, enabling communication between cells. When this wiring is damaged, tau proteins become loose and break away, leading to communication breakdowns.
The damaged tau proteins clump together, forming toxic tangles in the brain.
Over time, these tangles kill brain cells, contributing to the cognitive decline seen in Alzheimer’s disease.
The study was published in the journal Science Advances.
Researchers from Mass General Brigham, an integrated health care system that includes Harvard Medical School-affiliated hospitals and other health care facilities, recruited 146 women, with an average age ranging from 51 to 89, at the beginning of the study.
Half had used HT an average of 14 years prior and the other half never used it at all.
They had PET scans checking for amyloid beta, another protein believed to be responsible for the onset of Alzheimer’s, over an average of four and a half years.
The women also underwent PET scans to look for tau tangles over three and a half years.
Women over 70 who used hormone therapy showed faster tau buildup in brain areas linked to memory and recognition compared to non-users of the same age.
The tau accumulation was linked to cognitive decline and was only seen in HT users, suggesting that tau buildup might contribute to their cognitive issues.
In women under 70, HT use appeared to protect against tau buildup in the area responsible for memory consolidation, with no significant cognitive decline in non-users.
Researchers are unsure if the faster tau buildup in older HT users is due to when they started therapy or if older individuals naturally show more tau buildup in PET scans.
Women are more likely to have higher levels of tau buildup in brain cells over the course of their lives. This could be driven by an enzyme that lives on the X chromosome, of which women have two copies compared to one in men.
This means more of the enzyme enters women’s brains which inhibits the recycling of tau, leading to more build-up.
The decline in estrogen during menopause is believed to play a major role in the accumulation of tau in women’s brains, likely due to the hormone’s involvement in protecting the brain.
Dr Coughlan said: ‘Our findings add to the evidence that delaying initiation of HT, especially in older women, could lead to worse Alzheimer’s outcomes.
‘We hope that our study will help to inform AD risk discussions relating to women’s reproductive health and treatment.’