Paid employment could lead to slower later-life memory decline in women, according to a new study looking at how differences in life experiences affect dementia risk.

In the study, presented at the Alzheimer’s Association Internal Conference 2019, a team of researchers from the University of California looked at data from 6,386 women born between 1935 and 1956 in the US who took part in the Health and Retirement Study. The women were asked about their employment, marital and parenthood status each year between the ages of 16 and 50. They also completed memory and thinking tests every two years from the age of 50, for 13.8 years on average.

The researchers created different groups based on the life experience of the women: working non-mothers (518 women), working married mothers (4,450 women), working single mothers (545 women), non-working married mothers (541 women), and non-working single mothers (332 women). They then looked at the difference between these groups in later-life memory decline, adjusting for factors that could influence the results, including practice effects (from the repeating of memory tests), age at study entry, ethnicity, birth region, childhood socioeconomic status and education level.

The team found that the rate of memory decline was similar for working mothers and working non-mothers, but that the fastest rate of memory decline was in non-working women. This suggests that paid employment plays a stronger role in later-life memory decline than family structure.

Dr Jana Voigt, Head of Research at Alzheimer’s Research UK, said: “These preliminary results suggest that paid employment may play an important role in later-life memory decline, but we can’t tell from this study whether the link is causal. The study looked at age-related memory decline, so we don’t know what effect work has on the number of women developing dementia. Unravelling the link between employment and memory decline will help grow our understanding of brain health and the best ways to maintain it.

“While future studies need to explore links between employment and brain health, these initial findings support ongoing efforts to increase the number of women entering or staying in the workforce.”

Verbal memory advantage in women with Alzheimer’s

More women than men are affected by dementia, and in the UK women make up two thirds of those living with the condition. While women can expect to live longer than men, this alone may not explain the difference in the numbers developing dementia, and scientists have been delving deeper into the biological variations that could underlie this effect.

Researchers have previously reported that women outperform men on verbal memory tests, and that this female advantage is apparent at the early stages of Alzheimer’s despite similar levels of disease-related brain changes. To probe this finding further, researchers in the US have studied energy usage in the brain to see if there are differences between men and women.

The team from the University of California looked at data from 1,022 people collected by the Alzheimer’s Disease Neuroimaging Initiative. They looked at brain scans that showed the metabolism of glucose in the brain, which indicates brain activity, and performed verbal memory tests.

They also looked at scans that highlighted the presence of amyloid protein build up in the brain, or tests of spinal fluid for toxic tau, both of which are indicators of Alzheimer’s disease. The researchers grouped people based on the levels of amyloid in the brain and tau in spinal fluid, and looked at differences between the sexes in the energy use in their brains and their performance on the verbal memory tests.

Women outperformed men on the verbal memory tests when amyloid build-up was minimal to moderate, however this advantage was not seen in women with higher levels of amyloid build up. When they looked at energy usage in the brain, the researchers found that women showed higher levels of brain glucose metabolism than men at minimal to moderate levels of amyloid build up.

When the team adjusted for energy usage, the difference in verbal memory scores between men and women all but disappeared, suggesting that the differences in energy usage are a factor in the verbal memory advantage shown by women. This in turn suggests that women may be able to compensate for early Alzheimer’s-related brain changes.

Voigt said this study sheds light on the factors that underlie differences in how men and women show the early symptoms of Alzheimer’s disease.

She added:"Interestingly, despite having similar levels of toxic protein build-up to men, women’s brains showed higher brain activity and better verbal memory. These new findings suggest that women’s brains may be able to compensate for the early damage of Alzheimer’s disease.

“Understanding the biological basis of this female advantage may help refine methods of diagnosis for diseases like Alzheimer’s, to account for sex specific differences and ensure that people with the disease are not slipping through the net.”

Identification of sex-specific differences in Alzheimer’s risk genes

More women live with dementia than men, suggesting that there may be sex-specific risk and protective factors at play. Previous studies have suggested that some genetic variations linked with Alzheimer’s contribute to risk differently in men and women. In this new study, researchers from the University of Miami have looked for additional sex-specific risk genes for Alzheimer’s disease.

The team used data from the Alzheimer’s Disease Sequencing Project whole exome sequencing study, which has data from 5,522 people with Alzheimer’s (56.4% female) and 4,919 people without the disease (59.1% female). They identified genes from this dataset that were linked with Alzheimer’s risk, and then confirmed the link using another dataset – the Alzheimer’s Disease Genetics Consortium Haplotype Reference Consortium, of 9,135 people with Alzheimer’s (60% female) and 9,677 without (60% female).

They used statistical analysis to investigate whether there are sex-specific differences in the risk conferred by the genes they identified. This revealed 73 genes that were associated with Alzheimer’s risk for one sex but not the other. The researchers then looked at which genes have functions relevant to the biology of Alzheimer’s disease, finding genes involved with waste recycling pathways and immune responses.

“We don’t yet know why certain genes are linked with Alzheimer’s risk in one sex and not the other but unravelling this could provide some answers as to why more women are living with dementia than men.”