Higher dementia risk in women with prolonged fertility
September 17, 2020
Science Daily/University of Gothenburg
Women with a longer reproductive period had an elevated risk for dementia in old age, compared with those who were fertile for a shorter period, a population-based study from the University of Gothenburg shows.
"Our results may explain why women have a higher risk of developing dementia and Alzheimer's disease than men after age 85, and provide further support for the hypothesis that estrogen affect the risk of dementia among women," says Jenna Najar, a medical doctor and doctoral student at Sahlgrenska Academy who also works at AgeCap, the Centre for Ageing and Health at the University of Gothenburg.
The study, now published in the journal Alzheimer's & Dementia, covers 1,364 women who were followed between 1968 and 2012 in the population studies collectively known as the "Prospective Population-based Study of Women in Gothenburg" (PPSW) and the "Gothenburg H70 Birth Cohort Studies in Sweden" (the H70 studies). The "reproduction period" spans the years between menarche (onset of menstruation) and menopause, when menstruation ceases.
Of the women studied with a shorter reproductive period (32.6 years or less), 16 percent (53 of 333 individuals) developed dementia. In the group of women who were fertile a longer period (38 years or more), 24 percent (88 of 364) developed dementia. The difference was thus 8 percentage points.
The study shows that risk for dementia and Alzheimer's disease increases successively for every additional year that the woman remains fertile. The association was strongest for those with dementia onset after age 85, and the effect was most strongly associated with age at menopause.
These results persisted after adjustment for other factors with an influence, such as educational attainment, physical activity, BMI, smoking, and cardiovascular disease. On the other hand, no association was found between dementia risk and age at menarche, number of pregnancies, duration of breastfeeding, or exogenous estrogen taken in the form of hormonal replacement therapy (HRT) or oral contraceptives.
Several studies have investigated how estrogen in the form of HRT affects dementia risk. Some studies show that dementia risk falls and others that it rises, especially in women who take estrogen late in life.
In the current study Jenna Najar has, instead, investigated the long-term association between factors related to endogenous estrogen and dementia.
"What's novel about this study, too, is that we've had access to information about several events in a woman's life that can affect her estrogen levels. Examples are pregnancies, births, and breastfeeding. Being pregnant boosts estrogen levels tremendously; then they decline once the baby is born, and if women breastfeed the levels fall to extremely low levels. The more indicators we capture, the more reliable our results are," Najar says.
Ingmar Skoog, professor of psychiatry at Sahlgrenska Academy, University of Gothenburg and head of AgeCap, led the study.
"The varying results for estrogen may be due to it having a protective effect early in life but being potentially harmful once the disease has begun."
At the same time, Skoog points out that the duration of women's fertile periods is one risk factor for dementia among many.
Most women whose menopause is delayed do not develop dementia because of this factor alone. However, the study may provide a clue as to why women are at higher risk than men for dementia after age 85, the most common age of onset. Alzheimer's disease, on the other hand, starts developing some 20 years before symptoms of the disorder become apparent.
"Most people affected are over 80 and female," Najar says.
"As a result of global ageing, the number of people affected by dementia will increase. To be able to implement preventive strategies, we need to identify people with an elevated risk of dementia."
https://www.sciencedaily.com/releases/2020/09/200917105419.htm
New diagnostic criteria may enable earlier detection of cognitive impairment in women
Tailoring verbal memory test criteria to patient's sex may improve diagnostic accuracy in mild cognitive impairment
October 9, 2019
Science Daily/University of California - San Diego
Study finds when verbal memory test cut-offs were tailored to patient sex, more female patients and fewer male patients were considered to have amnesic mild cognitive impairment. This could change the way aMCI diagnoses are determined and make it easier to catch the condition in its early stages.
Women make up two-thirds of patients with Alzheimer's disease -- so why is it that women are less likely than men to be diagnosed with its precursor, amnestic mild cognitive impairment (aMCI)? This was the question guiding a new study by University of California San Diego School of Medicine researchers studying how the life-long female advantage in verbal memory performance might be masking early symptoms of dementia in women.
In a study published October 9, 2019 by Neurology®, the medical journal of the American Academy of Neurology, the team studied the data of nearly 1,000 patients who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and found that when verbal memory test cut-offs were tailored to patient sex, more female patients and fewer male patients were considered to have aMCI. This could change the way aMCI diagnoses are determined and make it easier to catch the condition in its early stages.
"The point of the study was to see if we adjusted for this sex difference in verbal memory and made the cut point for impairment more conservative in women, would we be able to detect them earlier in the disease trajectory?" said first author Erin Sundermann, PhD, assistant project scientist in the Department of Psychiatry at UC San Diego School of Medicine. "That's important because currently the interventions that we have are likely most effective in the earlier stages."
Verbal memory includes the ability to remember words, recall stories and memorize verbal information. While it is well established that women show a life-long advantage in verbal memory performance, standard cutoffs for impairment on most verbal memory tests are determined using data gathered across both sexes. Most diagnostic criteria for a dementia diagnosis take several factors into account, like age and education level, but do not often consider sex.
Sundermann and team calculated sex-specific diagnostic criteria by taking the differences in verbal memory performance into account, which led to a more conservative score cut-off for impairment in women. Using the new criteria, about 10 percent of the female patients in ADNI who had previously been considered "cognitively normal" were now classified as aMCI.
What's more, when the scientists looked at biomarkers associated with dementia, they found that these newly diagnosed aMCI cases showed biomarker profiles more similar to those of the other female patients with aMCI than participants who were considered cognitively normal. Conversely, the new criteria for men determined that about 10 percent of men previously considered to have aMCI were now classified as cognitively normal, and, biologically, those men more closely resembled healthy controls than other men with aMCI.
"This suggests that adjusting for sex in verbal memory norms can improve diagnosis in both men and women and can detect women earlier in the disease trajectory and avoid false diagnosis in men that lead to stress and unnecessary treatment," Sundermann said.
This can also lead to improved study design for clinical trials and dementia research, by improving participant criteria and selection, leading to more accurate studies on disease progression and intervention.
https://www.sciencedaily.com/releases/2019/10/191009162435.htm
Risk and progression of Alzheimer's disease differs by sex
July 16, 2019
Science Daily/Vanderbilt University Medical Center
The abnormal accumulation of proteins in the brain is a biological marker for Alzheimer's disease, but the ways in which these proteins spread may help explain why the prevalence of Alzheimer's is higher in women than in men.
A recent study by researchers from the Center for Cognitive Medicine (CCI) at Vanderbilt University Medical Center identified differences in the spread of a protein called tau -- which is linked to cognitive impairment -- between men and women, with women showing a larger brain-wide accumulation of tau than men due to an accelerated brain-wide spread.
The findings were presented at the Alzheimer's Association International Conference July 14-18 in Los Angeles.
Accumulating evidence suggests that tau spreads through brain tissue like an infection, traveling from neuron to neuron and turning other proteins into abnormal tangles, subsequently killing brain cells. Using data from positron emission tomography (PET) scans of healthy individuals and patients with mild cognitive impairment who were enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, CCI researchers constructed in vivo networks modeling tau spread using graph theory analysis.
"It's kind of like reconstructing a crime scene after a crime. You weren't there when it happened, but you can determine where an intruder entered a house and what room they entered next," said Sepi Shokouhi, PhD, assistant professor of Psychiatry and Behavioral Sciences and lead investigator for the study. "The graph analysis does something similar to show how tau spreads from one region to another."
The results of the analysis showed the architecture of tau networks is different in men and women, with women having a larger number of "bridging regions" that connect various communities in the brain. This difference may allow tau to spread more easily between regions, boosting the speed at which it accumulates and putting women at greater risk for developing Alzheimer's disease.
If proven, an accelerated spread of tau in women may indicate a need for sex-specific approaches for the prevention of Alzheimer's disease, including earlier therapies, lifestyle interventions and/or cognitive remediation. More studies are needed to validate the accelerated tau spread model in women.
"Understanding how different biological processes influence our memory is a really important topic. Sex-specific differences in the brain's pathological, neuroanatomical and functional organization may map into differences at a neurobehavioral and cognitive level, thus explaining differences in the prevalence of neurodegenerative disorders and helping us develop appropriate treatments," said Shokouhi.
https://www.sciencedaily.com/releases/2019/07/190716124853.htm