Are there brain or memory boosters

Menopause and Alzheimer's: How are menopause and dementia related?

Given that menopause and estrogen depletion change the entire body, it is easy to see how a complex set of factors can lead to Alzheimer's and why managing them is key to prevention. Cholesterol regulation is one of the beneficial effects of estrogen on the cardiovascular system: it increases the level of the "good" cholesterol type HDL (high-density lipoprotein) and lowers that of the "bad" LDL (low-density lipoprotein), the causes greasy, waxy deposits to build up in the arteries. The APOE-Gen influences the metabolism of cholesterol and transports it to the neurons. Carrier of e4-General variants therefore naturally have higher LDL cholesterol levels in the blood and thus hardened arteries. The deposits, if loosened by inflammation, can cause "silent strokes," which in turn more than double the risk of Alzheimer's and other forms of dementia.

Sleep and Metabolic Disorders: A Dangerous Spiral

Sleep plays a key role in regulating metabolism, including insulin sensitivity. Women are disproportionately affected by poor sleep, especially during menopause. During a normal night's sleep, the glial cells dispose of beta-amyloid plaques and tau proteins. Sleep deprivation disrupts this process, causing proteins to build up and plaques to form. Sleep is interrupted, which disrupts glucose metabolism, which in turn affects sleep. This creates a dangerous spiral that accelerates neurodegenerative processes. This increases ApoE4-Gen also the risk: It reduces the ability to dissolve or break down amyloid plaques and tangles of rope.

Stress can also affect what happens during menopause. According to a 35-year longitudinal study, the more stressful women in their forties and fifties were exposed to for a month or more, the more likely they were to develop Alzheimer's. When it comes to stress, women are more likely than men to report depression, and this nearly doubles the risk of dementia. Not surprisingly ApoE4- Carriers who have the highest genetic risk of Alzheimer's disease are four times more susceptible to clinical depression than non-carriers. This is possibly due to increased beta-amyloid plaques in those brain regions that are involved in emotion regulation.

In 2019, Brinton and her colleagues published a follow-up to their study of metabolic markers, this time with the APOE-Status as a possible influencing variable. People with a single copy of the ApoE4-Gens, as present in about 25 percent of the US population, are more likely to develop Alzheimer's disease than others and make up about 40 percent of all cases. Affected women usually develop the disease between the ages of 65 and 75 and thus earlier than male gene carriers, presumably because of the dwindling protection of estrogens. People with ApoE4-Gen have on average a higher LDL cholesterol level, more amyloid plaques and tau balls, a smaller hippocampus, and their neural networks break down more. When glucose metabolism in the brain decreases during menopause, the carriers of the e4-Allels may particularly rely on the ketone bodies in the brain for energy.

As in Brinton's earlier study, the group with metabolic problems scored lower on some of the cognitive tests. And this time the analysis also showed that the worse performance was mainly due to ApoE4-Carrier declined. In them, high cholesterol levels and other metabolic markers appear to increase the negative effects of ApoE4leading to early cognitive decline. When the carriers in the cognitively poorer group underwent hormone therapy, both their metabolism and their results on some cognitive tests improved.

Brinton sees that ApoE4- Status but only as a "wake-up call, not a death sentence": After all, many women affected do not develop Alzheimer's. And in their study, the group with optimal metabolism that got the best results on cognitive tests also included carriers of the Alzheimer's gene. Were these women, like the healthy non-carriers, better able to compensate for the "bioenergetic crisis" of menopause? Have you been able to counterbalance other risk factors with your fitness?

At least a third of Alzheimer's cases are related to diabetes, obesity, poor diet and other factors that are preventable and treatable, according to a much-cited finding in the 2017 Lancet. The take-home message is that Maintaining metabolic health also maintains cognitive health, ”concludes Brinton. »You can't change the biological sex, the age or the gene variant - but the metabolic health and thus the risk.«

Mosconi sees it similarly. Everyone, especially women in their forties or fifties, should "know their own metrics," she says, by which she means APOE-Status, metabolic profiles, blood values, even brain scans, especially their gender-specific markers. "I hope brain scans become part of the screening of all middle-aged women (and men), just like we do breast and uterus exams," she says. The mantra is "precaution", a word that was once only rarely paired with Alzheimer's.

Whether hormone therapy should be one of them remains controversial. But precision medicine with its genetic tests and data analysis is moving in this direction, says Brinton. Doctors could soon prescribe precision therapies based on risk markers like this APOE-Status, number of births, menopausal symptoms and other factors. In addition, new variants of hormone therapy are being developed. Karyn Frick, neuroscientist at the University of Wisconsin-Milwaukee, and her colleagues have developed a "stripped-down" version of 17-beta-estradiol: It is supposed to reduce the risk of breast cancer in connection with standard hormone therapy. The drug has not yet been clinically tested in humans, but has shown promise in initial studies in mice. "It worked like a memory booster," says Frick.

For those Alzheimer's cases that cannot be prevented, Brinton's laboratory is developing a drug called Allo based on allopregnanolone, a naturally occurring steroid that stimulates the production of new nerve cells. In experiments on mice, Allo reversed cognitive deficits and increased memory and learning. In a promising phase I clinical study, the volume of gray matter in their hippocampus regenerated in patients with mild dementia, and inflammatory processes in the brain were reduced. Brinton says using a Phase II study funded by the National Institute on Aging ApoE4-Carriers should start in 2020.

Since 2016, the National Institutes of Health has required that clinical research they fund consider gender as a biological variable. The slow progression of Alzheimer's disease means years will pass before women can benefit from new studies on menopause. In the meantime, prevention is still essential: Recommendations include a low-sugar, plant-based diet low in trans and saturated fats, physical activity, little stress, and seven hours of healthy sleep every night, especially for mid-life women. "We women take care of others first and ourselves last," says Brinton. "But we can't put our health on the back burner."