Neurology and Women’s Health, Part 3: Alzheimer’s disease

Neurology and Women’s Health, Part 3: Alzheimer’s disease

Monday, March 26, 2018

Women bear most of the burden of Alzheimer’s disease, not only making up most of the patients with the condition but also doing most of the demanding work of caring for Alzheimer’s patients.

Kim Johnson, MD, a neurologist at our Morreene Road Memory Disorders Clinic, treats these patients on a daily basis. In our third entry in our “Neurology and Women’s Health” series, she discusses possible reasons why women are more vulnerable to Alzheimer’s, the links between Alzheimer’s disease and mental illnesses and depression, and the economic, physical, and emotional tolls of being a caregiver. Johnson also discusses the progress we’ve seen in identifying Alzheimer’s disease, how women can reduce their risk for developing it, and large-scale efforts to prevent or delay the condition.

Two out of three seniors with Alzheimer’s disease are women. What makes women more vulnerable to this disease?
We are unsure whether female gender itself is actually a risk for developing Alzheimer’s disease. We know more women have Alzheimer’s disease than men. This may be because older age is the greatest risk factor for Alzheimer’s disease and women live longer than men. Also cardiovascular disease is a risk factor for Alzheimer’s disease and of people with cardiovascular disease, more men in mid-life die than women. So men who survive to age 65 and over may be healthier with less Alzheimer’s disease risk than women over age 65. Another factor may be education. We know that low education is a risk factor for dementia and more women may have Alzheimer’s disease at this time due to lower educational attainment in women who are over age 65.

However, we are learning that there may be an increased risk based on gender and genetic risk as we do more research on possible genetic and metabolic causes for Alzheimer’s disease. A 2017 study in JAMA Neurology looking at 57,000 patients ages 55 to 85 compiled from 27 research studies shows women ages 65 to 75 with one copy of the apoE4 allele, the main genetic risk factor for late onset Alzheimer’s disease, have increased risk for developing Alzheimer’s disease compared to men and have an increased chance of mild cognitive impairment between the ages of 55 to 70.

Interestingly, there were no differences between the sexes in patients who had two copies of the apoE4 allele. There are also studies showing the progressive loss of estrogen associated with female aging may have interactions with insulin and brain glucose metabolism and may lead to increased cases of sporadic or non-genetic associated Alzheimer’s disease. The hypothesis is that the loss of estrogen could increase inflammation and loss of synapses between nerve cells making the female brain more vulnerable to Alzheimer’s disease. Overall, the main take away point is that there are still many uncertainties regarding sex differences and more research is needed.

Are there any other ways that symptoms or the course of illness differ for women than they do for men?
A recent article in Lancet Neurology in 2016 summarizes differences that have been discovered in the course of Alzheimer’s presentation between men and women. Among women and men with Alzheimer’s disease who are positive for the apoE4 allele, women demonstrate more severe behavioral disinhibition. On MRI scans among patients with Alzheimer’s disease, women have faster progression of hippocampal atrophy than men; however, men have more periventricular white matter disease.

Women live longer than men with Alzheimer’s disease and have more affective symptoms and disability. Men show more aggressive behavior and have more comorbid medical conditions than women. There is some evidence that women with Alzheimer’s disease treated with the acetylcholinesterase inhibitors donepezil and rivastigmine have less cognitive decline compared to men. This was thought to be due to the effects of an estrogen receptor.

Depression and other mental illnesses often either co-exist with Alzheimer’s disease and dementia, or present similar symptoms. How can we improve the way to prevent and alleviate these conditions among older women?

We know that having depression or a history of depression increases the risk for Alzheimer’s disease. There is a link between the number of depressive episodes in a lifetime and risk of dementia. Therefore, treating depression with therapy or medications should be a public health priority. Depression can also arise after a dementia diagnosis. Ensuring patients over age 65 with and without dementia stay active socially in the community is important. Social isolation is associated with both Alzheimer’s disease risk and depression.

Treating depression with therapy or medications could delay the onset of dementia in select patients. A study earlier this year in the American Journal of Psychiatry showed that treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant for greater than 4 years in patients with mild cognitive impairment and a history of depression delayed progression to Alzheimer’s dementia by approximately 3 years.

Women are also almost three times more likely than men to care for a family member or loved one with Alzheimer’s disease. What consequences does this burden have for caregivers? What can be done do alleviate this burden?
Sixty to seventy percent of caregivers are women and we know that caregivers are under increased stress. Several studies show adverse effects of caregiving on personal health and economic factors. A survey cited in The Shriver Report: A Woman’s Nation Takes on Alzheimer’s shows that all caregivers have 8% higher health care costs than non-caregivers. Sixty two percent of caregivers have increased emotional stress and 40% of caregivers develop significant depression or anxiety. Specifically, three quarters of women caregivers express concern over their ability to maintain their own health.

Women caregivers are especially vulnerable to economic effects. 19% of women caregivers have to quit work due to caregiving demands and 20% transition from full time to part time work whereas the same is not true for men. Only 3% of male caregivers transition from full time to part time work. Caregiving is not easy, regardless of sex but we see higher numbers of women as caregivers which has more effects on their health and economic well-being as a whole.

What steps, if any, can women (and men) take to reduce their likelihood of developing Alzheimer’s disease or dementia?
Recent research studies point to the importance of prevention starting in mid-life and possibly at birth. The invisible effects of preclinical Alzheimer’s disease are occurring decades before symptoms occur. To prevent Alzheimer’s disease women and men should strive for healthy lifestyle with ongoing physical and cognitive activity, a healthy diet and adequate leisure time. The Lancet, a British medical journal, published a review of dementia in late 2017. They found that 35% of all dementias are attributable to low education, midlife hypertension, midlife obesity, diabetes, smoking, hearing loss, late-life depression, physical inactivity and social isolation. Epidemiologic studies are showing that controlling blood pressure and keeping blood glucose consistently in a normal range is important to preventing Alzheimer’s disease.

A Mediterranean diet, high in vegetables, fruits, rice, whole grains, olive oil and low in meats especially red meat has been shown to decrease progression of amnestic MCI to Alzheimer’s compared with other diets. Physical exercise, intellectual stimulation or leisure activities in high amounts over a lifetime are associated with reduced risk of dementia. Improved socioeconomic status during the gestational period and early childhood is protective for late life dementia risk. So it seems that lifestyle choices and habits beginning before birth and established throughout the lifespan may reduce the likelihood of developing Alzheimer’s disease.

What’s the most hopeful development that you’ve seen in how we treat or understand Alzheimer’s disease since you started treating people with this condition?
The discovery of the biomarkers beta amyloid and tau are important to our understanding of the progression of Alzheimer’s disease. The overarching mechanism behind the disease is still uncertain; however, we know that beta amyloid is deposited in the brain decades before clinical symptoms occur and once tau appears in the brain neurodegeneration is occurring. We can now see evidence of neurodegeneration on PET scans.

Knowing that signs of Alzheimer’s disease show up in the brain decades before cognitive decline occurs hopefully will lead to increased prevention strategies enacted on a global health scale and increase quality of life. Alzheimer’s disease is a global public health problem and expected to increase in high income countries and greatly increase in low income countries over the next 50 years. We know that people with higher cognitive reserve from increased education develop dementia more slowly than people without this reserve. This points to the importance of education over the life span, especially early childhood education. This knowledge can lead to global health initiatives to increase education, accessible quality healthcare, physical exercise and improve diet and nutrition.

Another hopeful development is that the importance of diagnosing Alzheimer’s disease accurately and early is being realized by society at large. It allows patients to make their own decisions and plan for their future while they are still able and helps families understand patient’s behaviors. The certainty of a diagnosis can relieve anxiety when patients and families know something is wrong with memory and cognition. Interventions to delay the progression of disease and increase support for patients and families can reduce cognitive and behavioral symptoms.

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