Scientists have identified a gene that appears to increase the risk of Alzheimer’s in women, providing a potential new clue as to why more women than men are diagnosed with the disease.
The gene, O6-Methylguanine-DNA-methyltransferase, or MGMT, plays an important role in how the body repairs damage to DNA in both men and women. But researchers did not find an association between MGMT and Alzheimer’s in men.
“It’s a female-specific finding — perhaps one of the strongest associations of a genetic risk factor for Alzheimer’s in women,” said senior study coauthor Lindsay Farrer, chief of biomedical genetics at Boston University School of Medicine.
Two-thirds of the 6.5 million Americans currently living with the devastating brain disease are women, according to the Alzheimer’s Association. It’s a trend that holds true worldwide.
“Women, due to unique genetic risk factors like APOE ε4 and MGMT, and sex-specific risk factors like the sudden reduction in estrogen during the peri-menopause transition, may be in the fast-lane toward the disease, while men are sitting in traffic,” said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Florida Atlantic University’s Schmidt College of Medicine, who was not involved in the study.
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The APOE ε4 gene is considered the strongest risk factor for the future development of Alzheimer’s in people over the age of 65, which is “especially true for women, who are more impacted by APOE ε4 than men,” Isaacson said.
However, many women with APOE ε4 don’t develop Alzheimer’s while women without the gene may still develop the disease.
“Perhaps MGMT is an important missing piece of the risk prediction puzzle for these women, but further studies are necessary,” Isaacson said.
A lucky discovery
The discovery of the new gene’s existence was made in two completely separate groups of people. A team of researchers from the University of Chicago were analyzing the genetic makeup of a small group of Hutterian Brethren women who live communally in rural Montana and South Dakota. Hutterites are a closed population who intermarry within their own ranks and keep extensive genealogical records, making them an excellent choice for genetic research.
“The relatively uniform environment and reduced genetic variation in Hutterites increases our power to find associations in smaller sample sizes than required for studies in the general population,” said senior study coauthor Carole Ober, chair of human genetics at the University of Chicago, in a statement.
When the new association with MGMT popped up in her analysis, Ober reached out to Boston’s Farrer to see if he might help replicate her findings.
Farrer, who was in the midst of a huge genetic analysis of over 10,000 women from the Alzheimer’s Disease Genetics Consortium study, was surprised by the call.
“I told her we’d found the exact same gene in our analysis,” Farrer said. “Two different studies started independently of one another find by serendipity the same gene, which to me adds a lot of confidence that the finding is robust.”
The combined study was published Thursday in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association.
10 potential early signs of dementia
10 potential early signs of dementia
A dementia diagnosis comes after a series of tests of memory, problem-solving, and other cognitive abilities performed by a health care provider. Blood tests, brain scans, and physicals are carried out to help doctors figure out the underlying cause. Dementia is broken down into early, mid, and late stages, with a worsening of symptoms as the condition progresses.
The long-term effects of dementia can be difficult for both those affected and their caregivers, family, and friends, and can include a lack of family recognition, difficulty walking, and significant memory impairment. The afflicted person becomes completely dependent on others for care. Early diagnosis is especially important and can help with planning both at home, with preventive care and other measures such as reminders, and at work. It also enables dementia patients to access clinical trials and available therapies that may improve cognitive functioning and overall quality of life.
Neural Effects consulted the CDC’s list of warning signs for dementia and Alzheimer’s disease to review what adults should look for before seeking an official medical diagnosis. This list may also prove helpful for those who’ve noticed loved ones who are experiencing one or more early signs of dementia.
Memory loss that disrupts daily life
Forgetting recently learned information is one of the earliest signs of dementia. Name recall, as well as remembering important dates and events, becomes difficult for people in the early stages of dementia. Often they need to rely on memory aids, like wall calendars, sticky notes, digital reminders, or help from family members for things like taking medications at the correct time and arriving on the right date to appointments. Asking the same question several times or repeating stories is very common. While this sign is seen often in dementia, it is also a typical sign of aging as well as mild cognitive impairment, which can be, but is not always, an early warning indicator of Alzheimer’s disease. Memory loss may also be a sign of depression; B12 deficiency; kidney, brain, thyroid, or liver disorders; or a side effect of certain medications.
Challenges in planning or solving problems
An occasional mix-up while balancing a checkbook can be a common sign of aging. Losing track of monthly bills can be a more serious sign. An inability to concentrate or difficulty following a familiar recipe may warrant a doctor’s visit. Planning may become almost impossible for those in the earliest stages of dementia and indicates a deficit in executive functioning. Difficulties with problem-solving can also signal other health issues ranging from serious conditions like a brain tumor to less insidious conditions such as stress.
Difficulty completing familiar tasks at home, at work, or at leisure
Often in early dementia, the simplest tasks become increasingly difficult. While older people may have trouble with operating a computer or the settings on a television remote—and this can be a normal symptom of aging—those with dementia can’t perform daily tasks that were once a part of their routine. Getting dressed can become a major undertaking. The real difficulty actually comes with the sequence or order of doing things. Writing out the steps to tasks such as preparing a meal and leaving them in easily accessible places can be helpful.
Confusion with time or place
Often people in the early stages of dementia forget the time and even lose track of months and seasons. While many retired people may forget what day it is because they no longer go to work and live by a calendar, the sort of confusion surrounding time is much more severe in those with dementia. Losing track of where they are or how they got to certain places is common and should be investigated by a doctor. This type of confusion may be acute and occur suddenly or may happen over time. Those afflicted will often experience periods of confusion surrounding time and place and then revert to their old selves. Perception of time and time distortion are also issues for those struggling with dementia. They may believe they haven’t seen a loved one for months or years, when in fact it was only days ago.
Trouble understanding visual images and spatial relations
Difficulty understanding visual images and spatial relations can impact depth perception, which can cause an increased risk of falling and can make feeding and bathing more challenging. Driving difficulty due to problems with spatial relations is quite common, and navigating turns and changing lanes can become dangerous. Often people with dementia are forced to give up driving. Reading also becomes a problem, not only because of the visuospatial issues, but also due to an inability to understand words. A 2016 study of visuospatial skills in dementia patients found that those with certain types of dementia, including Alzheimer’s disease, dementia of Lewy bodies, and vascular dementia, performed poorly in comparison to controls when examining space and object perception. The study found that significant impairment of visuospatial functions occurs in the early stages of dementia and worsens as the disease progresses.
New problems with words in speaking or writing
While aging can cause an occasional problem with finding the right word, communication issues are much more significant in the early stages of dementia. Following conversations and finding the correct words for objects is difficult for those with dementia, and this early warning sign should be brought to a doctor’s attention. Aphasia, a type of language disorder, impacts communication including speech, writing, and language comprehension. According to the Mayo Clinic, “Primary progressive aphasia is a type of frontotemporal dementia.” Of course, there are other medical conditions that can cause language and communication issues including strokes, brain tumors, and brain injuries.
Misplacing things and losing the ability to retrace steps
Misplacing things could mean putting objects in strange places, like placing car keys in the microwave, and it is a common sign of dementia. Those struggling may also have difficulty in retracing their steps to find the things they’ve lost. This lack of ability to retrace steps differentiates this as a sign of dementia versus a normal sign of aging. It can be both dangerous and frustrating. As the disease progresses, the afflicted person may accuse others of stealing things that have been misplaced.
Decreased or poor judgment
During the early stages of dementia, decision-making is impacted and can cause poor judgment. People may spend money foolishly or have a hard time remembering to feed and walk a pet. They may also pay less attention to grooming and personal hygiene. Those struggling with dementia are especially susceptible to scams involving money. One poor decision should not be considered an indicator of dementia though. Instead, look for a pattern which might include things like constantly wearing summer dresses even though it’s winter, or walking in a busy area and not paying attention to traffic lights.
Withdrawal from work or social activities
Not wanting to participate in social activities once enjoyed, like golf or going to church, may be a sign of dementia. Because of an inability to follow conversations or participate in hobbies and comprehend them in a familiar way, things like watching a favorite sport or going to family dinners might become less enjoyable. This may cause people with dementia to withdraw. They may sleep more frequently or spend more time sitting in front of the television. Social withdrawal could also be a symptom of depression, anxiety, or post-traumatic stress disorder.
Changes in mood and personality
While being sad or experiencing a shift in mood can happen to almost anyone occasionally, mood and personality changes may be early indicators of serious health issues. These can include mental health conditions, hormonal changes, or substance abuse problems. When those with dementia experience these symptoms, they can manifest as fear, suspicion, and getting easily upset or becoming irritable over minor things. Things that never would have bothered them before often will now. They may also lose patience more quickly. The National Institute on Aging recommends doing several things to help navigate these changes in mood and personality, including having a daily routine and using humor when appropriate.
This story originally appeared on Neural Effects and was produced and distributed in partnership with Stacker Studio.
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