The condition we now know as Alzheimer’s disease (AD) has likely been a part of the human experience for centuries, but it first received a clinical name in 1906 when a German psychiatrist and neuroanatomist, Dr. Alois Alzheimer, reported the case of a 50-year-old woman with progressive cognitive decline and memory loss until her death five years later. His analysis of her brain tissue revealed numerous distinct plaques and neurofibrillary tangles. Despite Dr. Alzheimer’s findings, the scientific community was slow to acknowledge the condition.
Fast forward to 2020 and the story is very different. With 5.8 million Americans living with Alzheimer’s disease in 2019, odds are you know someone who has been touched by the disease. And again, odds are that that someone is over the age of 65. The Alzheimer’s Association reports that of those 5.8 million with AD, 5.6 million are ages 65 or older with as few as 200,000 under the age of 65. Unfortunately, these numbers are only expected to rise as the American population ages. Between 2019 and 2025, the number of people living with AD in the U.S. is expected to increase by 12 percent annually, which is why the push to find a cure for AD is so strong.
To understand how AD affects the brain, it is important to understand on the most basic level how our brain works. The brain is comprised of more than 100 billion cells called neurons, each of which has long extensions that allow one neuron to communicate with other neurons. Where these extensions interface is called a synapse, and it is here that a multitude of chemicals, each of which plays a different role in brain function, are released, allowing neurons to communicate and, ultimately, allowing us to do everything from talking to remembering.
In AD these functions are compromised by two hallmark features:
- Plaques are formed by sticky clusters of a protein called beta-amyloid, which accumulate outside of neurons where they are thought to interfere with communication between nerve cells at the synapse.
- Tangles are formed from abnormal accumulations of another protein called tau that develop inside neurons as part of the AD process. Researchers believe that tangles disrupt the transport of critical nutrients and other substances within the neuron.
Both features impact normal brain cell activity, eventually leading to cell death and thus atrophy or shrinkage of the brain. And during this process, memory gradually deteriorates, affecting a person’s judgment and ability to perform normal daily activities.
Stages of Alzheimer’s
The typical Alzheimer’s case progresses gradually, with steady deterioration over as many as 20 years, although some people have a more rapid course. This progression has been categorized into stages for diagnostic purposes, although an individual with AD may have some overlap of features common to the various stages.
Although every patient is different, there are general trends for timing of symptom onset and order of symptoms experienced for people with AD. People suffering from late-onset AD, the most common form of AD, typically begin experiencing noticeable symptoms in their mid-60s. By contrast, those suffering from the less common early-onset AD may begin to display symptoms as early as the mid 30s. Among the earliest symptoms experienced are deficits in memory. Early non-memory cognitive deficits include impairments in judgement or reasoning, word-finding, and visual or spatial orientation. Predictably, as the disease progresses, these symptoms worsen, though the rate of disease progression can depend on age at diagnosis and other health conditions.
Preclinical Alzheimer’s
With advances in research comes the knowledge that toxic changes are occurring in the brain of individuals destined to develop AD long before cognitive or memory symptoms occur. Damage may start 10 or more years before there is any overt sign that someone has AD. Scientists are calling this “preclinical Alzheimer’s disease” and, while this stage is rarely diagnosed outside of the research setting, the hope is that one day effective therapies can be used to target those early changes before symptoms develop.
Mild Cognitive Impairment (MCI)
It can be a bit misleading to place MCI between preclinical AD and early stage/mild AD, because not all MCI progresses to AD. In a large meta-analysis of multiple studies, researchers found that among patients diagnosed with MCI who were followed for five years or longer, 38 percent went on to develop AD. Research shows that people with MCI involving memory deficits—also called amnestic MCI—are, in particular, more likely to develop AD.
MCI is sometimes described as one step beyond normal age-related memory loss but one step before AD. Someone with MCI has a lot of trouble remembering simple things—for example, a familiar telephone number or where he or she put the car keys.
The person will have more trouble remembering names or words, acquiring and retaining other information, and performing complex tasks. These cognitive lapses may become increasingly noticeable to others; however, one key feature of MCI is that overall daily functioning remains intact.
Early-Stage (Mild) Alzheimer’s
Someone with mild Alzheimer’s can still be independent but may notice progressive difficulty in performing multi-step tasks, such as following a recipe to prepare a meal or setting up a filing system for household bills.
Family and friends might observe signs like forgetting familiar words, trouble recalling current events, or remembering dates. The person can have trouble following conversations (particularly in groups), become increasingly withdrawn in social situations, and be less interested in going out or engaging in other activities.
Depression and anxiety also are common, and these emotional changes can put a strain on relationships with family and friends. This often is the stage where someone affected will have to stop working if they are still employed.
Mid-Stage (Moderate) Alzheimer’s
This is the longest stage of AD and the one in which life begins to become most impacted by disease. It is also the time when living alone becomes impractical, even with help from family and friends.
The person will be unable to remember important information, such as his or her address or phone number. He or she likely will need help picking out clothes and remembering the date and time of day.
Behavior changes become much more pronounced in this stage: increasing irritability, anger, anxiety, and depression are common. The person may become confused or delusional at times and express irrational fears—for example, that someone is stealing from him or her, often an explanation for items that are lost. Changes in sleep patterns may occur, with increasing daytime sleepiness and nighttime restlessness.
Late-Stage (Severe) Alzheimer’s
Cognitive ability becomes seriously compromised at this stage, as the person becomes unable to communicate or interact with his or her environment and loses the ability to recognize family and friends. He or she will need help performing even the simplest tasks, such as using the bathroom or eating. Most individuals also experience trouble with bowel and bladder control.
Although medications may help moderate symptoms, the disease is still incurable and irreversible. However, treatments and support systems can significantly improve quality of life for people with AD and their families.
Alzheimer’s Pathology
Although scientists have yet to identify one definitive cause for AD, every year brings them closer to understanding all the factors that influence disease development. Those factors include age, which is the most significant risk factor in the development of AD. 
Rare genetic mutations also come into play in a small percentage of people with the disease.
What remains elusive is how these factors set the disease process in motion. Understanding this process could help them develop diagnostic tests to determine who is at high risk for AD so they can treat people earlier, before symptoms appear.
Amyloid Hypothesis
In its original iteration, the term “amyloid hypothesis” was used to describe the idea that beta-amyloid was responsible for Alzheimer’s disease. While most experts now agree that AD is more likely a multifactorial process, the term is still sometimes used to describe what has been the mainstream school of thought on disease causation for the past 25 years. Beta-amyloid is a small piece of a larger protein called amyloid precursor protein (APP) that extends from the inside to the outside of a nerve cell, through the cell membrane. When activated, APP is cut by enzymes into smaller fragments that accumulate within and around the nerve cell. One of these fragments, beta-amyloid, accumulates outside of the cell and in a healthy brain, is then removed. While scientists don’t know precisely what the normal function of beta-amyloid is, they do know that, in AD, the brain does not appear to remove beta-amyloid. Instead, this protein accumulates and forms sticky masses, or plaques. These plaques destroy neurons, trigger the development of tau protein, and cause the gradual loss of brain tissue (see “Amyloid Hypothesis: Plaques and Tangles”).
The biggest boost for the amyloid hypothesis came from the discovery in the 1990s that dominant inherited mutations in genes encoding the enzymes that cut APP were responsible for the familial forms of AD. These mutations result in APP being preferentially cut into longer forms of beta-amyloid that are more prone to clumping than normal beta-amyloid. Then, in 2014, Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research unit, and his team made a significant breakthrough that further supports the amyloid hypothesis. Their research provided the first concrete evidence that the deposit of beta-amyloid plaques in the brain can launch the process of neurological damage including tangle formation and ultimately cell death. (See “Healthy Neuron vs. Neuron with AD.).
In the past, beta-amyloid was viewed as essentially useless junk that does nothing more than damage the brain. Yet Dr. Tanzi and his colleagues recently introduced a theory that could upend our current understanding of the disease. They suggest that, rather than being useless, beta-amyloid is an antimicrobial protein unleashed by the immune system in response to infection in the body.
In a May 2016 study published in Science Translational Medicine, Dr. Tanzi and his team found that beta-amyloid protected against bacterial and fungal infections in mice and worms, and that mice infected with salmonella bacteria developed the plaques common to AD. They theorized that infection can set off beta-amyloid development, which leads to tau deposits and the inflammation that damages brain cells.
More recent research by Dr. Tanzi and others has lent further support to this theory. In a study published in 2018 in the journal Neuron, Dr. Tanzi and colleagues showed that in mice models and human neural cell cultures, exposure to herpes viruses stimulated rapid buildup of beta-amyloid. The beta-amyloid binds to the viral particles and quickly begins to fibrilize, essentially trapping the viral particles in a sticky net of amyloid fibrils and destroying them within hours. The study authors concluded that “in the early history of humans, early onset familial Alzheimer’s mutations may have conferred a selective advantage against childhood or early adult brain infections.”
Despite the lack of consensus on beta-amyloid’s intended function, the current iteration of the beta-amyloid hypothesis is that beta-amyloid is the driving force behind the disease, triggering a cascade of damaging events in the brain. Dr. Tanzi uses the analogy of a forest fire, likening beta-amyloid to a match that starts a bush fire of tau tangles that subsequently ignites a forest fire of inflammation in the brain.
As a result, he says, trying to target beta-amyloid in patients with full-blown dementia is like trying to put out a forest fire by blowing out the match. This theory is often cited by 
experts who attribute the many recent failures of a host of different drugs targeted toward beta-amyloid to the fact that they are being administered too late in the course of the disease to reverse damage. This has shifted the focus of beta-amyloid targeting research too early in the course of the disease—before the beta-amyloid can trigger the chain of events that lead to full-blown dementia.
One such focus is on the immune cells of the brain, called microglia. Microglia can be activated to exist in an inflammatory state in which they release inflammatory proteins that damage neurons or in a phagocytic state in which they clear away debris like beta-amyloid and tau tangles. New research is targeting the genes that turn the inflammatory state on (CD33) and off (TREM22) with the hope that if you can prevent the inflammatory state and promote the phagocytic state, you could target beta-amyloid, tau, and inflammation—the three major factors involved in disease progression.
Tau Hypothesis
The amyloid hypothesis has been the focus of drug development for AD. The idea has been that drugs aimed at reducing production, preventing aggregation, or enhancing removal of beta-amyloid might be the key to preventing, slowing, or even reversing dementia. Yet after multiple studies of beta-amyloid-targeting drugs failed, researchers began calling the amyloid theory into question. Although investigators are still actively following the amyloid line of research, they also continue to look at other possible avenues of origin—including tau, the other major player in Alzheimer’s development.
The tau hypothesis centers on an abnormal form of tau protein that forms twisted fibers called neurofibrillary tangles that accumulate inside brain cells of people with Alzheimer’s. Normally, tau 
protein builds part of a cellular structure called a microtubule, which helps transport nutrients and other substances from one part of the nerve cell to another. When tangles form, the microtubules break down, leading to the deterioration of connections to other cells and, eventually, to cell death (see “Tau Hypothesis: Twisted Neurofibrillary Fibers”).
When researchers at the Mayo Clinic in Florida tracked the evolution of both amyloid and tau in brain tissue, they found the amount of tau, not amyloid, predicted the age at which people developed the disease and their degree of cognitive loss. They say this finding suggests tau is the driver of Alzheimer’s. Other research has demonstrated that abnormal tau lesions occurred earlier than beta-amyloid accumulation in some people with AD.
Though the beta-amyloid vs. tau origination theories are still being debated, researchers at Massachusetts General Hospital have discovered how neurofibrillary tangles spread throughout the brain. Using a mouse model of the disease, they identified a rare version of the tau protein with a high molecular weight and structure that enables it to pass easily from one neuron to the next. When this protein is released from one neuron, it is taken up by another neuron, moving up the neuron’s axon to be released to yet another neuron.
“Our findings suggest that the release and uptake of this form of tau is an important step in the spread of disease from one brain region to another,” says Bradley Hyman, MD, PhD, director of the Massachusetts Alzheimer’s Disease Research Center at MGH. “Since that spread likely underlies clinical progression of symptoms, targeting the mechanisms of the spreading might hold promise to stabilize disease.”
Even before tau tangles form, this protein already has begun to disrupt communication among nerve cells, according to researchers in Belgium. Normally, tau proteins are connected to the cell’s cytoskeleton—the area where the microtubules are housed. In the nerve cells of people with AD, tau comes loose from the cytoskeleton and forms the abnormal tangles. The researchers discovered that once tau is dislodged, it settles on synapses—the connections between nerve cells across which impulses travel—and interferes with message transmission. They say methods to prevent this communication interruption might also halt the death of nerve cells that follows.
Because of the early focus on beta-amyloid, anti-tau research has generally lagged behind beta-amyloid research. That is beginning to change, however, as more anti-tau studies start to populate the research pipeline. While most of these are early studies, researchers hold hope that they will offer promise as more and more experts begin to agree that tau plays a key role in disease progression.
Oligomers
In recent years smaller, non-plaque, non-tangle forms of beta-amyloid and tau called oligomers have gained attention as potential culprits in AD pathology. Beta-amyloid oligomers are variants of the protein that exist outside of plaques. They’re thought to disrupt communication in the brain by changing the structure of communication points between brain cells known as synapses, and by promoting the development of tau tangles. Many scientists now believe that beta-amyloid oligomers are more toxic to neurons than plaques. A 2013 study demonstrated the concentration of beta-amyloid oligomers surrounding plaques served as a distinguishing factor in the brains of individuals with dementia from those without but who had a similar beta-amyloid plaque burden.
Recently, a drug that targets amyloid oligomer, BAN2401, has shown promise in slowing cognitive decline and reducing amyloid accumulation. In a phase 2 study, cognitive decline was slowed by 47 percent on the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) test and 30 percent on the AD Composite Score (ADCOMS) test in individuals with early AD who took the highest dose of the drug. This dose of the drug also reduced beta-amyloid by up to 93 percent. A phase 3 trial of the drug began in March 2019 and is expected to run through 2024.
Tau oligomers are an intermediate form of tau protein that occurs during the neurofibrillary tangle development process. Increasingly, evidence suggests that tau oligomers—rather than tau tangles—might be the real mediators of neuronal damage. Because tau oligomers appear earlier in the disease, causing neuronal dysfunction before tangles even appear, they could provide a new therapeutic target for AD.
When researchers at the University of Texas used immunotherapy to target tau oligomers in an animal model of AD, the treatment both reduced levels of tau oligomers and reversed memory declines. Immunotherapy also reduced levels of beta-amyloid oligomers, suggesting the two types of oligomers work in concert to damage the brain. The therapeutic potential of oligomers is limited at the present time, because scientists cannot yet measure them in living people. However, researchers are hopeful that anti-oligomer therapies might be a promising treatment area in the future.
Cholinergic Hypothesis
The cholinergic hypothesis was introduced more than 30 years ago, and it’s the foundation for one of the main AD drug treatments. The hypothesis suggests that AD symptoms result from a decrease in production of the neurotransmitter acetylcholine, which is necessary for learning and memory formation. Its production is known to decline with age, but AD is associated with a much more significant decline in acetylcholine levels.
The cholinesterase inhibitor drugs that are a mainstay of AD treatment work by blocking the action of an enzyme that normally breaks down excess acetylcholine for removal, thus increasing acetylcholine levels in the brain. But while cholinesterase inhibitors can slightly improve memory and the ability to carry out daily activities, they can’t slow AD progression. Today, the cholinergic hypothesis has been largely abandoned as the root of AD development. It is more commonly thought that cholinergic impairment represents one part of the multifactorial progression of AD.
An important side note, however, is that anticholinergic drugs targeting different sites in the body are a commonly prescribed class of drug. Over the years, studies have shown an association between anticholinergics and cognitive impairment, particularly with long-term use (see “Anticholinergics: Dementia Impact Is Drug-Specific”).
A British study published in 2018, however, identified that the risk appears to be drug-specific. Using a database of almost 41,000 patients diagnosed with dementia between 2006 and 2015, they looked at their anticholinergic drug-taking history for as long as 20 years prior to diagnosis and compared that with a large control group of patients without dementia.
They found that the anticholinergics procyclidine (Kemadrin), used to treat Parkinson’s disease, and oxybutynin (Ditropan), used to treat urinary incontinence, were associated with a significantly increased risk—up to 30 percent—of dementia, even when they were taken 20 years earlier. By contrast, anticholinergics used to treat gastrointestinal, respiratory, and cardiovascular disorders were not associated with an increased risk of dementia.
The study authors cautioned that careful consideration of these findings should be given when prescribing these anticholinergics—a fact that has wide-reaching implications given that as many as 15 percent of men and 50 percent of women in the United States suffer from urinary incontinence.
Inflammation
Although much of the focus on AD development has been on tau and beta-amyloid, chronic inflammation is also a core feature of the disease. The immune system relies on inflammation to combat
viruses, cancers, and other dangerous invaders. But when inflammation persists, it can damage cells—including neurons. AD has been linked to head injury, which causes inflammation in the brain, as well as to infection, which can lead to body-wide inflammation. As mentioned earlier, a growing field in AD research has been the focus on infection as a potential trigger for beta-amyloid aggregation.
Having surgery also might set off the inflammatory process. Doctors have long been aware that their older patients sometimes experience cognitive decline after surgery, although whether this results from inflammation or anesthesia, or is simply unmasking previously existing cognitive impairment, remains unclear.
Excitotoxicity
In the theory of excitotoxicity, over-activation of receptors for the neurotransmitter glutamate is to blame for AD nerve damage. Glutamate is normally responsible for making neurons “fire” as they relay messages through neuronal networks. It helps establish long-term memories. When normal glutamate processes are disturbed, excessive amounts of this chemical messenger build up in the space between brain cells. The excess glutamate attaches to brain cells, overstimulates them, and ultimately leads to cell death. The AD drug memantine (Namenda) works by blocking the effects of excess glutamate, but although memantine can improve symptoms of moderate-to-severe AD, it does not stop cognitive decline.
Excitotoxicity has been linked to AD, stroke, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). However, in AD, it is likely not a triggering factor.
Oxidative Stress
Oxidative stress occurs when unstable molecules called free radicals, generated by factors such as environmental toxins and stress, overwhelm the body’s natural antioxidant defense system. As a result, the body falls behind in its repair of cellular damage. The brain is particularly vulnerable to oxidative stress due to its cellular composition. Oxidative stress is a normal part of the brain aging process, but in AD it seems to play a bigger role. Not only does oxidative stress appear to be more pronounced in AD, but the brain also appears to have less antioxidant capacity.
Research suggests high levels of free radicals and oxidative stress are among the earliest changes that occur in AD and may play a role in mediating the damage from abnormal beta-amyloid and tau proteins. But oxidative stress is a marker, not a cause. Despite the strong evidence that oxidative stress is a part of AD pathology, clinical trials using antioxidant therapy for AD have either yielded inconclusive results or have failed.
Chemicals we use every day might hasten this damaging oxidative process—including pesticides. These chemicals kill insects by attacking their nervous system, and it’s theorized they also can be harmful to the human nervous system. Repeated pesticide exposure, even at small doses, could cause problems with oxidative stress, cell dysfunction, and loss of nerve cells, which might contribute to neurodegenerative diseases such as AD. One category of pesticides has been linked to AD—organophosphates, found in herbicides and solvents. However, most neurodegenerative diseases are multifactorial, triggered by a combination of environmental and genetic factors.
Leaks in the Blood-Brain Barrier
The brain is a critical and delicate organ. If dangerous substances were to easily pass through the blood vessels into the brain, the results could be disastrous. For this reason, the brain has a built-in blockade that restricts access to any dangerous foreign materials that enter the bloodstream. It’s called the blood-brain barrier. Throughout the rest of the body, blood vessels are lined with endothelial cells, which have spaces in between to allow substances to move in and out of the vessels. Yet in the brain, endothelial cells are densely packed. While essential substances like water and glucose can pass into the brain, potentially harmful substances are barred from entering.
Researchers using contrast-enhanced MRI have discovered that Alzheimer’s patients have much larger leaks in the blood-brain barrier than healthy adults of the same age, and that the more leakage people have into their gray matter (the tissue where neurons are concentrated), the worse they score on tests of cognitive function. However, the implications of this finding are still unclear.
At the 2018 Keystone Advances in Neurodegenerative Disease Research and Therapy Symposia, scientists from the Mayo Clinic presented research showing that apolipoprotein E4 (ApoE4)—a gene associated with an increased risk of AD—expressed in other areas of the body (apolipoprotein cannot cross the blood-brain barrier) may impact the integrity of the blood-brain barrier.
The researchers engineered mice whose ApoE expression was limited to the liver and nowhere else, including the brain.They then noted that not only did the mice with ApoE4 perform worse on cognitive tests than mice with other ApoE variants, but the ApoE4 mice also had leakier blood-brain barriers and slower blood flow through the small blood vessels of the brain than mice with other variants of the ApoE allele. Though there is still much to learn, evidence suggests the brain can lose the protective mechanism that shields it against damage.
Insulin Abnormalities
Insulin is a hormone most closely associated with diabetes. Normally, insulin moves sugar from the bloodstream into the cells to be used for energy or stored. In people with diabetes, the body either doesn’t produce insulin, or can’t use it effectively, leading to a buildup of sugar in the bloodstream and resulting in damage to organs such as the kidneys and eyes.
More recently, evidence has linked insulin irregularities in the brain to AD (see “High Blood Glucose and Cognitive Decline”). Researchers discovered that insulin has many important functions in 
the brain. In the early stages of AD, insulin levels drop significantly and progressively decline as the disease advances. Cell death and neurofibrillary tangles appear to be linked to abnormalities in insulin signaling. The theory has led to suggestions that AD may be a type of diabetes with some going so far as to call it “type 3 diabetes.” Now, researchers are investigating whether giving insulin to people with early cognitive impairment might slow this decline.
While the precise mechanism for how insulin abnormalities are related to AD remains unknown, the evidence for an association is mounting. A recent British study published in the journal Diabetologia showed that elevated blood glucose levels—even those that don’t qualify as diabetic—were associated with faster rates of cognitive decline.
The researchers used data collected between 2005 and 2015 for 5,189 individuals age 50 and older. They monitored hemoglobin A1C (HbA1C)—a reliable blood marker that reflects average blood glucose levels over a two to three-month period—diabetes status, and cognitive performance over the 10-year period.
After controlling for baseline age, sex, cholesterol levels, C-reactive protein (a marker for inflammation), body mass index, education, marital status, smoking, alcohol consumption, hypertension, heart disease and stroke, lung disease, cancer, and depression, they found a significant association between rate of cognitive decline and A1C levels. Those individuals whose A1C levels were consistent with prediabetes or diabetes had significantly faster rates of cognitive decline, including in global cognition, memory, and executive functioning than those individuals whose A1C was normal.
The researchers say their “findings suggest that interventions that delay diabetes onset, as well as management strategies for glucose control, might help to alleviate the progression of subsequent cognitive decline over the long term.”
Trials conducted so far on a nasal spray that delivers insulin directly to the brain have resulted in improvements to both cognition and memory. Insulin may help slow or even halt the progression of neurodegeneration in people with MCI or AD (see Chapter 7). Further studies are needed to confirm the effectiveness and safety of insulin therapy in people with MCI and AD.
The Gender Link
Dementia caused by AD and other pathologies affects more women than men. Two-thirds of Americans suffering from AD are women. Exactly why is not fully understood. For years, the theory was that women live longer than men and, because age is the leading risk factor for AD, women were naturally going to make up the larger contingency. However, recent research suggests that the association is more nuanced.
Historically, it was thought that women progressed to cognitive loss almost twice as quickly as men, but research presented at the 2018 Alzheimer’s Association International Conference indicated that women’s advantage in verbal memory may make it harder to identify early stages of AD and thus delay their diagnosis. After examining data from the Alzheimer’s Disease Neuroimaging Initiative, researchers from the University of Illinois, Chicago and the University of California San Diego found that women performed better than men on a variety of verbal recall tests despite having similar levels of mild-to-moderate Alzheimer’s pathology as measured by parameters such as brain atrophy and beta-amyloid deposition. This performance discrepancy was eliminated when the disease pathology was more advanced. The researchers conclude that these findings suggest there may be a need for gender-specific cognitive assessment scoring to enhance early diagnosis in women.
Other research suggests that the ApoE4 genotype, the most well-known genetic risk factor for AD, may have a stronger association with dementia in women than in men and a stronger correlation with AD biomarkers in women than in men. Although this hasn’t been borne out in all studies, there is some evidence that sex hormones, particularly as they relate to reproductive history, may play a role in this relationship.
In research presented at the 2018 Alzheimer’s Association International Conference, scientists from Kaiser Permanente and the University of California Davis looked at reproductive health of almost 15,000 women between the ages of 40 and 55. The researchers compared these histories with subsequent development of dementia and found that:
- Women who had their first menstrual period at age 16 or older had a 31 percent greater risk of dementia than women who reported having had their first menstrual period at age 13 (the average reported age in the study).
- Women with three or more children had a 12 percent lower risk of dementia compared with women who had only one child, even after adjusting for other dementia risk factors, including BMI and stroke history.
- Miscarriage conferred a 9 percent increased risk of dementia with each event compared with no miscarriages.
- Menopause at or before the age of 45 was associated with a 28 percent higher risk of dementia compared with menopause after age 45.
- A reproductive period (time between first menstrual period and menopause) of 21 to 30 years was associated with a 33 percent increased risk of dementia than a reproductive period of 38 to 44 years.
In another study, researchers from the University of California Los Angeles reported that in a study population of 133 British women, those who spent 12.5 percent more months pregnant than women who had similar risk profiles had a 20 percent lower risk of AD.
Most recently, researchers from Vanderbilt University presented evidence at the 2019 Alzheimer’s Association International Conference that tau appears to spread more easily throughout the brains of women than men, potentially accelerating the rate at which it accumulates in women and putting them at greater risk of cognitive decline.
Risk Factors for Alzheimer’s
In its 2019 Alzheimer’s Disease Facts and Figures Report, the Alzheimer’s Association reports that the lifetime risk of developing AD at age 45 is roughly 20 percent for women and 10 percent for men. The risks jump slightly to 21 percent and 12 percent, respectively, at age 65.
Risk factors for Alzheimer’s disease are often divided into two categories: those that are unmodifiable and those that are modifiable. The unmodifiable risk factors, unfortunately, are also the greatest risk factors: age, carrying the e4 form of the APOE gene, and family history. Nonetheless, there is a host of modifiable risk factors that, if addressed or changed, can potentially reduce your risk of developing dementia.
In their 2017 report, the Lancet Commission on dementia revealed that 35 percent of all dementia cases could be prevented if nine modifiable risk factors were addressed:
- Early Life Factors (age <18):
- Poor early school education
- Midlife Factors (age 45-65):
- Hearing loss
- Hypertension
- Obesity
- Late Life Factors (age >65):
- Smoking
- Depression
- Physical inactivity
- Social isolation
- Diabetes
By comparison, if one unmodifiable risk factor—the gene ApoE4—were eliminated, only 7 percent of Alzheimer’s cases could be prevented. Because many of these conditions are lifestyle-related, you can make a few changes to help reduce your chance of developing dementia.
Unmodifiable Risk Factors
Age. The single biggest risk for AD is increasing age. After you reach age 65, your risk doubles about every five years. By age 85, nearly one-third of all people have Alzheimer’s. However, Alzheimer’s is not an inevitable part of aging, and it’s important to understand why some individuals get the disease in their 60s and others remain intact into their 80s and beyond.
Genetics/Family History. Genes—those tiny units of heredity that carry characteristics like eye color and height from parents to their children—also play a role in whether those children will eventually develop AD. The more family members you have who are affected by Alzheimer’s, the greater your risk becomes.
As of 2009, researchers had discovered only four gene mutations related to AD. The first three involve mutations in the genes for APP, presenilin 1 and presenilin 2 proteins. Each of these mutations influences the breakdown of APP, a process that, though not fully understood, appears to play a role in the formation of amyloid plaques. Mutations in these genes account for 1 percent or less of all Alzheimer’s cases and almost invariably result in disease that begins before age 65 and as young as 30. Inheriting the mutation to the APP or presenelin 1 gene always results in AD, while there is a 95 percent chance of disease when the presenilin 2 gene is inherited.
While these mutations are associated with a dire prognosis, our ability to learn from these genetic mutations is constantly growing. For example, a recent study by researchers at Massachusetts General Hospital demonstrated that in individuals with the inherited genetic mutation in presenelin 1, tau deposits were visible on PET scan roughly five years before onset of clinical symptoms. Additionally, levels of tau deposition seen on PET scan correlated closely with cognitive decline (higher levels = faster rate of decline), suggesting that tau PET scans might be able to identify AD in a shorter, potentially more actionable time window before the start of clinical disease.
The fourth genetic component identified was a variant of the ApoE gene. ApoE is a gene for a protein that helps transport cholesterol through the bloodstream and remove it from the body. We all inherit one form of the ApoE gene from each of our parents, but the specific variants we inherit can impact our susceptibility for the late-onset form of the disease. There are three known variants, ApoE2, ApoE3, and ApoE4.
ApoE2 appears to confer a protective effect against AD, while ApoE3 has a neutral effect, providing neither protection nor increased risk. ApoE4 is associated with an increased risk, with one copy carrying a threefold increase and two copies carrying an eight- to 12-fold risk. Population-based studies have shown that about 25 percent of the population has at least one copy of the variation ApoE4, while only 2 percent carry both copies of the ApoE4 variant. More recent research has indicated that women with ApoE4 seem to be more likely than men to develop active AD, possibly through a higher production of tau protein.
“It is not yet clear precisely how ApoE4 affects the brain,” says Deborah Blacker, MD, ScD, director of the Gerontology Research Unit at Massachusetts General Hospital. “But they are clearly at increased risk of developing Alzheimer’s.” However, many individuals with two copies never get the disease, and many Alzheimer’s patients do not carry the ApoE4 variant. As a result, testing for it is not currently considered a useful predictive tool, though it has been used to select individuals for therapeutic trials, currently underway, based on higher risk.
The mechanism of action of ApoE in leading to AD is unknown. It may help break down sticky clusters of beta-amyloid protein that can clog the spaces between brain cells. In people with the genetic variation ApoE4, the ability to degrade beta-amyloid is impaired,and studies have associated the ApoE4 variant with an increased number of beta-amyloid plaques in the brain.
Other Genes Identified. Since 2009, there has been an explosion in research identifying new genetic factors that may play a role in the development of AD, some of which focus on cellular 
functions that occur at early, pre-diagnosis stages. Inherited variants of the sortilin-related receptor 1 (SORL1) gene may be involved in the abnormal production of beta-amyloid plaque in the brains of people with late-onset AD by determining whether APP is recycled within the cell or shunted toward beta-amyloid production.
A variant of the cell division cycle 2 gene (CDC2) has been associated with increased production of tau protein. And changes to the gene that codes for brain-derived neurotrophic factor (BDNF)—a protein that protects nerve cells—are linked to faster memory declines in people at risk for Alzheimer’s. Gene therapy studies in animals in which the normal BDNF gene is delivered to animals with the abnormal form have shown promising results in achieving restoration of neurologic symptoms.
A breakthrough international study released a few years ago yielded 11 new “susceptibility loci” (location of the genes on a chromosome) for Alzheimer’s—a number which has since increased to 24 and counting. Researchers highlighted several previously noted pathways, including those related to amyloid and tau. But they also identified several new pathways, including ones related to inflammation, the immune response, and lipid transport. These susceptibility loci might eventually lead to new diagnostic techniques or treatments for Alzheimer’s.
In 2017, researchers from the United Kingdom announced they had discovered two new genes associated with late-onset Alzheimer’s, called PLCG2 and ABI3. The massive hunt to find these genes involved sifting through DNA from more than 85,000 people with and without AD. The researchers say the two genes are related to cells called microglia, which clean up damaged proteins and other debris in the brain. The finding could potentially lead to new Alzheimer’s drug targets.
Thanks to recent advances in our understanding of Alzheimer’s susceptibility genes, researchers at Massachusetts General Hospital have developed a genetic risk score for AD. They calculated this score, which they called polygenic risk score (PGRS), based on the presence of certain Alzheimer’s gene variants. Though it’s still in the early stages, this test, or one like it, might one day identify people at high risk for the disease, long before their symptoms appear.
Recently, a team of scientists from The Netherlands published their research on another genetic predictive score—called the genetic risk score, or GRS—in The Lancet Neurology. The scoring system, which is designed to predict cumulative risk and age at AD onset, was developed after following approximately 15,000 individuals for 11 years and assessing the 24 known genetic variants associated with AD.
It should be noted that, except for ApoE4, none of these genes individually has a meaningful effect of Alzheimer’s disease risk. However, taken together, they may be used to assess risk and potentially target individuals for prevention strategies.
Modifiable Risk Factors
Hearing Loss. Over the past decade, a growing body of evidence has demonstrated that hearing loss is associated with a risk for cognitive decline. In 2011, researchers from the Johns Hopkins School of Medicine reported that hearing loss was significantly associated with all-cause dementia after following 639 individuals for approximately 12 years who were cognitively normal at the beginning of the study.
In a larger study of 2,000 cognitively normal older adults (average age 77), the same researchers found that those individuals who started the study with hearing loss significant enough to interfere with conversation were 24 percent more likely to develop cognitive impairment than those with normal hearing over the course of six years. A study published in 2019 in JAMA Open Network looked at over 16,000 Taiwanese citizens and found that hearing loss was significantly associated with a risk of dementia, particularly among people between the ages of 45 and 64 years old.
So, as hearing loss can’t be prevented, how do you modify this risk factor? A seminal study published in JAMA Otolaryngology-Head & Neck Surgery by French scientists looked at 94 people ages 65 to 85 with profound hearing loss in at least one ear. Each patient received a cochlear implant along with twice-weekly auditory rehabilitation and underwent cognitive testing. The researchers found that more than 80 percent of those individuals with the lowest initial cognitive scores had significant improvement a year after receiving the implant. Additionally, rates of depression among the patients dropped significantly. At the 2019 Alzheimer’s Association International Conference, researchers from the University of Exeter presented data from a two-year online study of over 25,000 individuals. They found that those who wore hearing aids performed better on cognitive tests—particularly in the areas of working memory and attention—than those who did not have hearing aids.
While most experts agree that larger studies need to be carried out to definitively establish the impact hearing aids might have on dementia risk, they also point to the fact that there are few downsides to both protecting and improving your hearing, and you may just be helping your brain in doing so. Without more studies, it remains unclear how hearing loss negatively affects the brain.
High Blood Pressure and Stroke. High blood pressure is one of the most common conditions affecting adults, and the number of people affected just got bigger. In 2017, the American Heart 
Association lowered the blood pressure measurement it uses to define hypertension from 140/90 to 130/80. That raised the number of people living with high blood pressure in the United States to over 100 million, roughly 46 percent of all U.S. adults. Groundbreaking results from a large randomized clinical trial, the Systolic Blood Pressure Intervention Trial-Memory Improvement through Nicotine Dosing (SPRINT-MIND) study, definitively demonstrated that intensive blood pressure control reduces the risk of cognitive decline and dementia.
In this study, researchers randomized over 8,600 individuals to an intensive blood pressure control regimen aimed at maintaining a systolic blood pressure under 120 mmHg or a standard regimen targeting a systolic pressure of less than 140 mmHg. Study participants were followed for eight years with cognitive evaluations by experts blinded to their treatment regimen. The study authors found that participants in the intensive blood pressure control group had a 19 percent lower rate of new MCI cases than the standard treatment group. Additionally, they had a 15 percent lower rate of combined MCI and all-cause dementia.
Having a concrete way to reduce your risk of MCI and dementia is empowering. The challenge is that because high blood pressure rarely causes symptoms, many Americans are unaware they are at risk, and fail to seek treatment (see “Treating High Blood Pressure”). Untreated high blood pressure can damage the arteries, heart, and, as the SPRINT-MIND study demonstrated, the brain as well.
The American Heart Association cautions that high blood pressure can increase the risk for cognitive impairment later in life, particularly for those individuals who have hypertension in middle age. This was underscored by results from a large study published in the June 2018 issue of the European Heart Journal. Using data from a British study population known as the Whitehall II cohort, French researchers examined data collected from 8,639 participants every five years between 1985 and 2015.
After adjusting for demographic factors including age, sex, ethnicity, and education, as well as health factors such as diabetes, obesity, poor diet, smoking, and physical activity, they observed that a systolic blood pressure over 130 represented a significant risk factor for dementia only in those individuals under the age of 60. That risk, however, grew the longer the individual lived with hypertension. When they adjusted for other cardiovascular diseases (e.g., heart disease and stroke), the relationship was slightly weaker but still existed. Experts say this study demonstrated two important points.
First, the dementia risk from high blood pressure doesn’t appear to be solely caused by end-organ damage (heart disease or stroke), as some patients under age 60 without other cardiovascular disease still had a heightened risk of dementia. Additionally, it demonstrates the importance of assessing blood pressure at an early age.
Living with high blood pressure also increases your odds of having a stroke—a major cause of vascular dementia. Managing high blood pressure and other risk factors that can lead to strokes can help preserve your brain health as you age. These risks include diabetes, high levels of “bad” LDL cholesterol, atrial fibrillation (A-fib), obesity, and smoking.
Modifying these risks not only prevents a stroke, but it also can lower dementia risk, as a Canadian stroke prevention program found. In addition to reducing new stroke diagnoses by nearly 38 percent in people ages 80 or older, the program—which promoted lifestyle interventions, the use of blood pressure medications, and better support from doctors—also reduced dementia diagnoses by more than 15 percent in this age group.
Lowering your stroke risks is key to protecting your cognitive health. Knowing the symptoms of stroke and getting immediate medical care can help you avoid irreparable cognitive damage.
While high blood pressure increases dementia risk, low blood pressure might also be problematic when it comes to cognitive health. A 2016 study found that people who experience a sudden drop in blood pressure when they stand up—a phenomenon called orthostatic hypotension—have a 15 percent increase in long-term risk of AD and other forms of dementia. The authors said orthostatic hypotension temporarily deprives the brain of oxygen-rich blood, which previous studies have shown can contribute to brain dysfunction. Lifestyle changes, such as drinking more water and wearing compression garments, may help you manage this condition.
The same explanation might account for why hypertension in older age—particularly 85 and older—may have a protective effect for dementia. As we age, our arteries become stiffer, making it harder to maintain adequate blood flow throughout the brain. Higher pressures in these older vessels may help keep the brain supplied with the oxygen and nutrient-rich blood it needs. However, this area is still being investigated.
Cardiovascular Disease. Brain and heart health are closely related. Despite just taking up 2 percent of our body weight, the brain consumes 20 percent of our oxygen and energy supplies, and it relies on the heart and blood vessels to deliver them. It comes as little surprise then that people with cardiovascular disease and heart conditions such as A-fib and congestive heart failure may be at significantly higher risk for cognitive impairment.
Cardiovascular disease weakens the heart and disrupts the supply of oxygen-rich blood to the brain. In particular, plaques formed from LDL cholesterol can narrow the carotid arteries that carry blood up either side of the neck, slowing or blocking blood flow to the brain. This is called carotid artery disease. The greater the disruption in blood flow, the greater the decline in cognitive function, research finds. Disrupted blood flow has been linked to poorer cognitive functioning, especially in the areas of attention and executive functions, such as decision-making and thinking.
For years, research has linked dementia with cardiovascular disease and its risk factors, like obesity, high blood pressure, high cholesterol, smoking, and high LDL cholesterol. More recently, researchers have begun to see the direct effects of these risk factors on the brain.
A recent study enrolled 346 individuals without a diagnosis of dementia at baseline, ages 45 to 64, and measured cardiovascular risk factors like a BMI of 30 or higher, smoking, high blood pressure, diabetes, and total cholesterol of 200 mg/dL or higher. They followed the study participants for 25 years, performing serial PET scans. They found that those individuals with a greater number of cardiovascular risk factors at the study outset had higher levels of beta-amyloid deposition in their brains later in life, regardless of whether they had a genetic risk for AD.
In a study called the Risk Reduction for Alzheimer’s Disease (rrAD) trial, researchers are looking at whether intensive pharmacologic control of cholesterol and blood pressure along with exercise might improve cognitive function.
The study involves over 640 individuals between the ages of 60 and 85 who are cognitively normal but at increased risk of dementia either because of lifestyle, health factors or family history. The participants are randomized to either usual care, intensive pharmacologic therapy for cholesterol and blood pressure control, exercise, or exercise and pharmacologic therapy. The study authors hypothesize that both exercise and intensive pharmacologic therapy will improve cognitive function while the combined regimen will provide even greater benefit. The study is expected to conclude in 2022, and the authors hope it will help guide future treatment for reducing the risks of AD and cardiovascular disease.
Kidney Disease. Our kidneys’ primary function is to filter the waste out of our bloodstream and help us eliminate it through the production of urine. Damage to the kidneys—for example from 
untreated diabetes or high blood pressure—can cause protein to leak into the urine. Excess protein in the urine is a warning sign of kidney damage, but it also may be a dementia alert.
In another analysis of data from the SPRINT-MIND study, researchers found that adults with evidence of compromised kidney function—a higher albumin to creatinine ratio (ACR)—had worse global cognitive function, executive function, memory, and attention than those with normal ACR. Similarly, adults with another sign of kidney disease—a lower filtration rate or GFR—had worse global cognitive function and memory than those with normal GFR. This same study was the basis for the American Heart Association’s recent lowering of the blood pressure measurements that define hypertension, as it found significant cardiovascular and kidney benefits associated with lower blood pressures.
What the precise underlying connection between kidney disease and dementia is remains to be seen, seen, but there are likely multiple factors involved. Both conditions share many of the same risk factors, such as diabetes, high blood pressure, and high cholesterol; and blood vessel abnormalities are a factor in both. Some researchers also suspect kidney damage might directly affect cognitive function, although they don’t know exactly how.
Depression and Alzheimer’s. Depression and Alzheimer’s have a complicated relationship: There is some evidence that depression is a risk factor for Alzheimer’s, but it also may be a prodrome in the early preclinical phase of Alzheimer’s. In any event, depression and Alzheimer’s share many of the same symptoms, and as many as 50 percent of people with Alzheimer’s suffer from depression.
Several large reviews of multiple studies have demonstrated that a history of depression may pose a risk for developing dementia, suggesting that treatment for depression has benefits beyond just treating symptoms. Earlier-life depression appears to have an association with dementia, conferring a two-fold or greater risk according to some research. At the same time, those depressive symptoms can mimic symptoms of mild or moderate Alzheimer’s, including apathy, social withdrawal, sleep problems, trouble concentrating, and impaired thinking. Distinguishing between the two can be challenging and reinforces the importance of seeking help from a health-care provider if you or someone you know is experiencing these symptoms.
Depression is a medical condition that can be treated. It’s important for people of every age to recognize the warning signs—which include feelings of hopelessness and helplessness, loss of appetite, and a lack of interest in activities they once enjoyed. Treatments such as antidepressant medications and talk therapy can help alleviate depression.
Poor Diet and Weight Gain. A diet high in fat and low in important nutrients can set off a cascade of events that ultimately contribute to Alzheimer’s. Unhealthy diets can lead to chemical changes in the brain, accumulation of excess abdominal fat, obesity, high blood pressure, and high insulin levels. These risk factors may, in turn, contribute to health conditions such as diabetes and stroke, which have been directly associated with increased Alzheimer’s risk.
A recent study demonstrated a strong association between a poor diet and lower cognitive performance. Researchers from Columbia University collected dietary intake information (by questionnaire) and blood samples from 330 cognitively normal individuals ages 65 and older. They found that individuals with what they termed an inflammation-related nutrient pattern (INP)—low intake of calcium, vitamins A, B1, B2, B3, B5, B6, D, E, folate, omega-3 polyunsaturated fatty acids and high intake of cholesterol—also had higher levels of the inflammatory markers C-reactive protein (CRP) and interleukin-6. Approximately five years later, they performed MRI scans and cognitive tests on the study participants. Controlling for factors such as age, sex, race, and ApoE genotype, they demonstrated two interesting findings. Those individuals with a higher INP also had smaller total brain volume and smaller gray matter volume (the part of the brain that is most affected by Alzheimer’s). Additionally, these participants had lower scores on cognitive tests assessing visuospatial function.
The authors conclude that “the magnitude of the effect of consuming a diet that yields a 1-unit higher INP score is comparable to that of 10 years of increasing age … [and these results suggest that] if the systemic environment is favorable, such as low systemic inflammation by following a healthy diet, individuals may have less AD-related brain and cognitive deficits.” By contrast, research has shown that a heart-healthy diet rich in fruits, vegetables, whole grains, fish, chicken, nuts, and legumes and low in saturated fats, red meat, and sugar may be associated with a lower risk of dementia.
Beverages also may play an important role. Two studies published in 2017 demonstrated that both sugary and artificially sweetened beverages are linked with cognitive function. In the first study published in Alzheimer’s and Dementia, researchers found a direct association between sugary beverage consumption, memory problems, and smaller brain volumes.
The second study, published in Stroke, found an increased risk for all dementia, Alzheimer’s, and stroke among people with a higher intake of artificially-sweetened beverages. Neither study proved a cause and effect, but the strong association reinforces the value in replacing these drinks with healthier options like water or tea. Choosing foods and beverages that maintain heart and brain health may have a protective effect, shielding against the cumulative damage that leads to dementia.
Sedentary Behavior. A poor diet is one contributor to weight gain and dementia. The other major contributor is sedentary behavior, which becomes increasingly more common in older age due to mobility-limiting conditions like arthritis. Adults ages 60 and over tend to spend 65 to 80 percent of their waking hours sitting—often parked in front of the TV. A lack of exercise could pose as great a risk for dementia as carrying the ApoE4 susceptibility gene, according to a study published January 2017, in the Journal of Alzheimer’s Disease. Getting the recommended 150 minutes of moderate activity each week could help combat this risk.
A recent study in the journal Neurology, moreover, showed that for women, being physically fit in midlife was associated with cognitive benefits decades later.
The study involved 191 Swedish women between the ages of 38 and 60 whose cardiovascular fitness level was assessed with a stepwise-increased maximal ergometer cycling test in 1968. The women were then followed with six serial neuropsychiatric examinations over the ensuing 44 years. The researchers found a strong association between higher fitness level and lower risk of subsequent dementia among the women when adjustments were made for socioeconomic, lifestyle, and medical confounders. Specifically, a high fitness level in middle age was associated with a 9.5-year delay in age at onset of dementia compared with a medium fitness level.
Smoking. Smoking is thought to affect memory by contributing to cardiovascular disease (a known risk factor for dementia), blood vessel damage, hardening of the arteries, and oxidative stress. Research has found that people who smoke are 30 to 50 percent more likely to develop AD or other forms of dementia than those who don’t smoke. Even if you don’t smoke, you put your mind and memory at risk by spending too much time around someone who does. People who are exposed to secondhand smoke face a 44 percent increased risk of dementia.
Pollution. Living too close to a busy highway or power plant might cause damage to your memory. The link between pollution exposure and diseases like asthma and lung cancer has been well established, but increasingly, research also is pointing to a link between pollution exposure and dementia risk.
Recently, investigators at the University of Southern California discovered that older women who lived in areas where they were exposed to high levels of fine pollution particles faced an 81 percent increased risk for global cognitive decline and a 92 percent increased risk for developing AD compared to women without these exposures. The risks were strongest among women who carry the ApoE4 gene variant, the authors wrote in the January 2017 issue of Translational Psychiatry.
Pollutants—especially the tiny particles released in car exhaust and power plant emissions—create oxidative stress that damages cells. Another group of researchers in Ontario, Canada, suggests that as many as one out of every 10 cases of dementia in people living within 50 yards of a major road could be attributed to pollution exposure. Skeptics have argued that other factors associated with living near busy roads, such as high noise pollution and stress, could be to blame.
However, a 2018 study published in the journal Environmental Research provided further insight into this question. Researchers measured noise levels and nitrous oxide levels at the residences of over 1,700 people living in a city in northern Sweden over a 15-year period. They found no association between noise pollution, independently or in combination with air pollution, and dementia. They did find a significant association between air pollution and dementia, confirming earlier findings. Although much more research needs to be done to confirm the link between pollution and dementia, the evidence collected so far provides a promising new direction for Alzheimer’s prevention efforts.
Lack of Mental and Social Stimulation. Leading a life lacking in mental stimulation can be detrimental to cognitive functioning and increase risk for dementia. Studies suggest that older adults who engage in mentally stimulating activities, such as board or card games, puzzles, classes, and social interactions are more likely to remain mentally sharp as they age.
Similarly, leading a solitary existence without regular social interaction has been implicated in observational studies as a risk factor for dementia. In one study published in JAMA Psychiatry, researchers found that among 823 participants, those who reported feeling lonely had twice the risk of developing AD compared with those who did not report loneliness. In a study of 2,249 women in California, researchers from Kaiser Permanente found that those women with a larger social network had a 26 percent lower likelihood of developing dementia than those with smaller social networks. Additionally, those women who reported daily contact with friends and family had a 50 percent lower risk of developing dementia than those without daily social contact.
It remains to be seen, however, whether reduced cognitive activities, social isolation, and feelings of loneliness represent true risk factors or early warning signs of impending AD. Nonetheless, many experts agree that finding a way to engage your mind and develop interpersonal relationships can keep you intellectually stimulated.
Stress. Stress is a true physiologic state mediated by the hormone cortisol. When we are in a stressful situation, our adrenal glands secrete cortisol, which revs up the “fight or flight” functions in our body—heart rate, blood pressure, and blood sugar (glucose) levels.
When a stressful event has passed, these functions return to baseline, but when the cause of stress doesn’t go away, these responses start to take their toll on our bodies. Research suggests that this may be the case for our brains and that chronic stress may accentuate memory problems. A surge in cortisol during stressful experiences might damage synapses in the brain and contribute to memory lapses as we age. Additionally, stress affects the immune system, which may play a role in the development of dementia.
Experts encourage anyone experiencing stress to consider adopting lifestyle strategies to mitigate it, including therapy and exercise.
The post 4. Alzheimer’s Disease appeared first on University Health News.
