Leisure Activities Lower Blood Pressure in Alzheimer’s Caregivers

(Wolters Kluwer Health: Lippincott Williams and Wilkins) Going for a walk outside, reading, listening to music — these and other enjoyable activities can reduce blood pressure for elderly caregivers of spouses with Alzheimer’s disease, suggests a study in Psychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of the American Psychosomatic Society. The journal is published by Wolters Kluwer.

“Greater engagement in pleasant leisure activities was associated with lowered caregivers’ blood pressure over time,” according to the report by Brent T. Mausbach, PhD, of University of California San Diego and colleagues.

“Participation in pleasant leisure activities may have cardiovascular benefits for Alzheimer’s caregivers.”

The study included 126 caregivers enrolled in the UCSD Alzheimer’s Caregiver Study, a follow-up study evaluating associations between stress, coping, and cardiovascular risk in Alzheimer’s caregivers. The caregivers were 89 women and 37 men, average age 74 years, providing in-home care for a spouse with Alzheimer’s disease.

As part of annual interviews over five years, the caregivers provided information on how often they engaged in various pleasant leisure activities. These ratings were analyzed for association with blood pressure over time, with adjustment for demographic and health factors.

The caregivers reported high levels of enjoyable activities — most said they spent time outdoors, laughing, watching TV, listening to music, and reading or listening to stories. About half of caregivers said they exercised frequently.

Caregivers who more frequently engaged in pleasant leisure activities had lower mean arterial blood pressure (a measure of average blood pressure). In follow-up analyses, these activities were associated with a significant reduction in diastolic pressure (the second, lower blood pressure number), although not in systolic pressure (the first, higher number).

As expected, caregivers who exercised more frequently had lower blood pressure. However, other types of “more sedentary, reflective” activities also led to reduced blood pressure. These included reading, listening to music, shopping, and recalling past events.

Blood pressure also decreased after nursing home placement or death of the person with Alzheimer’s disease. That was consistent with previous studies showing that caregivers’ health improves after their caregiving duties end.

Being a caregiver for a disabled loved one is a highly stressful experience, associated with an increased risk of cardiovascular disease and death. Stress may contribute to high blood pressure, which is the strongest risk factor for cardiovascular disease. The new results suggest that leisure activities are a behavioral factor that can prevent the development of high blood pressure in Alzheimer’s caregivers.

Dr. Mausbach notes that the study assessed both the frequency and enjoyment of activities. The premise is that rather than recommending certain activities to everyone, it’s important for caregivers to enjoy the activities they do to receive benefit. While the study can’t determine how many activities people should do,

“We believe three to four enjoyed activities each week could have a modest impact on an individual’s blood pressure,” Dr. Mausbach commented.

“From there, the more an individual can do, the better the impact.”

The researchers have been conducting a clinical trial to examine the effect of a therapy to increase pleasant leisure activities.

“We recognize caregivers may have a difficult time engaging in pleasant leisure activities because they are busy with their caregiving duties,” said Dr. Mausbach.

“So we work with caregivers to find activities they can more confidently engage in even when their spouse is present. We also help them monitor their use of time so they know the times during the day when they are most capable of doing activities. Further, if caregivers use respite services, they are in a perfect position to use some of their respite time to engage in these activities.”

Citation

https://www.sciencedaily.com/releases/2017/06/170623100708.htm

Journal Reference:

Brent T. Mausbach, Rosa Romero-Moreno, Taylor Bos, Roland von Känel, Michael G Ziegler, Matthew A. Allison, Paul J. Mills, Joel E. Dimsdale, Sonia Ancoli-Israel, Andrés Losada, María Márquez-González, Thomas L. Patterson, Igor Grant. Engagement in pleasant leisure activities and blood pressure. Psychosomatic Medicine, 2017; 1 DOI: 10.1097/PSY.0000000000000497

 

Anti-epilepsy Drug Restores Normal Brain Activity in Mild Alzheimer’s Disease

(Beth Israel Deaconess Medical Center) In the last decade, mounting evidence has linked seizure-like activity in the brain to some of the cognitive decline seen in patients with Alzheimer’s disease. Patients with Alzheimer’s disease have an increased risk of epilepsy and nearly half may experience subclinical epileptic activity — disrupted electrical activity in the brain that doesn’t result in a seizure but which can be measured by electroencephalogram (EEG) or other brain scan technology.

In a recent feasibility study, clinician-scientists at Beth Israel Deaconess Medical Center (BIDMC) tested an anti-epileptic drug for its potential impact on the brain activity of patients with mild Alzheimer’s disease. The team, led by Daniel Z. Press, MD, of the Berenson-Allen Center for Non-invasive Brain Stimulation at BIDMC, documented changes in patients’ EEGs that suggest the drug could have a beneficial effect. The research was published in the Journal of Alzheimer’s Disease.

“In the field of Alzheimer’s disease research, there has been a major search for drugs to slow its progression,” said Press, an Instructor of Neurology in the Cognitive Neurology Unit at BIDMC and an Associate Professor of Neurology at Harvard Medical School.

“If this abnormal electrical activity is leading to more damage, then suppressing it could potentially slow the progression of the disease.”

In this double-blind within-subject study, a small group of patients with mild Alzheimer’s disease visited BIDMC three times. At each visit, patients were given a baseline (EEG) to measure the electrical activity in the brain. Next, patients were given injections containing either inactive placebo or the anti-seizure drug levetiracetam, at either a low dose (2.5 mg/kg) or a higher dose (7.5 mg/kg). Neither patients nor medical professionals knew which injections patients were receiving, but each patient eventually got one of each type, in a random order.

After receiving the injection, patients underwent another EEG, then magnetic resonance imaging (MRI) — which measures blood flow in the brain, another way to quantify brain activity and determine where in the brain it is taking place. Finally, patients took a standardized cognitive test, designed to measure memory, executive functioning, naming, visuospatial ability and semantic function — capabilities all affected by Alzheimer’s disease.

In the seven patients able to complete the study protocol successfully, Press and colleagues analyzed changes in their EEGs. (Blood flow analysis from the MRI data is still underway.) Overall, higher doses of the anti-seizure drug appeared to normalize abnormalities seen in the patients’ EEG profiles. That is, researchers saw overall increases in brain wave frequencies that had been abnormally low in Alzheimer’s disease patients prior to receiving the higher dose of levetiracetam, and, likewise, saw decreases in those that had been abnormally high.

“It’s worth noting, we did not demonstrate any improvement in cognitive function after a single dose of medication in this study,” said Press.

“It’s too early to use the drug widely, but we’re preparing for a larger, longer study.”

The risk of developing Alzheimer’s disease increases sharply with age. Today, it affects more than 5 million Americans, a figure that is projected to reach 16 million by 2050 as the population ages. In recent years, researchers have focused on developing techniques to clear the brain of amyloid and tau protein plaques that build up and wreak havoc in the brains of patients with Alzheimer’s disease.

“These strategies have not led to new therapies to date,” said Press.

“There have been a lot of disappointments. So our findings represent an interesting new avenue.”

Citation

https://www.sciencedaily.com/releases/2017/06/170623131512.htm

Story Source:

Materials provided by Beth Israel Deaconess Medical Center. Note: Content may be edited for style and length.

Copyright 2017 ScienceDaily or by third parties, where indicated.

 

Alzheimer’s Disease Study Links Brain Health and Physical Activity

(Journal of Alzheimer’s Disease) People at risk for Alzheimer’s disease who do more moderate-intensity physical activity, but not light-intensity physical activity, are more likely to have healthy patterns of glucose metabolism in their brain, according to a new UW-Madison study.

Results of the research were published today online in Journal of Alzheimer’s Disease. Senior author Dr. Ozioma Okonkwo, assistant professor of medicine, is a researcher at the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Alzheimer’s Institute at the UW School of Medicine and Public Health.

First author Ryan Dougherty is a graduate student studying under the direction of Dr. Dane B. Cook, professor of kinesiology and a co-author of the study, and Dr. Okonkwo. The research involved 93 members of the Wisconsin Registry for Alzheimer’s Prevention (WRAP), which with more than 1,500 registrants is the largest parental history Alzheimer’s risk study group in the world.

Researchers used accelerometers to measure the daily physical activity of participants, all of whom are in late middle-age and at high genetic risk for Alzheimer’s disease, but presently show no cognitive impairment. Activity levels were measured for one week, quantified, and analyzed. This approach allowed scientists to determine the amount of time each subject spent engaged in light, moderate, and vigorous levels of physical activity.

Light physical activity is equivalent to walking slowly, while moderate is equivalent to a brisk walk and vigorous a strenuous run. Data on the intensities of physical activity were then statistically analyzed to determine how they corresponded with glucose metabolism—a measure of neuronal health and activity—in areas of the brain known to have depressed glucose metabolism in people with Alzheimer’s disease. To measure brain glucose metabolism, researchers used a specialized imaging technique called 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).

Moderate physical activity was associated with healthier (greater levels of) glucose metabolism in all brain regions analyzed. Researchers noted a step-wise benefit: subjects who spent at least 68 minutes per day engaged in moderate physical activity showed better glucose metabolism profiles than those who spent less time.

“This study has implications for guiding exercise ‘prescriptions’ that could help protect the brain from Alzheimer’s disease,” said Dougherty.

“While many people become discouraged about Alzheimer’s disease because they feel there’s little they can do to protect against it, these results suggest that engaging in moderate physical activity may slow down the progression of the disease.”

“Seeing a quantifiable connection between moderate physical activity and brain health is an exciting first step,” said Okonkwo.

He explained that ongoing research is focusing on better elucidating the neuroprotective effect of exercise against Alzheimer’s disease. To investigate this further, the team is recruiting individuals with concerns about their memory for a national clinical trial called EXERT to test whether physical exercise can slow the progression of early memory problems caused by Alzheimer’s disease. For more information or to volunteer, contact exercise physiologist Beth Jeanes at 608-265-5752 or by email at emjeanes@medicine.wisc.edu.

The Wisconsin Alzheimer’s Disease Research Center (ADRC) and The Wisconsin Alzheimer’s Institute (WAI) are two collaborative groups working under the UW Initiative to End Alzheimer’s in leading-edge research, education and outreach programs.

The study was supported by the National Institutes of Health, Veterans Administration, Alzheimer’s Association, Wisconsin Alumni Research Foundation, Helen Bader Foundation, Northwestern Mutual Foundation, and Extendicare Foundation.

Citation

http://www.j-alz.com/content/alzheimers-disease-study-links-brain-health-and-physical-activity

Journal of Alzheimer’s Disease is published by IOS Press

Copyright © 2017

 

Vegetarian Diets Almost Twice as Effective in Reducing Body Weight, Study Finds

(Taylor & Francis) Dieters who go vegetarian not only lose weight more effectively than those on conventional low-calorie diets but also improve their metabolism by reducing muscle fat, a new study published in the Journal of the American College of Nutrition has found.

Losing muscle fat improves glucose and lipid metabolism so this finding is particularly important for people with metabolic syndrome and type 2 diabetes, says lead author, Dr. Hana Kahleová, Director of Clinical Research at the Physicians Committee for Responsible Medicine in Washington DC.

Seventy-four subjects with type 2 diabetes were randomly assigned to follow either a vegetarian diet or a conventional anti-diabetic diet. The vegetarian diet consisted of vegetables, grains, legumes, fruits and nuts, with animal products limited to a maximum of one portion of low-fat yoghurt per day; the conventional diabetic diet followed the official recommendations of the European Association for the Study of Diabetes (EASD). Both diets were restricted by 500 kilocalories per day compared to an isocaloric intake for each individual.

The vegetarian diet was found to be almost twice as effective in reducing body weight, resulting in an average loss of 6.2kg compared to 3.2kg for the conventional diet.

Using magnetic resonance imaging, Dr. Kahleová and colleagues then studied adipose (fat-storage) tissue in the subjects’ thighs to see how the two different diets had affected subcutaneous, subfascial and intramuscular fat (that is, fat under the skin, on the surface of muscles and inside muscles).

They found that both diets caused a similar reduction in subcutaneous fat. However, subfascial fat was only reduced in response to the vegetarian diet, and intramuscular fat was more greatly reduced by the vegetarian diet.

This is important as increased subfascial fat in patients with type 2 diabetes has been associated with insulin resistance, so reducing it could have a beneficial effect on glucose metabolism. In addition, reducing intramuscular fat could help improve muscular strength and mobility, particularly in older people with diabetes.

Dr. Kahleová said: “Vegetarian diets proved to be the most effective diets for weight loss. However, we also showed that a vegetarian diet is much more effective at reducing muscle fat, thus improving metabolism.

This finding is important for people who are trying to lose weight, including those suffering from metabolic syndrome and/or type 2 diabetes. But it is also relevant to anyone who takes their weight management seriously and wants to stay lean and healthy.”

Citation

Taylor & Francis. “Vegetarian diets almost twice as effective in reducing body weight, study finds.” ScienceDaily. ScienceDaily, 12 June 2017. <www.sciencedaily.com/releases/2017/06/170612094458.htm>.

Story Source:

Materials provided by Taylor & Francis. Note: Content may be edited for style and length.

Journal Reference:

Hana Kahleova, Marta Klementova, Vit Herynek, Antonin Skoch, Stepan Herynek, Martin Hill, Andrea Mari, Terezie Pelikanova. The Effect of a Vegetarian vs Conventional Hypocaloric Diabetic Diet on Thigh Adipose Tissue Distribution in Subjects with Type 2 Diabetes: A Randomized Study. Journal of the American College of Nutrition, 2017; 1 DOI: 10.1080/07315724.2017.1302367

Copyright 2017 ScienceDaily or by third parties, where indicated.

 

Researchers Identify Potential Biomarker for Alzheimer’s Disease

(Boston University Medical Center) In one of the largest studies to date to use metabolomics, the study of compounds that are created through various chemical reactions in the body, researchers have been able to identify new circulating compounds associated with the risk of developing dementia and Alzheimer’s disease (AD).

The findings, which appear in the journal Alzheimer and Dementia, point to new biological pathways that may be implicated in AD and could serve as biomarkers for risk of the disease.

AD is the most common form of dementia responsible for a slow and progressive deterioration of memory and leads to frailty and dependence in elderly people. Despite ongoing research effort and improved knowledge about the disease, there is currently no effective preventive or curative treatment for AD, which could result in a public health crisis given the continuous aging of populations worldwide.

Using data from the Framingham Heart Study (FHS), researchers from Boston University School of Medicine (BUSM), observed an association specifically between levels of anthranillic acid measured in the plasma and a higher risk of developing dementia and AD after 10 years of follow-up.

Although the researchers are cautious about their results, they identify several findings they find promising.

“First anthranilic acid is produced during the degradation of tryptophan, an essential amino acid. Interestingly, other compounds produced through the same reactions have been reported as protective or deleterious for neurons and could constitute valuable drug targets.

Second, this potential marker could also be used to identify groups of persons at higher risk of developing dementia, which could improve the efficiency of clinical trials and in the future, detect persons that would benefit the most from a preventive treatment,” explained co-corresponding author Sudha Seshadri, MD, professor of neurology at BUSM and FHS senior investigator.

From a methodological point of view, this study is one of the first to use a prospective cohort such as the FHS to search for compounds associated with the risk of developing AD and dementia.

“As the field of AD epidemiology is only beginning to integrate the metabolomics approach, it is likely that fruitful collaborations and innovative ways to analyze these data will follow,” said co-corresponding author Vincent Chouraki, MD, PhD, former research fellow from BUSM and now assistant professor in epidemiology at Lille University School of Medicine in France.

Citation

https://www.bumc.bu.edu/busm/2017/06/12/ researchers-identify-potential-biomarker-for-alzheimers-disease/

Journal Reference:

Vincent Chouraki, Sarah R. Preis, Qiong Yang, Alexa Beiser, Shuo Li, Martin G. Larson, Galit Weinstein, Thomas J. Wang, Robert E. Gerszten, Ramachandran S. Vasan, Sudha Seshadri. Association of amine biomarkers with incident dementia and Alzheimer’s disease in the Framingham Study. Alzheimer’s & Dementia, 2017; DOI: 10.1016/j.jalz.2017.04.009

Copyright Boston University School of Medicine

 

Alzheimer’s Disease: Federal Action Update

(Alzheimer’s Association) On May 4, the U.S. House of Representatives voted 217-213 to pass the American Health Care Act (AHCA), which would repeal and replace large parts of the Affordable Care Act (ACA). The U.S. Senate is now working on its own legislative proposal to reform the health care system, with the goal of passing a bill by August.

The Alzheimer’s Association and the Alzheimer’s Impact Movement (AIM) have called on Congress to preserve access to Medicaid services for individuals living with Alzheimer’s and other dementias and provide affordable access to health care for individuals with pre-existing conditions like Alzheimer’s. Medicaid is the only public program that covers the long-term nursing home stays that most people with dementia require in the late stages of the disease. Medicaid also covers home and community-based services which are critical for people with dementia, particularly in the early and middle stages of the disease.

As members of the U.S. Senate work to draft this legislation, they need to hear from you.

Today, more than one in four seniors with Alzheimer’s and other dementias are on Medicaid. Any legislation must preserve this essential safety net. Additionally, legislation must ensure that individuals with Alzheimer’s and other dementias have pre-existing condition protections that safeguard continued access to affordable health care.

Tell your Senators to support individuals living with Alzheimer’s now!


The Alzheimer’s Association is the world’s leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s disease®.

Alzheimer’s Association National Office, 225 N. Michigan Ave., Fl. 17, Chicago, IL 60601
www.alz.org | 800.272.3900

Citation

© 2017 Alzheimer’s Association. All rights reserved.

 

Sleep Apnea and Dementia

(BrightFocus Foundation)

It took a fender bender to bring Bill* to his primary care clinician for evaluation. “Maybe I snoozed! I woke up on the embankment and I’m lucky nobody was hurt.”

In addition to driving difficulties, Bill also described increasing forgetfulness, fatigue, and confusion over the past year. Despite his young age of 65, Bill’s primary care physician referred him to the Memory Clinic, where additional history was obtained.

Bill reported that his mood was low, his weight was increasing, his blood pressure was out of control, and he was constantly dragging. He usually couldn’t get through the day without sneaking a nap. He and his wife agreed that he was spending plenty of time in bed each night. Bill’s wife admitted that she sometimes would move to the living room recliner because of Bill’s loud snoring and gasping.

*The name and details were changed to protect privacy.

Bill’s little motor vehicle accident was a blessing in disguise. He was referred for a sleep study which revealed severe obstructive sleep apnea, a potentially treatable medical condition.

Bill was suffering from a common disorder that, like radio drama’s famous Shadow, has “the power to cloud men’s minds.”

And women’s minds, too, although researchers think women’s higher progesterone levels may stimulate breathing and reduce the likelihood of apnea. Sleep apnea is considered a risk factor for dementia. People with sleep apnea have been shown not only to have impaired memory and executive function, but also biomarker changes that are associated with Alzheimer’s disease.

What is Sleep Apnea?

Sleep apnea, which means failure to breathe during sleep, can be obstructive or non-obstructive. Non-obstructive or “central” apnea occurs when the brain fails to signal the breathing muscles that it’s time to get active. In obstructive apnea, breathing fails because of a relaxed airway that fails to open up despite the brain’s insistence.

Eventually, sometimes after more than a minute without breathing, the brain sounds its alarms urgently enough to jolt the muscles of breathing back into action. Sometimes this wakes the sleeper, but more often the periods of apnea and gasping serve only to rob sleep of its restful and restorative quality.

A respiratory infection or excessive alcohol use can also interfere with breathing during sleep. Chronic and severe apnea, however, is a prolonged, debilitating condition.

Risk Factors

Older age, with its loss of muscle tone, is an important risk factor for sleep apnea. Men have sleep apnea more often than women, although women can also be affected. Obesity, smoking, excessive use of sedatives or alcohol, or a positive family history of sleep apnea are additional risk factors. Also, more than half of people with Down syndrome have sleep-related breathing problems.

The Risks of Untreated Sleep Apnea

One of Shakespeare’s characters called sleep the “chief nourisher in life’s feast.” He was right! During sleep, the body actively repairs and restores itself. Lack of oxygen during sleep interferes with memory formation, blood pressure regulation, and weight control.

Untreated apnea is associated with increased risk for dementia, stroke or heart attack. In one study, persons with sleep apnea had a 30 percent higher risk of heart attack or death than those without apnea.

Treatment

Treatment of obstructive sleep apnea can be more straightforward than treatment of apnea that is central or mixed (with both central and obstructive problems). Simple steps such as limiting alcohol, smoking, sedatives and muscle relaxants; losing weight; sleeping on one’s side (sometimes reinforced by sewing a tennis ball on the back of the pajamas or wearing a “fanny pack” to bed) or elevating the head of the bed can help. Physical training has been shown to reduce sleep apnea even in the absence of weight loss.

CPAP

Bill’s apnea was serious enough to require more intensive treatment, so he was prescribed continuous positive airway pressure (CPAP), a treatment that uses an air pump, tube, and mask to inflate the sleeper’s collapsed airway. Testing of patients has shown that CPAP reduces the neuropsychological deficits associated with sleep apnea.

BiPAP and Auto CPAP

If CPAP had been too uncomfortable for Bill, as it is for some people, he would still have treatment alternatives. Variable positive airway pressure (BiPAP), and “Auto CPAP,” are better tolerated by some because they respond to the sleeper’s natural breathing to fine-tune the delivery of air through the mask.

Special Dental Appliances

Specially trained dentists can treat apnea by preparing a retainer-like device that pushes the lower jaw forward in order to keep the airway open.

Surgical Procedures

Special surgical procedures, an option that many experts suggest trying to avoid, can also increase the openness of the airway. Experimental approaches under investigation include a device that stimulates the hypoglossal nerve (a cranial nerve that activates certain muscles of the tongue).

A few months after Bill started treatment with CPAP, he returned for a primary care appointment. His blood pressure was better controlled, his energy was greatly increased, and he no longer was napping. He felt more rested every morning and clearer-headed throughout the day.

“Okay, my wife makes occasional bedtime jokes about my ‘scuba gear’, but … I’m not keeping her awake at night and I feel so much healthier every morning.”

Citation

http://www.brightfocus.org/alzheimers/article/sleep-apnea-and-dementia

by James M. Ellison, MD, MPH

Further Reading:

Ferini-Strambi L, Lombardi GE, Marelli S, et al. Neurological Deficits in Obstructive Sleep Apnea.
Curr Treat Options Neurol. 2017 Apr;19(4):16.

Hill EA. Obstructive sleep apnoea/hypopnoea syndrome in adults with Down syndrome.
Breathe (Sheff). 2016;12(4):e91-e96. doi: 10.1183/20734735.012116.

Javaheri S, Barbe F, Campos-Rodriguez F, et al. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017 Feb 21;69(7):841-858. doi: 10.1016/j.jacc.2016.11.069.

Liguori C, Mercuri NB, Izzi F, et al. Obstructive sleep apnea is associated with early but possibly modifiable Alzheimer’s Disease changes. Sleep. 2017 Jan 28. doi: 10.1093/sleep/zsx011. [Epub ahead of print]

Kerner NA, Roose SP, Pelton GH, et al. Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study. Am J Geriatr Psychiatry. 2017 Mar;25(3):316-325. doi: 10.1016/j.jagp.2016

Copyright BrightFocus Foundation

 

Researchers Discover What May be Earliest Stage of Alzheimer’s

(University of Southern California) Older adults with elevated levels of brain-clogging plaques—but otherwise normal cognition—experience faster mental decline suggestive of Alzheimer’s disease, according to a new study led by the Keck School of Medicine of USC that looked at 10 years of data.

Just about all researchers see amyloid plaques as a risk factor for Alzheimer’s.

However, this study presents the toxic, sticky protein as part of the disease—the earliest precursor before symptoms arise.

“To have the greatest impact on the disease, we need to intervene against amyloid, the basic molecular cause, as early as possible,” said Paul Aisen, senior author of the study and director of the USC Alzheimer’s Therapeutic Research Institute (ATRI) at the Keck School of Medicine.

“This study is a significant step toward the idea that elevated amyloid levels are an early stage of Alzheimer’s, an appropriate stage for anti-amyloid therapy.”

Notably, the incubation period with elevated amyloid plaques—the asymptomatic stage—can last longer than the dementia stage.

“This study is trying to support the concept that the disease starts before symptoms, which lays the groundwork for conducting early interventions,” said Michael Donohue, lead author of the study and an associate professor of neurology at USC ATRI.

The researchers likened amyloid plaque in the brain to cholesterol in the blood. Both are warning signs with few outward manifestations until a catastrophic event occurs. Treating the symptoms can fend off the resulting malady—Alzheimer’s or a heart attack—the effects of which may be irreversible and too late to treat.

“We’ve learned that intervening before the heart attack is a much more powerful approach to treating the problem,” Donohue said.

Aisen, Donohue and others hope that removing amyloid at the preclinical stage will slow the onset of Alzheimer’s or even stop it.

The Amyloid Problem

One in three people over 65 have elevated amyloid in the brain, Aisen noted, and the study indicates that most people with elevated amyloid will progress to symptomatic Alzheimer’s within 10 years.

If Alzheimer’s prevalence estimates were to include this “preclinical stage” before symptoms arise, the number of those affected would more than double from the current estimate of 5.4 million Americans, the study stated.

Published in The Journal of the American Medical Association on June 13, the study uses 10 years of data from the Alzheimer’s Disease Neuroimaging Initiative, an exploration of the biomarkers that presage Alzheimer’s. USC ATRI is the coordinating center of this North American investigation. Aisen co-directs its clinical core.

USC plays a leading role in the only two anti-amyloid studies focused on the early, preclinical stage of sporadic Alzheimer’s: The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (the A4 Study) and the EARLY Trial, Aisen said.

“We need more studies looking at people before they have Alzheimer’s symptoms,” Aisen said.

“The reason many promising drug treatments have failed to date is because they intervened at the end-stage of the disease when it’s too late. The time to intervene is when the brain is still functioning well—when people are asymptomatic.”

Although elevated amyloid is associated with subsequent cognitive decline, the study did not prove a causal relationship.

For years, researchers have acknowledged age is the biggest risk factor when it comes to Alzheimer’s. For more than 90 percent of people with Alzheimer’s, symptoms do not appear until after age 60, according to the Centers for Disease Control and Prevention.

In 2014, about 46 million adults living in the United States—15 percent of the population—were 65 or older. By 2050, that number is expected to expand to 88 million or 22 percent of the population.

The Tipping Point

Researchers measured amyloid levels in 445 cognitively normal people in the United States and Canada via cerebrospinal fluid taps or positron emission tomography (PET) scans: 242 had normal amyloid levels and 202 had elevated amyloid levels. Cognitive tests were performed on the participants, who had an average age of 74.

Although the observation period lasted 10 years, each participant, on average, was observed for three years. The maximum follow-up was 10 years.

The elevated amyloid group was older and less educated. Additionally, a larger proportion of this group carried at least one copy of the ApoE4 gene, which increases the odds that someone will develop Alzheimer’s.

Based on global cognition scores, at the four-year mark, 32 percent of people with elevated amyloid had developed symptoms consistent with the early stage of Alzheimer’s disease. In comparison, only 15 percent of participants with normal amyloid showed a substantial decline in cognition.

Analyzing a smaller sample size at year 10, researchers noted that 88 percent of people with elevated amyloid were projected to show significant mental decline based on global cognitive tests. Comparatively, just 29 percent of people with normal amyloid showed cognitive decline.

Alzheimer’s Disease Research Worldwide

Alzheimer’s was recently a disease that could be diagnosed only after death with an autopsy.

Aisen and the researchers at USC ATRI have developed ways to identify early signs of Alzheimer’s by creating a set of cognitive tests called the Preclinical Alzheimer Cognitive Composite. This battery of tests and variations of it are widely used to detect Alzheimer’s before dementia symptoms emerge, Aisen said.

“Our outcome measures are becoming the standard for early Alzheimer’s disease intervention studies,” Aisen said.

“Drug companies will not invest in early intervention studies without a regulatory pathway forward. ATRI and USC are building a framework for drug development in Alzheimer’s disease.”

As a research institution devoted to promoting health across the life span, USC has more than 70 researchers dedicated to the prevention, treatment and potential cure of Alzheimer’s disease.