The Alzheimer’s Association International Conference is the world’s largest meeting dedicated to advancing dementia research. Each year, researchers, clinicians and dementia experts come together to share groundbreaking research that will lead to prevention and treatment methods and improvements in the diagnosis of Alzheimer’s disease.
New data from prospective cohort studies involving more than 100,000 adults suggest that chronic constipation may lead to a decline in cognitive function. Researchers found that people with constipation who have bowel movements about every three days have significantly poorer cognitive performance compared to people who have daily bowel movements. This corresponds to an additional aging process of three years. Therefore, symptoms of abnormal bowel function should be watched for in elderly patients. It is estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, due to age-related factors such as a lack of fiber and exercise, as well as the use of constipating medications to treat other conditions. Chronic constipation – defined as bowel movements every three days or more often – is associated with long-term health problems such as inflammation, hormonal imbalance, anxiety and depression. This was the first study of its kind to also examine cognitive functions. Results show that frequency of bowel movements was associated with overall objective cognitive function and learning and working memory in an inverse J-shaped dose-response relationship. Preventive measures and to improve intestinal health can be a healthy diet with foods rich in fiber and polyphenols such as fruits, vegetables and whole grains, taking fiber supplements, drinking plenty of water daily and regular physical activity.
Volunteering protects the brain
Volunteering can protect the aging brain from cognitive decline and dementia, a recent study concludes. She studied a group of seniors and found that those who performed a volunteer role had better cognitive function – particularly in the areas of executive function and episodic memory – than peers who did not volunteer. This may be due to increased physical activity, greater social interaction, as well as higher mental engagement, among other factors, all of which are associated with better brain health. The researchers examined the volunteer habits of 2476 adults. After adjusting for relevant cofactors, those who volunteered had better baseline scores on average for executive function and verbal episodic memory compared with those who did not volunteer.
Better hearing slows cognitive loss
Patients with risk factors for dementia, such as diabetes and hypertension, show a 48% increase in cognitive decline three years after wearing a hearing aid. The results provide compelling evidence that treating hearing loss is an effective way to protect cognitive function later in life and potentially delay a dementia diagnosis in the long term, the study leader emphasized. Age-related hearing loss is very common and affects two-thirds of adults over the age of 60. It can be treated with hearing aids and audiological support services. The ACHIEVE study included 977 adults aged 70 to 84 years. They were recruited from older adults participating in the ongoing Atherosclerosis Risk in Communities (ARIC) trial and healthy volunteers. At baseline, the participants had similar hearing had no significant cognitive impairment. Researchers randomly assigned all participants to either a listening intervention group or an aging health education control group. Participants in the hearing intervention group attended four one-hour sessions with an audiologist every one to three weeks, received bilateral hearing aids, received regular education on the use of the devices, and learned strategies for hearing rehabilitation. The control group met regularly with a certified health educator who conducted the 10 Keys to Healthy Aging, an interactive health education program for adults aged 65. In the ARIC cohort, there was a significant 48% reduction in the hearing aid group compared to the control group. The hearing intervention was significantly associated with slower speech loss.
Gene scissors protect against neurodegenerative diseases
Two separate studies have examined how genes can increase the risk of developing neurodegenerative disease and how modifying them might reduce the risk or protect the brain from amyloid formation, which is thought to be the cause. The first study is from San Diego, where a gene-editing strategy is being developed to target the amyloid precursor protein (APP). This protein is known to cause an overproduction of beta-amyloid in the brain, resulting in plaque deposits that are a hallmark of the disease. The researchers investigated different ways to cut the APP and generated products that were either protective or pathological. They hoped to reduce beta-amyloid production while increasing neuroprotective effects. Testing the theory in mice, the researchers found that CRISPR treatment reduced the amount of beta-amyloid plaques and associated inflammatory markers. They also observed an increase in neuroprotective APP products and correction of deficits in behavior and nervous system function in the mice. They also observed no adverse side effects in normal mice. Future studies will be developed that aim to use APP-CRISPR processing in human trials.
Another study from Amsterdam looked at genes that contribute to Alzheimer’s risk, in particular APOE-e4. This gene is one of the most important risk factors for Alzheimer’s disease. However, its presence is not a guarantee that a person will get the disease. People with one copy have a two- to threefold higher risk of developing Alzheimer’s disease, and two copies increase the risk eight- to twelvefold.
Researchers have worked with an epigenome therapy platform that uses a CRISPR/dCas9 editing strategy to reduce APOE-e4. The platform’s lead candidate was found to reduce APOE-e4 levels in human induced pluripotent stem cell-derived miniature brains from an Alzheimer’s disease patient and in humanized mouse models. This was done without changing other APOE variants that are neutral or protective.
First tau aggregation inhibitor delivers promising results
Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), resulted in a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the phase III LUCIDITY trial. Neurofilament light chain (NfL) blood concentrations decreased by 93% over 12 months in participants receiving HMTM at the target dose of 16 mg/day compared with the control group. It correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores. NfL is among the best-studied biomarkers because it is off-target in a number of neurodegenerative diseases. In Alzheimer’s disease, it correlates with the severity of the disease and delineates the progressive damage to the neurons. Final 2-year data are expected to be released later this year.
No opioids in dementia
Administering opioids to older adults with dementia is associated with a significantly increased risk of death – especially in the first two weeks, when the risk is increased 11-fold, new research shows. Using Danish registries, researchers analyzed data on 75,471 adults in Denmark aged 65 and older who had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) received a prescription for an opioid. These “exposed” individuals were matched with 63,235 non-exposed individuals. In the exposed group, 33% died within 180 days of starting opioid therapy, compared with 6.4%. After adjustment for potential differences between groups, new use of an opioid was associated with a more than fourfold higher risk of death. New use of a strong opioid (morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, or fentanyl) was associated with a more than sixfold increase in the risk of death. Of those who had used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% among those not exposed. Here, the risk of death was eight times higher. For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of death. But even after 90 days, the risk remained elevated by a factor of two. Opioid therapy should therefore be considered for pain only if the benefits are likely to outweigh the risks in people with dementia.
Blood test for diagnosis at home
A simple blood test with a finger could determine if someone has Alzheimer’s and they could be treated as soon as possible. A team from the University of Gothenburg developed a test for three Alzheimer’s biomarkers – neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau181 and 217). To analyze the utility of these important biomarkers, researchers conducted a pilot study to investigate a novel method for their quantification in capillary and venous dry blood spots. The test involves dropping a small blood sample onto a blood spot card, where it dries and is stored at room temperature. They took both vein and finger samples from 77 patients at the ACE Alzheimer Center memory clinic in Barcelona. The dried blood samples were then extracted from the cards and NfL, GFAP, and p-tau181 and 217 were measured. All were detectable in the finger prick samples and correlated strongly with the results of standard blood collection. The pilot study demonstrated that there is a possibility for remote collection and measurement of Alzheimer’s disease biomarkers without frozen storage or extraordinary preparation or processing.
Congress: Alzheimer’s Association International Conference (AAIC)
InFo NEUROLOGY & PSYCHIATRY 2023; 21(4): 22-23 (published 8/19-23, ahead of print).
