Category Archives: Brain

Common Class of Medications Linked to AD, MCI Risk 

September 24, 2020

Several types of medications have been linked to mild cognitive impairment and Alzheimer’s disease (AD) risk in older patients over the years. A growing body of evidence points to drugs with anticholinergic effects as particularly dangerous for certain patient demographics. Emerging results from a recent study indicate that there may be a significant association between anticholinergic medications, AD biomarkers, and the incidence of mild cognitive impairment among cognitively normal older adults.

Anticholinergic Medications

Anticholinergic drugs have been widely used for a variety of medical conditions, ranging from allergies and the common cold to the treatment of hypertension. While certain anticholinergic medications require a prescription, others can be easily purchased over the counter.

This class of medications works by blocking acetylcholine, a neurotransmitter critical for memory function, from binding to receptors on certain nerve cells thereby inhibiting parasympathetic nerve impulses, which underlie involuntary muscle movements and bodily functions.

Examining the Relationship 

A team of researchers aimed to determine whether there were any cognitive consequences of anticholinergic medications (aCH) among a group of cognitively normal older patients and whether the interactive effects of genetic and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) risk factors had any influence.

Led by Alexandra Weigand at the UC San Diego School of Medicine, the team of researchers assessed 688 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative with a mean age of 73.5 years. None of the participants presented with any cognitive or memory problems at the time of study inception. Approximately one-third of patients was taking anticholinergic medications with an average of 4.7 aCH drugs per person. The study’s authors administered comprehensive cognitive tests annually for all participants.

Cox regression models were used to examine the risk of progression to mild cognitive impairment (MCI) over a 10-year period, while linear mixed effects models were utilized to evaluate 3-year rates of memory, executive, and language function as related to anticholinergic medication administration.

Association of Anticholinergic Drugs with AD and MCI

According to the study’s findings published in Neurology, participants with AD biomarkers who were taking anticholinergic medications were up to four times more likely to develop mild cognitive impairment than those lacking biomarkers and not taking aCH drugs. Similarly, participants who were at a genetic risk for Alzheimer’s disease who took anticholinergic medications were up to 2.5 times more likely to develop MCI than those without genetic risk factors who were not taking the medications.

Further, linear mixed effects models found that anticholinergic medications predicted a steeper slope of decline in memory and language functions. This was especially true for participants with AD risk factors, in which the effects were exacerbated.

Researchers believe that the association acts in a “double hit manner” :”In the first hit, Alzheimer’s biomarkers indicate that pathology has started to accumulate in and degenerate a small region called the basal forebrain that produces the chemical acetylcholine, which promotes thinking and memory. In the second hit, anticholinergic drugs further deplete the brain’s store of acetylcholine.” Overall, the combined effect can have a severe impact on a patient’s thinking and memory.

Clinical Implications 

The latest findings implicate an increased risk of incident MCI and cognitive decline as related to anticholinergic medications with effects significantly exacerbated in patients with existing genetic risk factors and CSF-based biomarkers. These results “underscore the adverse impact of these drugs on cognition and the need for deprescribing trials, particularly among individuals with elevated risk for AD,” the study’s authors wrote, emphasizing the importance of further evaluation to determine whether reductions in drug usage can lead to reductions in MCI progression.

However, the researchers also noted that anticholinergic medications were being taken at levels much higher than the lowest effective dose recommended for older patients; 57% of participants were taking twice the recommended dosage while 18% were taking at least four times the recommended dose.

As the findings suggest, reducing anticholinergic drug consumption may help delay age-related cognitive decline. According to senior author and associate professor at the UC San Diego School of Medicine Lisa Delano-Wood, PhD, the latest study “suggests that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills, especially for people at greater risk for Alzheimer’s disease.”

While the current evidence indicates a clear association between anticholinergic medications and cognitive effects, further research efforts are needed to determine whether these agents are able to accelerate cognitive changes or lead to the development of Alzheimer’s disease and other neurodegenerative disorders.

Living in Disadvantaged Neighborhoods Increases Risk for Brain Atrophy

July 1, 2020

Continuous scientific efforts contribute to the emergence of new information revealing the intricate complexities of neurological functions and their surprising connection to a wide range of external factors. Protecting neurological function can be made possible through the growing identification of risk factors for neurodegeneration during the aging process and can help inform new preventative protocols for dementia and cognitive decline.

The latest data suggest an association between living in a disadvantaged neighborhood and developing brain atrophy, or experiencing a decrease in the number of brain cells or connections over time. Neighborhood disadvantage functions as a social determinant of health, reflecting the education, income, employment, and quality of housing within a particular geographic area. As brain atrophy typically predisposes individuals to dementia and cognitive decline, this finding has significant implications for protecting cognitive function as individuals age.

Impact of Neighborhood on Neurological Health

Examining the impact of neighborhood socioeconomic disadvantage on brain volume in a cognitively unimpaired population, researchers conducted a study of over 950 individuals without a history of cognitive impairment in Wisconsin. In their cross-sectional study, the research team evaluated participants living in the most socioeconomically disadvantaged neighborhoods using data from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center to assess T1-weighted structural MRI scans.

At the beginning of the trial, participants were not cognitively impaired based on the National Institute on Aging-Alzheimer’s Association diagnostic criteria, however, the cohort was enriched for Alzheimer’s disease risk based on a family history of dementia.

Led by Amy J.H. Kind, MD, PhD from the University of Wisconsin, researchers calculated total hippocampal volume by combining both left and right measurements and based total brain tissue volume measures on total white and gray matter volumes. Additionally, they computed both the Area Deprivation Index – a geospatially determined index of neighborhood-level disadvantage – and cardiovascular disease risk indices for each participant. Linear regression models were used to test the relationships between neighborhood disadvantage and hippocampal and total brain tissue volume – as assessed by magnetic resonance imaging.

Neighborhood Disadvantage Linked to Loss of Brain Volume

Earlier this year, the team published their findings online in JAMA Neurology which reveal that living in socioeconomically disadvantaged neighborhoods was associated with markedly decreased hippocampal and total brain tissue volume. Other middle-aged and older adults who lived in areas with lesser disadvantage experienced comparatively lower risks of both neurological outcomes. Researchers found that individuals living in the most disadvantaged neighborhoods experienced a mean of 7 years of age-related hippocampal atrophy.

Furthermore, they also noted that men living in these neighborhoods experienced a higher risk for brain atrophy than women, although the reasons for this correlation remain unknown.

Cardiovascular risk was found to mediate the association in the case of total cerebral volume, indicating that neighborhood-level disadvantage may be associated with the two neurological outcomes via distinct biological pathways.

However, investigators acknowledged potential limitations of the trial which included the “enriched risk study cohort” – including older participants and those with a family history of dementia. They note that this population “might be particularly vulnerable to the deleterious effects of neighborhood-level disadvantage on the hippocampus.” In addition, the study’s findings reveal associations and not causality due to its cross-sectional, observational nature and require further validation.

Different from the implications of individual-level socioeconomic status on neurological function, this is the first study to reveal a robust association between neighborhood-level disadvantage and hippocampal volume, according to researchers. The latest findings indicate that neighborhood disadvantage may be associated with brain tissue volume throughout the aging process even in the absence of clinical cognitive impairment.

These results may suggest new population markers to leverage in future research studies; neighborhood-level disadvantage could be considered in clinical decision-making or used to guide public health efforts that support healthy brain aging in such geographic areas.

Brain Health Benefits of Yoga Practice

June 25, 2020

Despite being an exercise performed for many centuries in Eastern cultures, yoga has become increasingly popular over the past few decades among the Western population and alongside it, an exponential increase in research. People are drawn to the practice due to its multitude of mental and physical benefits, which include relaxation, muscle stretching, and an increased feeling of mindfulness. The health benefits of the physical exercise have been well established, yet there is a lack of research concerning the impact of yoga practice on the brain.

Today, yoga is the most popular form of complementary therapy practiced by over 13 million adults, with 58% of adults citing maintenance of health and well-being as their reason for practice per data reported by the National Center for Complementary and Integrative Health (NCCIH).

Recently, yoga has gained increased attention in the scientific community as well, as a research area of interest among exercise neuroscientists due to its promising potential therapeutic benefits with potential to combat widespread increases in the prevalence of age-related neurodegenerative diseases. Few studies have investigated the benefits of yoga on brain health yet recent research from the University of Illinois at Urbana-Champaign aims to analyze current literature related to yoga practice and its documented positive effects on brain structure and function.

Yoga and the Brain 

The team of researchers analyzed 11 studies of the relationships between yoga and brain health including the impact of yoga practice on brain structures, function, and cerebral blood flow. Of those, 5 trials engaged participants with no prior yoga experience in one or more yoga sessions per week over a period of 10 to 24 weeks to compare brain health before and after the intervention. Meanwhile, the remaining studies measured differences in brain health between participants who regularly practiced yoga and those who did not.

To determine variations in brain structure and health, each study utilized brain-imaging technologies including MRI, functional MRI, or single-photon emission computerized tomography to analyze the impact of Hatha yoga practice – which incorporates body movements, meditation, and breathing exercises.

Positive Neuroprotective Effects

Overall, researchers found that the studies reported a beneficial effect of yoga practice on both the structure and functioning of the hippocampus, amygdala, prefrontal cortex, cingulate cortex, and brain networks. As many of these regions are known to be related to age-related atrophy, the early evidence is promising and implicates that regular yoga practice could work to mitigate age-related and neurodegenerative diseases.

“For example, we see increases in the volume of the hippocampus with yoga practice,” lead author Neha Gothe from the University of Illinois said. “Many studies looking at the brain effects of aerobic exercise have shown a similar increase in hippocampus size over time.”

In addition, the review of the studies found that brain changes related to yoga practice were linked to improved cognitive performance and measures of emotional regulation.

Changes in Brain Structure

According to Gothe and her colleague Jessica Damoiseaux psychology professor at Wayne State University, many of the studies were exploratory and not conclusive. Despite this, the researchers suggest their findings underline important brain changes associated with regular yoga practice, including amygdala growth which may be directly related to improved emotional regulation in yoga practitioners.

“The prefrontal cortex, cingulate cortex and brain networks such as the default mode network also tend to be larger or more efficient in those who regularly practice yoga,” Damoiseaux explains. “Like the amygdala, the cingulate cortex is part of the limbic system, a circuit of structures that plays a key role in emotional regulation, learning, and memory.”

Regular yoga practice may help improve the cortisol stress response; researchers found that participants who practiced yoga for eight weeks had an attenuated cortisol response which also contributed to improved testing performance in cases of decision-making, task-switching, and attention span. Overall, researchers believe that the positive implications of yoga on brain structures and emotional regulation improve total brain functioning and thus, may have neuroprotective effects.

Not only does a regular yoga practice have well-documented physical health benefits, but it appears to also promote healthy brain function. However, researchers caution that more research is needed in this field to uncover the mechanisms underlying the evident brain changes, recommending large intervention studies that engage participants in yoga practice for long periods of time and allow for comparisons with other forms of exercise.

“The science is pointing to yoga being beneficial for healthy brain function, but we need more rigorous and well-controlled intervention studies to confirm these initial findings,” Damoiseaux concludes.