Tag: alzheimer and dementia

Does smoking increase your risk for dementia and cognitive decline?

Photo by Abhishek Koli on Unsplash

Scientists from the Uniformed Services University (USU), Emory University and the University of Vermont have found that cigarette smoking is linked to increased lesions in the brain’s white matter, called white matter hyperintensities.  White matter hyperintensities, detected by MRI scan, are associated with cognitive decline and Alzheimer’s disease. These findings may help explain the link between smoking and increased rates of dementia and other forms of cognitive decline.

The study, “Associations of cigarette smoking with gray and white matter in the UK Biobank” was published online in the journal, Neuropsychopharmacology, https://rdcu.be/b1jPS

In June 2019, the Surgeons General of the Army, Navy, Air Force, and United States, released an open letter stating that tobacco use is a threat to the health and fitness of U.S. military forces and compromises readiness. This burden also extends to care provided by the Veterans Health Administration, which spends more than $2.5 billion annually on smoking-related care.  In response, Dr. Joshua Gray, assistant professor of Medical and Clinical Psychology and Neuroscience at USU, and colleagues, examined the association between cigarette smoking and brain structure. Cigarette smoking is associated with increased risk for myriad health consequences including increased risk for neuropsychiatric conditions, but research on the link between smoking and brain structure is limited.

Their study was the largest of its kind, including MRI brain scans from more than 17,000 individuals from the UK Biobank, a large cohort of volunteers from across the United Kingdom. They found that smoking was associated with smaller total gray and white matter volume, increased white matter lesions, and variation in specific gray matter regions and white matter tracts. By controlling for important variables that often co-occur with smoking, such as alcohol use, this study identified distinct associations between smoking and brain structure, highlighting potential mechanisms of risk for common neuropsychiatric consequences of smoking such as depression and dementia.

“Cigarette smoking is known to elevate risk for neuropsychiatric conditions such as depression and dementia. We found that smoking is associated with multiple aspects of brain structure, in particular with increased white matter lesions. White matter lesions are linked to many of the same neuropsychiatric diseases as smoking,” said Gray.  “Although further research is needed to understand to what extent smoking is a cause or consequence of these aspects of brain structure, our findings suggest a mechanism that links smoking to increased risk for dementia, depression, and other brain diseases.”

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New Alzheimer’s risk gene discovered

Photo by Aaron Andrew Ang

A new paper in the Journal of Neuropathology & Experimental Neurology finds a gene that may help explain a large part of the genetic risk for developing Alzheimer disease.

Late-onset Alzheimer disease, the most common form of the illness, is a devastating neurological condition with aspects of heritable risk that are incompletely understood. Unfortunately, the complexity of the human genome and shortcomings of earlier research are limiting factors, so that some genetic phenomena were not surveyed completely in prior studies. For example, there are many incompletely mapped genomic regions, and areas with repetitive sequences, that could not be studied previously.

Although Alzheimer’s is known to be largely heritable, a substantial proportion of the actual genetic risk for the disease has remained unexplained, despite extensive studies. This knowledge gap is known to researchers are the “missing (or hidden) heritability” problem. For example, while heritability explained 79% of late-onset Alzheimer disease risk in a Swedish twin study, common risk variants identified by pervious genetic studies explained only 20% to 50% of late-onset Alzheimer disease. In other words, a relatively large amount of genetic influence on late-onset Alzheimer disease risk was not explained by prior genetic studies.

Recent advances in sequencing technologies have enabled more comprehensive studies. Such developments allow for more precise and accurate identification of genetic material than was available in earlier gene variant studies.

In the present study, researchers analyzed Alzheimer’s Disease Sequencing Project data derived from over 10,000 people (research volunteers who agreed to have their genetic data evaluated in combination with their disease status), with the goal of identifying genetic variation associated with late-onset Alzheimer disease.

Preliminary results found evidence of late-onset Alzheimer disease -linked genetic variation within a segment of a gene called Mucin 6. Although the underlying mechanisms are mostly still unknown, researchers here believe that it’s possible to draw credible and testable hypotheses based on these results. For example, the genetic variant that was associated with Alzheimer’s disease risk may implicate a biochemical pathway in the brain that then represents a potential therapeutic target, a topic for future studies.

Corresponding authors were Yuriko Katsumata and Peter Nelson, both from the University of Kentucky. Dr. Nelson said of this study, “Our findings were made in a group of patients that is relatively small for a genetics study–some recent studies included hundreds of thousands of research subjects! That small sample size means two things: first, we should exercise caution and we need to make sure the phenomenon can be replicated in other groups; and second, it implies that there is a very large effect size–the genetic variation is strongly associated with the disease.”

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The paper, “Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene,” is available to the public on November 21, at one minute after midnight EST.