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Anticholinergic drugs found to significantly increase risk of cognitive decline, especially among those with Alzheimer’s Disease biomarkers or genetic predisposition

Common Class of Drugs Linked to Increased Risk of Alzheimer’s Disease (UC San Diego release):

A team of scientists, led by researchers at University of California San Diego School of Medicine, report that a class of drugs used for a broad array of conditions, from allergies and colds to hypertension and urinary incontinence, may be associated with an increased risk of cognitive decline, particularly in older adults at greater risk for Alzheimer’s disease (AD) … cognitively normal study participants who were taking at least one anticholinergic drug at baseline were 47 percent more likely to develop mild cognitive impairment (MCI), often a precursor to dementia such as AD, while being tracked over a period of up to a decade compared to participants who did not take such drugs.

The scientists also looked at whether participants had biomarkers for AD in their cerebrospinal fluid, such as certain types of proteins, or a well-known genetic risk factor for AD. They found that participants with AD biomarkers who were taking anticholinergic drugs were four times more likely to develop MCI than persons lacking biomarkers and not taking the drugs.

Similarly, persons at genetic risk for AD who took anticholinergic drugs were approximately 2.5 times more likely to develop MCI than those without genetic risk factors and who were not taking the drugs.

“We believe this interaction between anticholinergic drugs and Alzheimer’s risk biomarkers acts in a ‘double hit’ manner,” said Weigand, the study’s first author. “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. This combined effect most significantly impacts a person’s thinking and memory.”

The Study:

Association of anticholinergic medication and AD biomarkers with incidence of MCI among cognitively normal older adults (Neurology). From the abstract:

  • Objective: To determine the cognitive consequences of anticholinergic medications (aCH) in cognitively normal older adults as well as interactive effects of genetic and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) risk factors.
  • Methods: 688 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative were evaluated (mean age = 73.5, 49.6% female). Cox regression examined risk of progression to mild cognitive impairment (MCI) over a 10-year period, and linear mixed effects models examined 3‑year rates of decline in memory, executive function, and language as a function of aCH. Interactions with APOE ?4 genotype and CSF biomarker evidence of AD pathology were also assessed.
  • Conclusions: aCH increased risk of incident MCI and cognitive decline, and effects were significantly enhanced among individuals with genetic risk factors and CSF-based AD pathophysiological markers. Findings underscore the adverse impact of aCH medications on cognition and the need for deprescribing trials, particularly among individuals with elevated risk for AD.

The Study in Context:

  • First, do no harm? Common anticholinergic meds seen to increase dementia risk
  • Study: 46.7 million Americans have Alzheimer’s Disease brain pathology today, so it’s urgent to prevent or at least delay progression to clinical disease
  • Solving the Brain Fitness Puzzle Is the Key to Self-Empowered Aging
  • Report: 35% of worldwide dementia cases could be prevented by modifying these 9 modifiable risk factors
  • A call to action: We need the right incentives to guide ethical innovation in neurotech and healthcare
Rethinking and Retooling Brain Health and Mental Health from SharpBrains

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Anticholinergic drugs found to significantly increase risk of cognitive decline, especially among those with Alzheimer’s Disease biomarkers or genetic predisposition


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