Are Common Drugs Causing Dementia and Alzheimer’s?
Choline falls into its own category as a nutrient. It is not one of the B vitamins (or replaceable by B vitamins) but works closely with them. In the body, choline is a precursor to acetylcholine and is a component of the phospholipid called phosphatidylcholine. Both are used by cells in the brain called cholinergic cells that oversee brain signals. But acetylcholine and these neurons face some very heavy challenges. One of them in the form of an enzyme called acetylcholinesterase.
Acetylcholinesterase is an enzyme in the body that breaks down acetylcholine. In healthy individuals, that’s no big deal. However, if this enzyme is over expressed, the essential acetylcholine isn’t available to help neuronal signals fire thoughtout the brain properly.
In the case of normal aging, you may notice the difference in slight memory gaps or some minor loss of a sense of balance. In extreme cases, whether the brain has been physically damaged, or conditions including Alzheimer’s, Parkinson’s, and Down syndrome there are real deficits of cholinergic cells, and as a result, less of the “connectivity” between the signals.
However, you may also face threats to the health of your brain that you weren’t even aware of, in the form of common over-the-counter drugs.
In fact, if you suffer from allergies, you’ll want to be very careful with diphenhydramine, commonly known by the brand name, Benadryl.
In an article published in the Journal of the American Medical Association Internal Medicine, researchers reported that diphenhydramine, along with drugs for overactive bladder and tricyclic antidepressants, had “anticholinergic” activity in the brain. That means they block the action of acetylcholine in the brain, which translates into memory loss, attention deficits, and slower motor skills. This wasn’t completely unknown before – it was accepted as one of the side effects of these medications. However, what has received more focus is that these conditions aren’t necessarily as benign or reversible as was once thought.
Other more recent work has found that anticholinergic medications (aCH) significantly increase the progression of mild cognitive impairment over time. These medications included tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics, medications prescribed for overactive bladder. After seven years, a follow-up exam of participants in this study found that 23 percent developed dementia and approximately 80 percent was due to Alzheimer’s.
One way to avoid these over-the-counter medications and the risks they bring is to find clinically studied alternatives, like curcumin blended with turmeric essential oil, Icelandic angelica extract for improved bladder function, and herbal anxiety relief like specific Echinacea angustifolia. These botanicals have the added benefits of not causing harm, but only working through pathways in the body and mind that reduce the risk of disease, rather than cause them.
Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015 Mar;175(3):401-7.
Importance: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.
Objective: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia.
Design, setting, and participants: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.
Exposures: Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time.
Main outcomes and measures: Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities.
Results: The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses.
Conclusions and relevance: Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.
Weigand AJ, Bondi MW, et al. Association of anticholinergic medication and AD biomarkers with incidence of MCI among cognitively normal older adults. Neurology. Sep 2020, 10.1212/WNL.0000000000010643; DOI: 10.1212/WNL.0000000000010643
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 ε4 genotype and CSF biomarker evidence of AD pathology were also assessed.
Results: aCH+ participants had increased risk of progression to MCI (HR = 1.42, p = .02), and there was a significant aCH x AD-risk interaction such that (aCH+)(ε4+) individuals showed greater than 2-fold increased risk (HR = 2.47, p < .001) for incident MCI relative to (aCH-)(ε4-), while (aCH+)(p-tau/Aß+) individuals demonstrated greater than 4-fold (HR = 4.25, p < .001) increased risk relative to (aCH-)(p-tau/Aß-). Linear mixed effects models revealed that aCH predicted a steeper slope of decline in memory (t = -2.31, p = .02) and language (t = -2.35, p = .02), with effects exacerbated in individuals with AD risk factors.
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.