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Association of Anticholinergic Medication and AD Biomarkers with Incidence of MCI among Cognitively Normal Older Adults
Association of Anticholinergic Medication and AD Biomarkers with Incidence of MCI among Cognitively Normal Older Adults
Introduction:
Introduction:
Medications with anticholinergic properties have widespread use among the older adult population for a variety of conditions, including allergies, chronic pain, incontinence, psychiatric symptoms, and cardiac issues, although there use is under increased scrutiny given research demonstrating that such medications exacerbate cognitive concerns among older adults with cognitive impairment including mild cognitive impairment (MCI) and dementia. Questions remain, however, as to the risk that anticholinergic medications confer on the development of cognitive impairment amongst cognitively healthy older adults, and whether the presence of Alzheimer's disease (AD) risk markers increase this risk.
Methods:
Methods:
This study included 688 cognitively healthy older adults from the Alzheimer's Disease Neuroimaging Initiatve (ADNI) who had available medication data at baseline and longitudinal cognitive data. Cox regression examined risk for progression to MCI over a 10-year period and linear mixed effects models examined 3-year cognitive domain change as a function of anticholinergic medication use (ach+ vs ach-) and a continuous anticholinergic burden score integrating number of medications, dosage, and anticholinergic potency. Interactions with AD cerebrospinal fluid biomarkers and apolipoprotein E (APOE) genotype were also assessed.
Results:
Results:
Ach+ participants had a 1.47-fold increased risk of progression to MCI relative to ach- participants, and each point increase in the ach burden metric conferred a 1.5x increased risk for incident MCI. When ach+ interacted with APOE e4 status and CSF AD biomarker positivity, risk for incident MCI was increased by greater that 2-fold and nearly 5-fold, respectivley, relative to the ach-/AD risk- groups. Older adults who were ach+ declined at faster rates in terms of memory and langauge, but not executive function, relative to ach-, with these rates steeper in the context of AD risk markers.
Conclusions:
Conclusions:
1) Among our sample of cognitively healthy older adults from ADNI, the presence of at least one anticholinergic medication conferred significantly increased risk for incident MCI across a 10-year period.
2) Risk for MCI was increased as anticholinergic burden increased, and also increased in the context of positive AD biomarkers of APOE e4 status and AD CSF positivity.
3) The cognitive domains most affected by ach+ were memory and language, with executive function less impacted.
4) Further research examining these effects in minoritized populations is critical to understand the differential rates at which these medications are prescribed and their potential unique effects on cognition across demographic groups.
Citation: Weigand, A. J., Bondi, M. W., Thomas, K. R., Campbell, N. L., Galasko, D. R., Salmon, D. P., Sewell, D., Brewer, J. B., Feldman, H. H., Delano-Wood, L., & Alzheimer's Disease Neuroimaging Initiative (2020). Association of anticholinergic medications and AD biomarkers with incidence of MCI among cognitively normal older adults. Neurology, 95(16), e2295–e2304. https://doi.org/10.1212/WNL.0000000000010643
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