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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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: