BACKGROUND: Acetylcholinesterase inhibitors and memantine are recommended

therapies for dementia of the Alzheimer type (DAT).

However, many patients with the clinical diagnosis of DAT do not exhibit

Alzheimer's disease (AD) pathology. It remains unclear whether these

patients benefit from treatment with these drugs.

 

METHOD: This cohort study used longitudinal data from The National Alzheimer’s

Coordinating Center (NACC) Data Set. Eligibility criteria included clinical

diagnosis of DAT, age 51-90 years, symptoms onset < 8 years, dementia

diagnosis at baseline or during follow-up, start of symptomatic drug

treatment within 15 months after baseline or no treatment, and available

post-mortem neuropathology report. Eligible treated and untreated

participants were matched on the propensity score for baseline

characteristics and AD pathology. Mixed models with estimated marginal

means were applied to assess the effect of treatment on trajectories of

symptoms in the presence or absence of AD pathology. Sex effects were

additionally analyzed.

RESULTS: Of the full Data Set, 427 participants met eligibility criteria of which 212

with a total of 840 data points were matched and included in the analyses.

After follow-up of up to 48 months, no significant differences in

symptomatic trajectories were observed between those with and without

AD pathology in both treated and untreated groups. The decline was more

pronounced in untreated male vs. female participants after 48 months.

Treated male participants performed better than untreated male

participants from the 24-month follow-up onward, a difference not

observed in female participants. These sex effects were independent of

the presence or absence of AD pathology. Sensitivity analyses confirmed

the robustness of the results.

 

CONCLUSION: This study does not confirm effects of acetylcholinesterase inhibitors or

memantine on the symptomatic course in individuals with the clinical

diagnosis of DAT, irrespective of underlying AD pathology. The observed

sex-specific treatment effects warrant further confirmatory studies.