NEW research offers insights into medical factors linked to the absence of Alzheimer’s disease neuropathologic changes (ADNC) in individuals aged 90 and older. The findings, based on data from The 90+ Study, reveal associations between specific medical histories, medications, and the presence or absence of Alzheimer’s hallmark neuropathologic changes, including amyloid plaques and neurofibrillary tangles.
The study examined 267 participants, predominantly female (75%), with an average age of 98 years. Researchers identified notable patterns that may suggest protective effects against ADNC. For instance, conditions such as heart disease were inversely associated with neuritic plaques (adjusted odds ratio [aOR] = 0.46) and beta-amyloid plaques (aOR = 0.33). Similarly, the use of ACE inhibitors (aOR = 0.46) and beta-blockers (aOR = 0.51) was linked to reduced neuritic plaque presence. Intriguingly, cataracts (aOR = 0.26) and glaucoma (aOR = 0.29) also showed an inverse relationship with neuropathologic changes.
Genetic factors, such as the presence of the APOE-ε2 allele (aOR = 0.39), were associated with fewer neurofibrillary tangles, while the APOE-ε4 allele significantly increased the odds of amyloid plaque presence (aOR = 8.10). Other factors, including hypertension (aOR = 0.44), seizure history (aOR = 0.16), and vasodilator use (aOR = 0.36), were also linked to variations in neuropathologic findings.
These results, though not statistically robust enough to survive multiple comparison corrections, point to intriguing pathways for further exploration. Researchers suggest differential lipid metabolism may underlie some observed patterns. However, survival bias and potential type I errors highlight the need for cautious interpretation.
This study underscores the complexity of Alzheimer’s disease pathology and the importance of examining diverse factors to understand resilience in the oldest-old population. Healthcare professionals should consider these findings as a stepping stone for deeper investigation into protective factors against Alzheimer’s disease.
Reference: Lee S et al. Medical Histories Associated With Absence of Alzheimer Disease Neuropathologic Changes in the Oldest-Old. Neurology. 2025;104(4). [Article in press].
Anaya Malik | AMJ
