Among 500 adults (mean age 67, 68% female) carrying both amyloid-beta and tau pathology confirmed by PET imaging, those who remained cognitively unimpaired — so-called Non-Demented Alzheimer's Neuropathology (NDAN) individuals — showed cerebral blood flow (CBF) comparable to amyloid-free controls. The most striking differences emerged in parietal and occipital cortices, where NDAN individuals maintained 22–34% higher CBF than cognitively impaired counterparts with identical pathological burden. White matter hyperintensity volume separated impaired from control groups but failed to distinguish NDAN individuals, suggesting CBF preservation is a more sensitive vascular marker of resilience.
This finding reframes a long-standing puzzle in Alzheimer's research: why do roughly 30% of people with full amyloid-tau pathology never develop dementia? The vascular hypothesis — that robust cerebral perfusion may buffer neuronal function against tau toxicity — gains meaningful support here. Notably, the largest CBF differences appeared in regions that accumulate amyloid early but remain largely tangle-free, implying perfusion may protect specifically against the downstream spread of tau pathology rather than amyloid deposition itself. For adults, this elevates interventions that improve cerebrovascular health — aerobic exercise, hypertension control, sleep optimization — as potential resilience strategies worth investigating in trials.
Important caveats apply: the retrospective design cannot establish causality, the NDAN cohort is small (n=38), and the sample skews White and highly educated, limiting generalizability. As a preprint posted on medRxiv and not yet peer-reviewed, these findings remain preliminary and should be interpreted cautiously. If replicated, this work could be paradigm-shifting for vascular-targeted prevention strategies.