ArticleEuropean journal of nuclear medicine and molecular imaging2026
Hypoperfusion in early-phase amyloid PET as a predictor of cognitive decline in Alzheimer's disease.
Article in European journal of nuclear medicine and molecular imaging, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeDual-phase amyloid PET enables concurrent assessment of amyloid burden and cerebral perfusion, providing both molecular and functional information within a single visit. While amyloid PET is well validated diagnostically, the prognostic value of early-phase perfusion remains less explored. We aimed to determine whether perfusion in Alzheimer’s disease (AD)–relevant regions is associated with longitudinal cognitive trajectories.
methodsWe analyzed 218 participants from a memory-clinic cohort ranging from cognitively unimpaired (CU, n = 65) to mild cognitive impairment (MCI, n = 115) and dementia (n = 38). Based on visual read of late-phase amyloid PET, 123 participants were classified as amyloid-positive (Aβ+) and 93 as amyloid-negative (Aβ–). The groups differed significantly in age, education, and baseline MMSE (all p < 0.01), but not in sex distribution. Early-phase perfusion was quantified as standardized uptake value ratios (SUVr) within an AD meta–region of interest (posterior cingulate, angular, and temporal cortex) and analyzed using linear mixed-effects models adjusting for age, sex, education, APOE ε4 genotype, and white matter lesion burden.
resultsAmong Aβ+ participants, 11 were CU, 79 MCI, and 33 dementia; among Aβ– participants, 53 were CU, 35 MCI, and 5 dementia. Perfusion declined progressively across clinical stages (CU > MCI > dementia) and was positively correlated with baseline MMSE (r = 0.39, p < 0.001). In Aβ+ individuals, higher baseline perfusion predicted slower MMSE decline over time (interaction β = 5.85, p < 0.001), whereas no such association was observed in the Aβ– group. No significant association was observed in amyloid-negative participants. These effects remained significant after adjustment for vascular and genetic covariates and were independent of amyloid plaque burden.
conclusionPerfusion derived from early-phase amyloid PET in AD-related regions is a reliable marker of cognitive status and progression in individuals with confirmed amyloid pathology. These findings highlight the added value of dual-phase PET as a practical, single-visit approach for combined diagnostic and prognostic evaluation, particularly where additional functional imaging is not feasible.
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