Amyloid discordance analysis in cognitively normal monozygotic twins demonstrates that the memory domain is affected first in preclinical AD

Abstract Background The earliest cognitive changes in Alzheimer’s disease (AD), even before amyloid‐beta (Aβ) is abnormal, remain largely unclear. We recently observed a cohort of cognitively normal older monozygotic twins that 15% twin‐pairs were discordant for Aβ status (Fig. 1). In this cohort, we investigated early by comparing decline over 4 years among (one twin and co‐twin abnormal Aβ), with both (concordant Aβ‐), Aβ+). expected the rate to depend on baseline least concordant Aβ‐ increasing from Aβ‐, Aβ+ twins. Method From EMIF‐AD PreclinAD study selected cognition at who had [ 18 F]flutemetamol PET scan one follow‐up available (n=188; 90 twin‐pairs) (Table defined group using visual read dynamic images. tested whether concordance was associated performance time two repeated measures memory, attention, executive function (EF) language domains linear mixed models adjusted age, sex, education genetic relatedness. Result At showed impaired all ( Fig. 2). Discordant lower memory scores compared (discordant Aβ+, p=0.02; p=0.04). Over time, found improved (p=0.002), did not change (p=0.15), while declined p=0.03; p=0.07). No significant other domains. Conclusion Our findings provide further support AD are domain subtle may already present amyloid pathology can be detected scan.