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Amyloid discordance analysis in cognitively normal monozygotic twins demonstrates that the memory domain is affected first in preclinical AD
Author(s) -
Tomassen Jori,
den Braber Anouk,
Van Berckel Bart N.M.,
Yaqub Maqsood,
Boomsma Dorret I,
Scheltens Philip,
Tijms Betty M.,
Visser Pieter Jelle
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.055178
Subject(s) - concordance , twin study , monozygotic twin , cognition , cohort , psychology , cognitive test , cognitive decline , dementia , developmental psychology , medicine , audiology , disease , psychiatry , heritability , biology , genetics
Background The earliest cognitive changes in Alzheimer’s disease (AD), even before amyloid‐beta (Aβ) is abnormal, remain largely unclear. We recently observed in a cohort of cognitively normal older monozygotic twins that 15% of twin‐pairs were discordant for Aβ status (Fig. 1). In this cohort, we investigated early cognitive changes by comparing cognitive decline over 4 years among twin‐pairs discordant for Aβ status (one twin normal Aβ and co‐twin abnormal Aβ), twin‐pairs with both normal Aβ (concordant Aβ‐), and twin‐pairs with both abnormal Aβ (concordant Aβ+). We expected the rate of cognitive decline to depend on baseline Aβ status with the least decline in concordant Aβ‐ twins and increasing decline from discordant Aβ‐, discordant Aβ+ to concordant Aβ+ twins. Method From the EMIF‐AD PreclinAD study we selected monozygotic twins with normal cognition at baseline who had a [ 18 F]flutemetamol PET scan and at least one cognitive follow‐up available (n=188; 90 twin‐pairs) (Table 1). We defined Aβ group status using visual read of dynamic [ 18 F]flutemetamol PET images. We tested whether twin Aβ concordance status at baseline was associated with cognitive performance at baseline and over 4 years time with two repeated measures in memory, attention, executive function (EF) and language domains using linear mixed models adjusted for age, sex, education and genetic relatedness. Result At baseline concordant Aβ+ twins showed impaired performance in all domains ( Fig. 2). Discordant Aβ+ and concordant Aβ+ twins showed lower memory scores compared to concordant Aβ‐ twins (discordant Aβ+, p=0.02; concordant Aβ+, p=0.04). Over time, we found that for concordant Aβ‐ twins memory improved over time (p=0.002), discordant Aβ‐ twins did not change over time (p=0.15), while discordant Aβ+ and concordant Aβ+ twins declined on memory (concordant Aβ+, p=0.03; discordant Aβ+, p=0.07). No significant changes over time were observed in the other domains. Conclusion Our findings provide further support that the earliest cognitive changes in AD are found in the memory domain and that subtle memory changes may already by present before amyloid pathology can be detected on a PET scan.