Potentially modifiable factors explaining monozygotic twin discordance in amyloid pathology

Abstract

AbstractBackgroundThe heritability of global amyloid burden in older adults was previously found to be moderate (41%), suggesting environmental factors to play an important role in early Alzheimer’s disease (AD) pathology. Identifying these factors may aid in the development of successful prevention strategies. Several, potentially modifiable, risk factors for dementia have been previously reported by Livingston and colleagues (Lancet, 2020). We here aim to identify which of these risk factors explain observed twin discordance in amyloid pathology in a sample of cognitively unimpaired monozygotic twin‐pairs.MethodsWe included 31 initially cognitively unimpaired twin‐pairs aged>60 years from the EMIF‐AD PreclinAD study who were discordant on amyloid status (defined by visual read of dynamic [18F]flutemetamol‐PET images). Paired samples t‐tests (continuous measures) and McNemar’s tests (dichotomous measures) were applied to investigate which factors associated with twin discordance. Selected risk factors included comorbid diseases, lifestyle and vascular risk factors (see table 2).ResultsTwins were on average 72.7±7.0 years old, consisted of 48% females, and 58% Apoe‐ε4 carriers (table 1). Twins with a positive amyloid status showed lower body mass index (BMI) and glucose levels compared to their amyloid negative co‐twin (table 2, figure 1A&B). We also observed a trend towards lower diastolic blood pressure in amyloid positive twins (table 2). In accordance with inclusion criteria for the study we observed very low prevalence of comorbid disorders in both groups. Further, no group differences were observed in lifestyle factors, such as smoking, alcohol use, physical activity and sleep quality.ConclusionsIn a sample of monozygotic twin‐pairs discordant for amyloid pathology, we found lower BMI and glucose levels to be associated with the presence of amyloid pathology. Although Livingston and colleagues reported high BMI (obesity) at mid‐life (age 45‐65) to increase the risk for dementia, effects of BMI have previously been found to differ in mid‐ and late‐age populations. In line with our results, lower BMI at later life (>65 years) has previously been found to increase AD‐risk. For the development of prevention strategies, it would be of relevance to further investigate these dynamic age‐related effects.