Cumulative Frailty in Late‐Middle Aged Men is Associated with Later Regional Abnormal White Matter and Decreased Processing Speed

Abstract

AbstractBackgroundFrailty refers to a person’s physical and functional capabilities and increases during aging. Abnormal white matter (AWM; e.g., hyperintensities on T2‐weighted MRI) is a neuroimaging marker of small‐vessel vascular disease associated with increased risk of Alzheimer’s Disease and related dementias. While some studies have found associations between frailty indices (FIs) and global AWM, their association with accumulation of regional AWM and any related cognitive correlates is understudied.Method342 men from the Vietnam Era Twin Study of Aging with frailty measured at study baseline (mean age = 56.4) and structural MRI scans at follow‐up (mean 5.5 years later) were included (Table 1). The FI measure was based on a cumulative deficit model[1] using an index of 37 health‐ and function‐related items. Global AWM was defined using morphological operators on multi‐channel, three‐class tissue segmentation[2]. A novel watershed routine, applied to our AWM frequency atlas, generated 5 distinct AWM parcellations: frontal, posterior, anterior periventricular, deep, and temporal stem (Figure 1A). Cognitive factor scores (memory, processing speed, executive function, fluency) were derived from normative neuropsychological test performance.ResultMixed‐effects linear regression models controlling for age, years of education and twin‐pair demonstrated that higher baseline FI was associated with greater future AWM volume in temporal stem (p = 0.03) and anterior periventricular (p = 0.02) regions, but not for global or other parcellations (Figure 1B). Baseline FI was not cross‐sectionally associated with any cognitive factor score but was associated longitudinally with decreased processing speed (p = 0.002) (Table 2).ConclusionHigher cumulative frailty in late‐middle aged men was associated with greater future AWM burden and greater decline in processing speed. These findings suggest that cumulative frailty during the 6th decade is a relevant indicator and possible predictor of future pathological structural and functional processes in the brain. Longitudinal studies may elucidate whether frailty affects AWM progression and cognitive decline along a common causal pathway.