CROSS-SECTIONAL TRAJECTORIES OF NEURODEGENERATION, COGNITIVE AND PHYSICAL MARKERS IN COGNITIVELY NORMAL SUBJECTS AGED 60-100 YEARS

Abstract

Ageing is related to neurodegeneration and decrease in cognitive functioning and physical performance. However, the trajectories of these changes during ageing are still unclear. The aim of this study is to explore the cross-sectional trajectories of neurodegeneration, cognitive functioning and physical performance in a cognitively normal population. We selected 210 subjects aged 60 years and older from the PreclinAD study and 22 subjects from the 90+ Study at the VU Medical Center. All subjects were cognitively normal (Clinical Dementia Rating = 0). Neurodegeneration markers were hippocampal volume on MRI and amyloid binding potential measured with positron emission tomography. Cognitive markers were MMSE, Digit Symbol Substitution Test, CERAD memory test and letter fluency. Markers of physical performance were grip strength and skeletal muscle mass (SMM). All measurements were Z transformed, with negative scores representing worse outcome, using subjects aged 60–65 years as reference group. Non-parametric local spline regression analysis (LOESS) was performed to determine trajectories of changes in each marker over age. Critical age was defined as the age at which the z-score of the ageing marker was significantly lower than that of the 60–65 year old reference group. Subjects had a mean age of 73.1 years (SD=10.1). Critical ages were between 65 and 70 years old, with the exception of letter fluency, which had a critical age of 78 years. The trajectories after the critical age differed between markers. Hippocampal volume showed the steepest decline compared to the reference group whereas amyloid load and SMM plateaued after the age of 85 years. In this cross-sectional study, neurodegeneration, cognitive and physical markers show specific trajectories with ageing. The stabilization of amyloid load and SMM at high age might be due to selection bias towards very old subjects who are resilient towards decline on these measures or who had a higher starting point. The observation that cognitive functioning continued to decline while amyloid load stabilized at high age, may suggest that amyloid pathology is a less important cause for cognitive decline at older ages. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement no. 115372. Cross-sectional trajectories of neurodegeneration, cognitive and physical markers.