What Determines Cognitive Functioning in the Oldest-Old? The EMIF-AD 90+ Study

Abstract

Objectives Determinants of cognitive functioning in individuals aged 90 years and older, the oldest-old, remain poorly understood. We aimed to establish the association of risk factors, white matter hyperintensities (WMH), hippocampal atrophy and amyloid aggregation with cognition in the oldest-old. Methods We included 84 individuals without cognitive impairment and 38 individuals with cognitive impairment from the EMIF-AD 90+ Study (mean age 92.4 years) and tested cross-sectional associations between risk factors (cognitive activity, physical parameters, nutritional status, inflammatory markers and cardiovascular risk factors), brain pathology biomarkers (WMH and hippocampal volume on MRI, and amyloid binding measured with PET) and cognition. Additionally, we tested whether the brain pathology biomarkers were independently associated with cognition. When applicable, we tested whether the effect of risk factors on cognition was mediated by brain pathology. Results Lower values for handgrip strength, Short Physical Performance Battery (SPPB), nutritional status, HbA1c and hippocampal volume, and higher values for WMH volume and amyloid binding were associated with worse cognition. Higher past cognitive activity and lower BMI were associated with increased amyloid binding, lower muscle mass with more WMH, and lower SPPB scores with more WMH and hippocampal atrophy. The brain pathology markers were independently associated with cognition. The association of SPPB with cognition was partially mediated by hippocampal volume. Discussion In the oldest-old, physical parameters, nutritional status, HbA1c, WMH, hippocampal atrophy and amyloid binding are associated with cognitive impairment. Physical performance may affect cognition through hippocampal atrophy. This study highlights the importance to consider multiple factors when assessing cognition in the oldest-old.

Bridging Patterns of Neurocognitive Aging Across the Older Adult Lifespan

“…Slower rates of memory decline have also been associated with larger baseline whole brain volume across the older adult lifespan (Carmichael et al, 2012). Cross-sectional studies similarly report that oldest-old adults with larger hippocampus volumes have better episodic memory performance (Eguchi et al, 2019) and faster processing speeds (Legdeur et al, 2020;Pelkmans et al, 2021), comparable to what has been reported in younger-old adults (Carr et al, 2017;Gorbach et al, 2017;O'Shea et al, 2016).…”

What have we learned from cognition in the oldest-old

“…Although the importance of some risk factors for dementia appears to decline with increasing age, other risk factors have drawn attention in the oldest-old. Lower physical strength and performance, less participation in cognitive stimulating activities, and lower kidney function have been associated with cognitive impairment in the oldest-old [ 17 ▪ , 18 ▪ , 19 ]. Although it is difficult to disentangle cause and effect in these relationships, preserving physical health seems to be of utmost importance to preserve cognitive health in the oldest-old [ 20 ].…”

“…A recent review of neuroimaging findings in the oldest-old (Woodworth D, Scambray K, Corrada MM, Kawas CH, Sajjadi AS, manuscript under review) noted a lack of imaging studies in this age group. In general, studies found greater global, medial temporal, or hippocampal atrophy to be related to dementia risk [ 35 ], cognitive performance [ 18 ▪ , 36 ▪▪ , 37 ▪▪ ] and faster rates of cognitive decline [ 37 ▪▪ , 38 ▪ ]. High burden of white matter lesions was also a common finding and was associated with worse baseline scores and faster decline in measures of global cognition [ 18 ▪ , 37 ▪▪ ].…”

“…In general, studies found greater global, medial temporal, or hippocampal atrophy to be related to dementia risk [ 35 ], cognitive performance [ 18 ▪ , 36 ▪▪ , 37 ▪▪ ] and faster rates of cognitive decline [ 37 ▪▪ , 38 ▪ ]. High burden of white matter lesions was also a common finding and was associated with worse baseline scores and faster decline in measures of global cognition [ 18 ▪ , 37 ▪▪ ]. Amyloid burden assessed through PET, is usually high in the oldest-old and associated with dementia risk [ 35 ], worse cognitive performance [ 18 ▪ , 38 ▪ ], and faster cognitive decline [ 38 ▪ , 39 ].…”

“…High burden of white matter lesions was also a common finding and was associated with worse baseline scores and faster decline in measures of global cognition [ 18 ▪ , 37 ▪▪ ]. Amyloid burden assessed through PET, is usually high in the oldest-old and associated with dementia risk [ 35 ], worse cognitive performance [ 18 ▪ , 38 ▪ ], and faster cognitive decline [ 38 ▪ , 39 ]. However, many oldest-old can maintain normal cognition in the presence of a high amyloid burden [ 35 , 40 ].…”