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TOPLINE:

A longitudinal cohort study showed that a higher amyloid-beta (Aβ) load in centenarians was associated with poorer cognitive performance, particularly executive functioning. Two thirds of centenarians maintained high cognitive performance with no or low Aβ loads, and five resilient individuals showed higher cognitive performance despite having high Aβ loads but low levels of tau pathology.

METHODOLOGY:

• This longitudinal cohort study used cross-sectional data on antemortem cognitive performance and postmortem neuropathology of 95 centenarians (median age at death, 103.5 years; 75% women) from the Dutch 100-plus Study and 38 patients (median age at death, 84 years) with Alzheimer's disease (AD) from the Netherlands Brain Bank.
• Participants underwent assessments through neuropsychological tests evaluating memory, fluency, attention or processing speed, and executive functioning, along with measures of global cognition performed a median of 10 months before brain donation.
• Neuropathologic evaluation included the detection of quantitative Aβ loads in four neocortical, five hippocampal, and three parahippocampal regions.
• Centenarians were classified on the basis of the minimum observed Aβ load in the frontal cortex (the most affected region) of patients with AD, as well as cerebral amyloid angiopathy (CAA) stage and type.

TAKEAWAY:

• The centenarians were categorised according to their Aβ loads: none (9%), low (56%), and high (35%).
• Participants with no or low Aβ loads had better executive function and global cognition than those with high Aβ loads in the frontal cortex, as well as other neocortical and hippocampal regions.
• Even after adjusting for copathologies, higher Aβ loads in neocortical regions, higher CAA stages, and the presence of CAA type 1 were associated with lower cognitive performance.
• Five centenarians were classified as resilient (having high Aβ loads and cognitive scores in the top 25%) and had a significantly lower levels of tau pathology.

IN PRACTICE:

"Accumulation of Aβ pathology should not be considered a benign consequence of aging," the authors wrote. "These findings support the amyloid-cascade hypothesis and suggest that therapies aimed at reducing Aβ may be of relevance for the older population," they concluded.

SOURCE:

This study was led by Susan K. Rohde, MSc, and Maruelle C. Luimes, MSc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. It was published online on June 30 in JAMA Neurology.

LIMITATIONS:

The 6F/3D antibody was used to visualise Aβ pathology instead of the recommended 4G8 antibody. The analysis did not differentiate between specific Aβ isoforms, plaque maturation, or different types of Aβ depositions, which may differentially affect cognitive performance. Furthermore, this study was limited by the collinearity among Aβ loads and loads of copathologies, rather than staging, and a possibility of additional bias due to the use of multiple imputations.

DISCLOSURES:

This study was supported by BrightFocus, VUmc Foundation, and Surf Sara. Several authors reported having financial and other ties with various organisations. Details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.