Small Vessel Disease, Amyloid Pathology Can Independently Reduce Cognition in Adults With T2D

Small vessel disease (SVD) and amyloid positivity can independently worsen cognitive functioning in non-demented older adults with type 2 diabetes (T2D), according to investigators who conducted a cross-sectional study and published findings in Scientific Reports. However, amyloid pathology was not associated with cognitive decline after adjusting for SVD, which suggests that diabetes pathology is not the only factor that contributes to cognitive decline in this patient population.

Diabetes is a known risk factor for cognitive decline and dementia, in part because it negatively affects insulin signaling and promotes hyperglycemia, advanced glycation, chronic low-grade inflammation, SVD, and large vessel disease.

It is also a risk factor for dementia because it promotes Alzheimer disease (AD) pathology. This pathology can be measured using brain imaging— white matter hyperintensities (WMH) measure SVD, total gray matter (GM) thickness/volume is a measure of atrophy, and quantified amyloid-beta (Aβ) load measures amyloid plaque buildup.

While there is no concrete evidence which demonstrates a clear link between diabetes and AD, previous investigators have observed a link between amyloid pathology and SVD and cognitive decline in patients with T2D. In the current cross-sectional study, investigators evaluated the relationship between SVD and amyloid burden on cognitive functioning in non-demented older adults with T2D.

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Investigators evaluated the brain imaging of 47 patients with non-demented T2D who participated in the T2D Israel Diabetes and Cognitive Decline Study (average age 78 years, 64% females). They calculated WMH, GM volume, and (Aβ) load (via amyloid-PET).

Amyloid positivity and WMH volume (measures SVD) were associated with worse global cognitive functioning, upon adjusting scores for sociodemographic factors, T2D characteristics, and GM volume.

“Our findings are in line with previous studies demonstrating an association between higher amyloid and cognitive impairment,” wrote study authors. “This complex relationship between amyloid deposition and cognitive functioning may depend on the specific cohort characteristics and disease stage.”

T2D is associated with SVD, and more severe SVD has been associated with reduced cognition in patients with diabetes. Although current findings reflect this literature, they do support a concrete relationship between diabetes and amyloid positivity.

Only 23% of the cohort had amyloid positivity, which is relatively lower than accepted rates for people of this age. According to the study authors, this suggests that T2D is associated with a lower rate of amyloid pathology, although it is still independently associated with cognitivedecline.

The study authors note there are limitations to this study, which include study design, small patient population, small number of patients with high Aβ load measures, possible selection bias, longer duration between brain scans, and inability to generalize findings for patients without diabetes.

“Our findings suggest that multiple factors may independently contribute to cognitive decline in non-demented older adults with type-2 diabetes, indicating a multimodal and individualized approach for the prevention, diagnosis, and treatment of cognitive decline in this population,” study authors wrote.

REFERENCE

Lesman-Segev OH, Shekhtman SG, Springer RR, et al. Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes. Sci Rep. 2024;14:2741. doi:10.1038/s41598-024-53043-x