The impact of diabetes on cognitive aging and dementia

The impact of prediabetes and diabetes on different stages of cognitive function during aging remains unclear. This thesis aimed to investigate the impact of prediabetes and of diabetes on cognitive aging—from cognitive deficits, through cognitive decline, to dementia—, explore underlying cerebral mechanisms and identify factors that may protect older adults with diabetes from dementia. The four studies in this thesis were based on data from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), the SNAC-K brain magnetic resonance imaging (MRI) study, and the Swedish Adoption/Twin Study of Aging (SATSA).

Study I. This study used SNAC-K data to identify the cognitive domains sensitive to the detrimental impact of diabetes. In cognitively intact older adults, diabetes was associated with lower performance in perceptual speed (β -1.10; 95% CI -1.98, -0.23), category fluency (β -1.27; 95% CI -2.52, -0.03), and digit span forward (β -0.35; 95% CI -0.54, -0.17). These results suggest that domains of fluid abilities are more sensitive to diabetes than are other cognitive domains.

Study II. This study used 23 years of follow-up data from SATSA to investigate the effect of prediabetes and of diabetes on trajectories of cognitive decline in different domains. Diabetes accelerated cognitive decline in perceptual speed (β -0.25; 95% CI -0.44, -0.05) and verbal abilities (β -0.19; 95% CI -0.33, -0.04). Prediabetes was associated with poor memory performance at baseline but with a less steep memory decline over time.

Study III. The relationship of prediabetes and of diabetes with global cognitive decline and structural brain changes was assessed with data from SNAC-K and the SNAC-K MRI study. Both accelerated global cognitive decline. Prediabetes was associated with smaller global brain volume, particularly smaller white matter volume at baseline, and diabetes with accumulation of white matter hyperintensities (β 0.56, 95% CI 0.07–1.05) over time.

Study IV. The compensatory effect of an active and socially integrated lifestyle on dementia risk in older adults with diabetes was examined with data from SNAC-K. Participants with diabetes and an inactive lifestyle had a higher risk of dementia (HR 6.0, 95% CI 3.0–12.3) than diabetes-free participants with an active lifestyle (high engagement in leisure activities or/and rich social network). In participants with diabetes, an active lifestyle was associated with less of a raised risk (HR 1.9, 95% CI 1.1–3.4).

Conclusions. In the initial phase of cognitive deterioration, the domains primarily affected by diabetes may be processing speed, executive function, and attention/primary memory. Over time, having either prediabetes or diabetes accelerates the decline in fluid abilities (i.e., perceptual speed and verbal abilities) and global cognitive decline. At the structural brain level, diabetes is associated with the accumulation of cerebral microvascular lesions, which might start already during prediabetes. Finally, diabetes is associated with an increased risk of dementia. However, an active and socially integrated lifestyle may significantly counteract the detrimental effect of diabetes on brain aging.

List of scientific papers

I. Marseglia A, Fratiglioni L, Laukka EJ, Santoni G, Pedersen NL, Bäckman L, Xu W. Early cognitive deficits in type 2 diabetes: a population-based study. J Alzheimers Dis. 2016;53:1069-1078.
https://doi.org/10.3233/JAD-160266

II. Marseglia A, Dahl Aslan AK, Fratiglioni L, Santoni G, Pedersen NL, Xu W. Cognitive trajectories in prediabetes and diabetes: a population-based cohort study. J Gerontol A Biol Sci Med Sci. 2018;73:400-406.
https://doi.org/10.1093/gerona/glx112

III. Marseglia A, Fratiglioni L, Kalpouzos G, Wang R, Bäckman L, Xu W. Prediabetes and diabetes accelerate cognitive decline and predict microvascular lesions: a population-based longitudinal study. [Submitted]

IV. Marseglia A, Wang HX, Rizzuto D, Fratiglioni L, Xu W. An active lifestyle and a rich social network counteract the risk of dementia related to diabetes: a population-based cohort study. [Submitted]