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The manifestation of cognitive and physical impairment in stroke patients before the acute event suggests accumulating subclinical vascular pathology in the brain. We investigated whether impairments in cognitive and physical functioning were associated with an increased stroke risk. Between 2002 and 2008, 8,519 stroke-free non-demented participants from the population-based Rotterdam Study underwent cognition and physical assessments including Mini-Mental State Examination, 15-word learning test, Stroop test, letter-digit substitution test, verbal fluency test, Purdue pegboard test and questionnaires on basic and instrumental activities of daily living (BADL; IADL). Principal component analysis was used to derive global cognition (G-factor). Incident stroke was assessed through continuous monitoring of medical records until 2016. Among 8,519 persons (mean age 66.0 years; 57.8% women), 489 suffered a stroke during mean follow-up of 8.7 years (SD: 2.9). Worse G-factor was associated with higher stroke risk (Hazard Ratio 1.21, 95% CI: 1.06–1.38), largely driven by unspecified stroke. Likewise, worse scores on 15-word learning test, Stroop test, Purdue pegboard test, IADL, and BADL were associated with higher risk of stroke. Thus both worse cognitive and physical functioning were associated with a higher stroke risk, in particular unspecified stroke and persons with worse memory, information processing, executive function, and motor function.

CVD risk prediction in diabetics is imperfect, as risk models are derived mainly from the general population. We investigate whether the addition of retinopathy and retinal vascular caliber improve CVD prediction beyond established risk factors in persons with diabetes. We recruited participants from the Singapore Malay Eye Study (SiMES, 2004–2006) and Singapore Prospective Study Program (SP2, 2004–2007), diagnosed with diabetes but no known history of CVD at baseline. Retinopathy and retinal vascular (arteriolar and venular) caliber measurements were added to risk prediction models derived from Cox regression model that included established CVD risk factors and serum biomarkers in SiMES, and validated this internally and externally in SP2. We found that the addition of retinal parameters improved discrimination compared to the addition of biochemical markers of estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hsCRP). This was even better when the retinal parameters and biomarkers were used in combination (C statistic 0.721 to 0.774, p = 0.013), showing improved discrimination, and overall reclassification (NRI = 17.0%, p = 0.004). External validation was consistent (C-statistics from 0.763 to 0.813, p = 0.045; NRI = 19.11%, p = 0.036). Our findings show that in persons with diabetes, retinopathy and retinal microvascular parameters add significant incremental value in reclassifying CVD risk, beyond established risk factors.

Evidences suggested that both corpus callosum (CC) degeneration and alternations of homotopic inter-hemispheric functional connectivity (FC) are present in Alzheimer’s disease (AD). However, the associations between region-specific CC degeneration and homotopic inter-hemispheric FC and their relationships with memory deficits in AD remain uncharacterized. We hypothesized that selective CC degeneration is associated with memory impairment in AD and amnestic mild cognitive impairment (aMCI), which is mediated by homotopic inter-hemispheric functional dysconnectivity. Using structural magnetic resonance imaging (MRI) and task-free functional MRI, we assessed the CC volume and inter-hemispheric FC in 66 healthy controls, 41 aMCI and 41 AD. As expected, AD had CC degeneration and attenuated inter-hemispheric homotopic FC. Nevertheless, aMCI had relatively less severe CC degeneration (mainly in mid-anterior, central, and mid-posterior) and no reduction in inter-hemispheric homotopic FC. The degeneration of each CC sub-region was associated with specific inter-hemispheric homotopic functional disconnections in AD and aMCI. More importantly, impairment of inter-hemispheric homotopic FC partially mediated the association between CC (particularly the central and posterior parts) degeneration and memory deficit. Notably, these results remained after controlling for hippocampal volume. Our findings shed light on how CC degeneration and the related inter-hemispheric FC impact memory impairment in early stage of AD.