White matter hyperintensities (WMHs) of presumed vascular origin are a frequent finding in cerebral magnetic resonance imaging of older people. They are attributed to small vessel disease and involved in the pathogenesis of cognitive decline. Since vascular risk factors, especially arterial hypertension, predispose to small vessel disease, we analyzed the association of systolic blood pressure (SBP), diastolic blood pressure (DBP), and antihypertensive medications with WMH volume in 560 participants of the 1000BRAINS study, drawn from the population-based Heinz Nixdorf Recall study (65.2±7.5 years; 51.4% men). Further, we analyzed treatment efficacy using a classification of 6 BP treatment groups defined by antihypertensive medication and level of BP: (1) untreated BP <120/<80 mm Hg, (2) untreated SBP 120 to 139 or DBP 80 to 89 mm Hg, (3) untreated BP ≥140 or ≥90 mm Hg, (4) treated BP <120/<80 mm Hg, (5) treated SBP 120 to 139 or DBP 80 to 89 mm Hg, and (6) treated BP ≥140 or ≥90 mm Hg. Median WMH volume (Q1–Q3) was 4.6 (3.0–7.8) cm 3 ; mean±SD of SBP and DBP was 128.6±17.4 and 76.1±9.8 mm Hg. In multivariable linear regression models, continuous SBP (β=0.63 cm 3 per 10 mm Hg [95% CI, 0.32–0.94]), DBP (0.64 cm 3 per 5 mmHg [95% CI, 0.37–0.91]), and antihypertensive treatment (1.23 cm 3 [95% CI, 0.14–2.23]) were significantly associated with WMH volume. Regarding treatment efficacy, only participants with hypertension despite treatment (treated BP ≥140 or ≥90 mm Hg) had significantly increased WMH volume (4.24 cm 3 [2.36–6.13]) compared with normotension without treatment (untreated BP <120/<80 mm Hg). Our results suggest that WMHs represent a marker of advanced hypertension pathology. Hence, early treatment should prevent WMHs.

In the normal aging process, the functional connectome restructures and shows a shift from more segregated to more integrated brain networks, which manifests itself in highly different cognitive performances in older adults. Underpinnings of this reorganization are not fully understood, but may be related to age-related differences in structural connectivity, the underlying scaffold for information exchange between regions. The structure-function relationship might be a promising factor to understand the neurobiological sources of interindividual cognitive variability, but remain unclear in older adults. Here, we used diffusion weighted and resting-state functional magnetic resonance imaging as well as cognitive performance data of 573 older subjects from the 1000BRAINS cohort (55-85 years, 287 males) and performed a partial least square regression on 400 regional functional and structural connectivity (FC and SC, respectively) estimates comprising seven resting-state networks. Our aim was to identify FC and SC patterns that are, together with cognitive performance, characteristic of the older adults aging process. Results revealed three different aging profiles prevalent in older adults. FC was found to behave differently depending on the severity of age-related SC deteriorations. A functionally highly interconnected system is associated with a structural connectome that shows only minor age-related decreases. Because this connectivity profile was associated with the most severe age-related cognitive decline, a more interconnected FC system in older adults points to a process of dedifferentiation. Thus, functional network integration appears to increase primarily when SC begins to decline, but this does not appear to mitigate the decline in cognitive performance.

Objectives: White matter hyperintensities (WMH) of presumed vascular origin are frequent in cerebral MRI of older people. They represent a sign of small vessel disease, are promoted by arterial hypertension, and relate to cognitive deficits. The interdependence of blood pressure and its treatment, WMH, and cognitive performance has not systematically been studied in population-based studies.Methods: Consequently, we analysed the interdependence of SBP, DBP, and antihypertensive medications, as well as BP/treatment category, with WMH and cognitive performance in 560 participants of the population-based 1000BRAINS study.Results: BP, its treatment, and BP/treatment category were moderately associated with cognitive performance (e. g. unadjusted b ¼ À0.10, 95%CI ¼ À0.19 to À0.02 for the association of SBP (per standard deviation of 17.2 mmHg) with global cognition (per standard deviation of 0.5 z score)]. The harmful effect of BP on cognition was strongly mediated by periventricular hyperintensities (PVH), which were significantly associated with both SBP [b ¼ 0.24, 95% CI ¼ 0.14-0.34 (per 1-point-increase in Fazekas score)] and global cognition (b ¼ À0.22, 95%CI ¼ À0.32 to À0.13). Thus, PVH mediated as much as 52% of the effects of SBP on cognitive performance. Mediation was less strong for deep white matter hyperintensities (DWMH, 16%), which showed less association with SBP (b ¼ 0.14, 95% CI ¼ 0.05-0.24) and global cognition (b ¼ À0.12, 95% CI ¼ À0.21 to À0.03). Regarding different cognitive domains, PVH most strongly mediated effects of SBP on nonverbal memory (94%) and executive function (81%). Conclusion:Our results indicate that PVH may predispose to cognitive impairment associated with hypertension, especially in the domains of nonverbal memory and executive function.