Associations between white matter hyperintensities, lacunes, entorhinal cortex thickness, declarative memory and leisure activity in cognitively healthy older adults: A 7-year study.

INTRODUCTION: Cerebral small vessel disease (cSVD) is a growing epidemic that affects brain health and cognition. Therefore, a more profound understanding of the interplay between cSVD, brain atrophy, and cognition in healthy aging is of great importance. In this study, we examined the association between white matter hyperintensities (WMH) volume, number of lacunes, entorhinal cortex (EC) thickness, and declarative memory in cognitively healthy older adults over a seven-year period, controlling for possible confounding factors. Because there is no cure for cSVD to date, the neuroprotective potential of an active lifestyle has been suggested. Supporting evidence, however, is scarce. Therefore, a second objective of this study is to examine the relationship between leisure activities, cSVD, EC thickness, and declarative memory. METHODS: We used a longitudinal dataset, which consisted of five measurement time points of structural MRI and psychometric cognitive ability and survey data, collected from a sample of healthy older adults (baseline N = 231, age range: 64-87 years, age M = 70.8 years), to investigate associations between cSVD MRI markers, EC thickness and verbal and figural memory performance. Further, we computed physical, social, and cognitive leisure activity scores from survey-based assessments and examined their associations with brain structure and declarative memory. To provide more accurate estimates of the trajectories and cross-domain correlations, we applied latent growth curve models controlling for potential confounders. RESULTS: Less age-related thinning of the right (ß = 0.92, p<.05) and left EC (ß = 0.82, p<.05) was related to less declarative memory decline; and a thicker EC at baseline predicted less declarative memory loss (ß = 0.54, p<.05). Higher baseline levels of physical (ß = 0.24, p<.05), and social leisure activity (ß = 0.27, p<.01) predicted less thinning of right EC. No relation was found between WMH or lacunes and declarative memory or between leisure activity and declarative memory. Higher education was initially related to more physical activity (ß = 0.16, p<.05) and better declarative memory (ß = 0.23, p<.001), which, however, declined steeper in participants with higher education (ß = -.35, p<.05). Obese participants were less physically (ß = -.18, p<.01) and socially active (ß = -.13, p<.05) and had thinner left EC (ß = -.14, p<.05) at baseline. Antihypertensive medication use (ß = -.26, p<.05), and light-to-moderate alcohol consumption (ß = -.40, p<.001) were associated with a smaller increase in the number of lacunes whereas a larger increase in the number of lacunes was observed in current smokers (ß = 0.30, p<.05). CONCLUSIONS: Our results suggest complex relationships between cSVD MRI markers (total WMH, number of lacunes, right and left EC thickness), declarative memory, and confounding factors such as antihypertensive medication, obesity, and leisure activitiy. Thus, leisure activities and having good cognitive reserve counteracting this neurodegeneration. Several confounding factors seem to contribute to the extent or progression/decline of cSVD, which needs further investigation in the future. Since there is still no cure for cSVD, modifiable confounding factors should be studied more intensively in the future to maintain or promote brain health and thus cognitive abilities in older adults.

Performance of three freely available methods for extracting white matter hyperintensities: FreeSurfer, UBO Detector, and BIANCA.

White matter hyperintensities (WMH) of presumed vascular origin are frequently found in MRIs of healthy older adults. WMH are also associated with aging and cognitive decline. Here, we compared and validated three algorithms for WMH extraction: FreeSurfer (T1w), UBO Detector (T1w + FLAIR), and FSL's Brain Intensity AbNormality Classification Algorithm (BIANCA; T1w + FLAIR) using a longitudinal dataset comprising MRI data of cognitively healthy older adults (baseline N = 231, age range 64-87 years). As reference we manually segmented WMH in T1w, three-dimensional (3D) FLAIR, and two-dimensional (2D) FLAIR images which were used to assess the segmentation accuracy of the different automated algorithms. Further, we assessed the relationships of WMH volumes provided by the algorithms with Fazekas scores and age. FreeSurfer underestimated the WMH volumes and scored worst in Dice Similarity Coefficient (DSC = 0.434) but its WMH volumes strongly correlated with the Fazekas scores (rs  = 0.73). BIANCA accomplished the highest DSC (0.602) in 3D FLAIR images. However, the relations with the Fazekas scores were only moderate, especially in the 2D FLAIR images (rs  = 0.41), and many outlier WMH volumes were detected when exploring within-person trajectories (2D FLAIR: ~30%). UBO Detector performed similarly to BIANCA in DSC with both modalities and reached the best DSC in 2D FLAIR (0.531) without requiring a tailored training dataset. In addition, it achieved very high associations with the Fazekas scores (2D FLAIR: rs  = 0.80). In summary, our results emphasize the importance of carefully contemplating the choice of the WMH segmentation algorithm and MR-modality.

Associations of subclinical cerebral small vessel disease and processing speed in non-demented subjects: A 7-year study.

Markers of cerebral small vessel disease (CSVD) have previously been associated with age-related cognitive decline. Using longitudinal data of cognitively healthy, older adults (N = 216, mean age at baseline = 70.9 years), we investigated baseline status and change in white matter hyperintensities (WMH) (total, periventricular, deep), normal appearing white matter (NAWM), brain parenchyma volume (BPV) and processing speed over seven years as well as the impact of different covariates by applying latent growth curve (LGC) models. Generally, we revealed a complex pattern of associations between the different CSVD markers. More specifically, we observed that changes of deep WMH (dWMH), as compared to periventricular WMH (pWMH), were more strongly related to the changes of other CSVD markers and also to baseline processing speed performance. Further, the number of lacunes rather than their volume reflected the severity of CSVD. With respect to the studied covariates, we revealed that higher education had a protective effect on subsequent total WMH, pWMH, lacunar number, NAWM volume, and processing speed performance. The indication of antihypertensive drugs was associated with lower lacunar number and volume at baseline and the indication of antihypercholesterolemic drugs came along with higher processing speed performance at baseline. In summary, our results confirm previous findings, and extend them by providing information on true within-person changes, relationships between the different CSVD markers and brain-behavior associations. The moderate to strong associations between changes of the different CSVD markers indicate a common pathological relationship and, thus, support multidimensional treatment strategies.