Juyoun Lee

Gray and white matter changes linking cerebral small vessel disease to gait disturbances

Objective: To investigate the topographic changes of white matter (WM) integrity and cortical thickness related to gait disturbances and determine whether these neural correlates mediate the association between cerebral small vessel disease (CSVD) and gait disturbances. Methods: A total of 129 patients with subcortical vascular cognitive impairment were included. CSVD severity was quantified as global and regional WM hyperintensities (WMH) volume and lacune and microbleed numbers. Amyloid burdens were assessed using Pittsburgh compound B (PiB)–PET scanning. Gait score was measured using a standardized scale. WM integrity was assessed by applying tract-based spatial statistics. Cortical thickness was measured using surface-based methods. Path analysis for gait score was performed using regional CSVD markers as predictors and fractional anisotropy (FA) and cortical thickness as mediators. Results: Periventricular WMH (PWMH) volume was associated with gait score, regardless of other CSVD. PiB retention ratio was not associated with gait score. Gait score was correlated with FA in the frontal and parietal WM and bilateral corpus callosum and with cortical thinning in the bilateral frontal and lateral temporo-parieto-occipital regions. Path analysis for gait score showed that PWMH contributed to gait disturbances with the mediation of mean FA or cortical thickness. Conclusions: Our findings suggest that WMH-related cortical thinning as well as disrupted integrity of periventricular WM is linked to gait disturbances.

Early- vs late-onset subcortical vascular cognitive impairment

Objective: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function. Methods: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset ≥65 years) groups. All patients underwent neuropsychological tests, 3T brain MRI, and [11C] Pittsburgh compound B (PiB)–PET. We compared pathologic burden such as small vessel disease and amyloid burden; structural changes such as structural network, cortical thickness, and hippocampal volume; and cognitive function between EO-SVCI and LO-SVCI. Results: EO-SVCI patients had more lacunes, while LO-SVCI patients had higher PiB standardized uptake value ratios. EO-SVCI patients exhibited more severe structural network disruptions in the frontal area, while LO-SVCI patients exhibited more severe cortical and hippocampal atrophy. Although disease severity did not differ between the 2 groups, frontal-executive dysfunction was more severe in EO-SVCI patients. Conclusions: EO-SVCI patients showed more vascular related factors, while LO-SVCI patients exhibited more Alzheimer disease–related characteristics. The greater number of lacunes in EO-SVCI might account for the more severe frontal network disruption and frontal-executive dysfunction, while the greater amyloid burden in LO-SVCI might account for the more severe cortical and hippocampal atrophy. Our findings suggest that the age at onset is a crucial factor that determines distinct features in SVCI patients, such as pathologic burden, structural changes, and cognitive function.

Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals.

We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1-weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was ≥17 mg/g for men and ≥25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures.

Combined effects of physical exercise and education on age-related cortical thinning in cognitively normal individuals

We investigated the association between self-reported physical exercise and cortical thickness in a large sample of cognitively normal individuals. We also determined whether a combination of physical exercise and education had more protective effects on age-related cortical thinning than either parameter alone. A total of 1,842 participants were included in this analysis. Physical exercise was assessed using a questionnaire regarding intensity, frequency, and duration. Cortical thickness was measured using a surface-based method. Longer duration of exercise (≥1 hr/day), but not intensity or frequency, was associated with increased mean cortical thickness globally (P-value = 0.013) and in the frontal regions (P-value = 0.007). In particular, the association of exercise with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, left postcentral, and inferior parietal regions. The combination of higher exercise level and higher education level showed greater global and frontal mean thickness than either parameter alone. Testing for a trend with the combination of high exercise level and high education level confirmed this finding (P-value = 0.001–0.003). Our findings suggest that combined exercise and education have important implications for brain health, especially considering the paucity of known protective factors for age-related cortical thinning.

18F-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy

Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau.