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As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7 mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P  < 0.001; MD [10 −3  mm 2 /s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P  < 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

Importance: As SARS-CoV-2 infections have been shown to affect the central nervous system, it is crucial to investigate associated alterations of brain structure and neuropsychological sequelae to help address future health care needs. Objective: To determine whether a mild to moderate SARS-CoV-2 infection is associated with alteration of brain structure detected by magnetic resonance imaging (MRI) and neuropsychological deficits. Design, Setting and Participants: Following a case-control design, 223 non-vaccinated individuals with a positive polymerase chain reaction test (PCR) for SARS-CoV-2 obtained between 1 March and 31 December 2020 received MRI and neuropsychological assessments within the framework of the Hamburg City Health Study (median 9.7 months after testing). Two hundred twenty-three healthy controls, examined prior to the SARS-CoV-2 pandemic, were drawn from the main study and matched for age, sex, education and cardiovascular risk factors. Exposure: Infection with SARS-CoV-2 confirmed by a positive PCR. Main Outcomes and Measures: Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load and neuropsychological test scores. Results: The present analysis included 223 individuals recovered from mainly mild to moderate SARS-CoV-2 infections (100 female/123 male, age [years], mean +- SD, 55.54 +- 7.07) and 223 matched healthy controls (93 female/130 male, 55.74 +- 6.60). Among all 11 MR imaging markers tested, significant differences between groups were found in global measures of mean diffusivity and extracellular free-water which were both elevated in the white matter of post-SARS-CoV-2 individuals comparing to matched controls (free-water: 0.148 +- 0.018 vs. 0.142 +- 0.017, P<.001; mean diffusivity [10-3 mm2/s]: 0.747 +- 0.021 vs. 0.740 +- 0.020, P<.001). Classification accuracy for detecting post-SARS-CoV-2 individuals based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Conclusions and Relevance: Our findings suggest that subtle changes in white matter extracellular water content may last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

AimThe aim of the PAROBRAIN study was to examine the association of periodontal health with microstructural white matter integrity and cerebral small vessel disease (CSVD) in the Hamburg City Health Study, a large population‐based cohort with dental examination and brain magnetic resonance imaging (MRI).Materials and MethodsPeriodontal health was determined by measuring clinical attachment loss (CAL) and plaque index. Additionally, the decayed/missing/filled teeth (DMFT) index was quantified. 3D‐FLAIR and 3D‐T1‐weighted images were used for white matter hyperintensity (WMH) segmentation. Diffusion‐weighted MRI was used to quantify peak width of skeletonized mean diffusivity (PSMD).ResultsData from 2030 participants were included in the analysis. Median age was 65 years, with 43% female participants. After adjusting for age and sex, an increase in WMH load was significantly associated with more CAL, higher plaque index and higher DMFT index. PSMD was significantly associated with the plaque index and DMFT. Additional adjustment for education and cardiovascular risk factors revealed a significant association of PSMD with plaque index (p < .001) and DMFT (p < .01), whereas effects of WMH load were attenuated (p > .05).ConclusionsThese findings suggest an adverse effect of periodontal health on CSVD and white matter integrity. Further research is necessary to examine whether early treatment of periodontal disease can prevent microstructural brain damage.