We investigated the association between metabolic syndrome risk factors and brain tissue integrity, as assessed by magnetic resonance imaging.From the Leiden Longevity Study, which is a community-based study of long-lived subjects, their offspring, and partners thereof, 130 subjects (61 men; mean age 66 years) were included. A metabolic syndrome score was computed by summing the individual number of components according to the Adult Treatment Panel III criteria. We performed linear and logistic regression analysis and used standardized β-values to assess the association between metabolic syndrome and brain macrostructure (brain volume and white matter lesion load, lacunar infarcts, and cerebral microbleeds) and microstructure (mean magnetization transfer ratio [MTR], MTR histogram peak height, fractional anisotropy, and mean diffusivity [MD]). Linear and stepwise regression analysis was performed to identify the individual contribution of one metabolic syndrome parameter adjusting for the four other parameters. Models were adjusted for age, sex, and relation to long-lived family.Brain macrostructure was not associated with metabolic syndrome. In contrast, metabolic syndrome was associated with decreased gray (β = -0.3 P = 0.001) and white matter peak height (β = -0.3, P = 0.002) and increased gray matter MD (β = 0.2, P = 0.01, P = 0.01). Serum HDL cholesterol (β = 0.22, P = 0.012), triglycerides (β =-0.25, P = 0.002), BMI (β =-0.2, P = 0.014), and diastolic blood pressure (β = -0.17, P = 0.047, and β = -0.23, P = 0.009, for gray and white matter, respectively) were independent factors in these changes in brain microstructure.In early manifest metabolic syndrome, brain tissue decline can be detected. Serum HDL cholesterol, triglycerides, BMI, and diastolic blood pressure were independent factors in brain tissue integrity.
Cerebral small vessel disease (SVD) commonly accompanies aging and manifests on conventional MRI as white matter hyperintensities (WMH), subcortical infarcts (SI), microbleeds (CMBs), prominent perivascular spaces (PVS), and atrophy.1 Although these MRI markers may represent distinct pathophysiological aspects in SVD and have individually shown negative associations with cognition, they often occur together. We aimed to combine these structural imaging features in one measure to estimate total SVD burden and test for associations with incident cognitive disease in older people. The prospective population-based AGES-Reykjavik study assessed SVD features on brain MRI at baseline in 4333 participants aged 66–96 years without prevalent dementia. Presence of each of 5 MRI measures was given 1 point in a: WMH (dichotomised at the upper quintile), SI (0 vs. ≥1), CMBs (0 vs. ≥1), large PVS (0 vs. ≥1), and atrophy (dichotomised at the lower quintile). Participants underwent neuropsychological testing of verbal memory, processing speed and executive function, at baseline and a mean of 5.2 years later, and were followed up for incident dementia throughout the study period. We performed multiple linear-regression and Cox proportional-hazards analyses adjusted for education, major cerebrovascular risk factors and APOE ɛ4 genotype. We also used latent variable modelling to test whether the 5 MRI features form a single SVD construct in relation to cognitive decline. Total SVD score was significantly associated with a greater decline in all cognitive domains. Latent variable modeling suggested the 5 MRI markers formed a single construct, which showed consistent associations with cognitive decline compared with the SVD score. During 35168 person-years of follow-up, 842 participants developed dementia, of whom 397 had Alzheimer dementia (AD). Total SVD score was associated with an increased risk of all-cause dementia (hazard ratio, 1.32; 95% CI, 1.23–1.41, p<0.001) and AD (1.18; 1.07–1.31, p=0.001). Compared to those with a SVD score=0, participants with 4 or 5 points had highest risk of developing dementia (3.46; 2.33–5.14) and AD (2.55;1.33–4.87). The total SVD score is associated with cognitive decline and an increased risk of dementia in older people, showing construct validity and potential utility to comprehensively determine overall SVD-related brain damage.
Objective: To investigate progression of MRI-assessed manifestations of cerebral degeneration related to cognitive changes in a population of elderly patients with diabetes mellitus (DM) compared to age-matched control subjects. Methods: From a randomized controlled trial (PROSPER study), a study sample of 89 patients with DM and 438 control subjects without DM aged 70–82 years were included for brain MRI scanning and cognitive function testing at baseline and reexamination after 3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of infarctions, and cognitive function test results were determined in patients with DM and subjects without DM. Linear regression analysis was performed with correction for age, gender, hypertension, pravastatin treatment, educational level, and baseline test results. In patients with DM, baseline MRI parameters were correlated with change in cognitive function test result using linear regression analysis with covariates age and gender. Results: Patients with DM showed increased progression of brain atrophy (p < 0.01) after follow-up compared to control subjects. No difference in progression of WMH volume or infarctions was found. Patients with DM showed increased decline in cognitive performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore, in patients with DM, change in Picture Learning Test was associated with baseline brain atrophy (p < 0.02). Conclusion: Our data show that elderly patients with DM without dementia have accelerated progression of brain atrophy with significant consequences in cognition compared to subjects without DM. Our findings add further evidence to the hypothesis that diabetes exerts deleterious effects on neuronal integrity.
Method: In this study, 64/84 infants underwent follow-up at 2 years. Diffusion tensor imaging (DTI) values obtained around term were associated with a neurological examination and developmental scores (Bayley Scales-III). Cutoff values predicting motor delay and cerebral palsy were determined for fractional anisotropy (FA) and apparent diffusion coefficient (ADC).
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-systemic involvement. Nervous system involvement in SLE leads to a series of uncommon and heterogeneous neuropsychiatric (NP) manifestations. Current knowledge on the underlying pathogenic processes and their subsequent pathophysiological changes leading to NP-SLE manifestations is incomplete. Several putative laboratory biomarkers have been proposed as contributors to the genesis of SLE-related nervous system damage. Alongside the laboratory biomarkers, several neuroimaging tools have shown to reflect the nature of tissue microstructural damage associated with SLE, and thus were suggested to contribute to the understanding of the pathophysiological changes and subsequently help in clinical decision making. However, the number of useful biomarkers in NP-SLE in clinical practice is disconcertingly modest. In some cases it is not clear whether the biomarker is truly involved in pathogenesis, or the result of non-specific pathophysiological changes in the nervous system (e.g. neuroinflammation) or whether it is the consequence of a concomitant underlying abnormality related to SLE activity. In order to improve the diagnosis of NP-SLE and provide a better targeted care to these patients, there is still a need to develop and validate a range of biomarkers that reliably capture the different aspects of disease heterogeneity. This article critically reviews the current state of knowledge on laboratory and neuroimaging biomarkers in NP-SLE, discusses the factors that need to be addressed to make these biomarkers suitable for clinical application, and suggests potential future research paths to address important unmet needs in the NP-SLE field.
Background: Bee sting therapy is increasingly used to treat patients with multiple sclerosis (MS) in the belief that it can stabilize or ameliorate the disease. However, there are no clinical studies to justify its use. Methods: In a randomized, crossover study, we assigned 26 patients with relapsing-remitting or relapsing secondary progressive MS to 24 weeks of medically supervised bee sting therapy or 24 weeks of no treatment. Live bees (up to a maximum of 20) were used to administer bee venom three times per week. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on T1-weighted MRI of the brain. Secondary outcomes were lesion load on T2*-weighted MRI, relapse rate, disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Guy's Neurologic Disability Scale), fatigue (Abbreviated Fatigue Questionnaire, Fatigue Impact Scale), and health-related quality of life (Medical Outcomes Study 36-Item Short Form General Health Survey). Results: During bee sting therapy, there was no significant reduction in the cumulative number of new gadolinium-enhancing lesions. The T2*-weighted lesion load further progressed, and there was no significant reduction in relapse rate. There was no improvement of disability, fatigue, and quality of life. Bee sting therapy was well tolerated, and there were no serious adverse events. Conclusions: In this trial, treatment with bee venom in patients with relapsing multiple sclerosis did not reduce disease activity, disability, or fatigue and did not improve quality of life.
To prospectively investigate the patterns and rates of progression of magnetic resonance (MR) imaging abnormalities in a well-documented cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) cohort 7 years after baseline and to identify the prognostic factors that determine the rates and patterns of this progression.The local ethics committee approved the study, and informed consent was obtained from all participants. From 12 unrelated families, 25 patients who were NOTCH3 mutation carriers and 13 who were non-mutation carriers were examined clinically and with standardized MR imaging at baseline and after 7 years. The progression of white matter hyperintensities (WMHs), lacunar infarcts, microbleeding, and brain volume loss was measured semiquantitatively. Correlation testing and group comparison testing were performed to identify the risk factors associated with increased progression of CADASIL-related MR abnormalities.Compared with the non-mutation carriers, the mutation carriers showed significant increases in numbers of lacunar infarct (P < .01), WMH (P < .01), and microbleed (P < .05) lesions but no increased loss of brain volume. The distributions of new WMHs and new lacunar infarcts at follow-up were similar to the distributions of these abnormalities at baseline. High WMH (P < .05), lacunar infarct (P < .01), and microbleed (P < .01) lesion loads at baseline--but not cardiovascular risk factors--were associated with faster progression of these abnormalities.Patients with CADASIL who have a high MR abnormality lesion load at baseline are at risk for faster progression of MR abnormalities.
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