Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma

BACKGROUND: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. METHODS: Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. RESULTS: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. CONCLUSION: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD

Quantitative Electroencephalography Analyzed by Statistical Pattern Recognition as a Diagnostic and Prognostic Tool in Mild Cognitive Impairment:Results from a Nordic Multicenter Cohort Study

Aim: To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. Methods: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. Results: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. Conclusion: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD

Associations between sleep quality and biomarkers for neurodegeneration - A longitudinal one-year case-control study of patients with bipolar disorder and healthy control individuals

Disturbed sleep during affective episodes may impact levels of cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42 and other biomarkers of neurodegeneration in patients with bipolar disorder (BD). The study aimed to investigate the correlations between sleep and biomarkers for Alzheimer's disease (AD) and neurodegeneration in BD and healthy controls (HC). We present a prospective, longitudinal case-control study of euthymic patients with BD (N ​= ​86) and HC (N ​= ​44). All participants were evaluated with clinical assessments at baseline, and after a year. The patients’ affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. Patients were re-assessed during and after an episode if it occurred during follow-up. Total sleep scores based on three Hamilton-17 Depression Scale items were analyzed in relation to concentrations of CSF-Aβ42, CSF-Aβ40, CSF-Aβ38, CSF-Aβ42/40 and 42/38 ratios, CSF-soluble amyloid-precursor proteins α+β, plasma-Aβ42, plasma-Aβ40, CSF-phosphorylated-tau, CSF-total-tau, plasma-total-tau, CSF-neurofilament-light, plasma-neurofilament-light, CSF-neurogranin, serum-S100B, CSF-8-oxo-7,8-dihydro-guanosine, CSF-8-oxo-7,8-dihydro-2′-deoxyguanosine, urine-8-oxo-7,8-dihydro-guanosine, and urine-8-oxo-7,8-dihydro-2′-deoxyguanosine. The primary outcome was the association between total sleep scores and levels of CSF-Aβ42 at baseline and follow-up estimated by the regression coefficient in a linear mixed model. We found no statistically significant associations between sleep and CSF-Aβ42 (−2.307 ​pg/ml (95% CI: -9.525–4.911; p ​= ​0.523)) or any other biomarkers. However, higher sleep scores appeared to be associated with higher CSF-Aβ42/40 and CSF-Aβ42/38 ratios, and lower CSF-total-tau concentration, but were not statistically significant after correction for multiple testing. In conclusion attenuated sleep during an affective episode was not associated with changes in biomarkers for AD and neurodegeneration in BD, but larger prospective studies are needed