MATERIALS AND METHODS: In this study, DET (0.625. 1.25 and 2.5 mg/kg, i.p.) was administered in rats for 21 days and those animals were challenged with single injection of LPS (250 μg/kg, i.p.) for 7 days. Cognitive and behavioral assessment was carried out for 7 days followed by molecular assessment on brain hippocampus. Statistical significance was analyzed with one-way analysis of variance followed by Dunnett's test to compare the treatment groups with the control group.
KEY FINDINGS: DET ameliorated LPS-induced neuroinflammation by suppressing major pro-inflammatory mediators such as iNOS and COX-2. Furthermore, DET enhanced the anti-inflammatory cytokines and concomitantly suppressed the pro-inflammatory cytokines and chemokine production. DET treatment also reversed LPS-induced behavioral and memory deficits and attenuated LPS-induced elevation of the expression of AD markers. DET improved synaptic-functionality via enhancing the activity of pre- and post-synaptic markers, like PSD-95 and SYP. DET also prevented LPS-induced apoptotic neurodegeneration via inhibition of PARP-1, caspase-3 and cleaved caspase-3.
SIGNIFICANCE: Overall, our studies suggest DET can prevent neuroinflammation-associated memory impairment and neurodegeneration and it could be developed as a therapeutic agent for the treatment of neuroinflammation-mediated and neurodegenerative disorders, such as AD.
METHOD: Participants aged above 60 years from three ageing cohorts in Malaysia were interviewed virtually. The Fatigue, Resistance, Ambulation, Illness and Loss of Weight scale, blind Montreal Cognitive Assessment, 15-item Geriatric Depression Scale, anxiety subscale of Depression, Anxiety and Stress Scale and four-item Perceived Stress Scale measured frailty, mild cognitive impairment (MCI), depression, anxiety and stress, respectively.
RESULTS: Cognitive frailty data were available for 870 participants, age (mean ± SD) = 73.44 ± 6.32 years and 55.6% were women. Fifty-seven (6.6%) were robust, 24 (2.8%) had MCI, 451 (51.8%) were pre-frail, 164 (18.9%) were pre-frail+MCI, 119 (13.7%) were frail and 55 (6.3%) were frail+MCI. There were significant differences in depression and anxiety scores between the controlled MCO and recovery MCO. Using multinomial logistic regression, pre-frail (mean difference (95% confidence interval, CI) = 1.16 (0.932, 1.337), frail (1.49 (1.235, 1.803) and frail+MCI (1.49 (1.225, 1.822)) groups had significantly higher depression scores, frail (1.19 (1.030, 1.373)) and frail+MCI (1.24 (1.065, 1.439)) had significantly higher anxiety scores and pre-frail (1.50 (1.285, 1.761)), frail (1.74 (1.469, 2.062)) and frail+MCI (1.81 (1.508, 2.165)) had significantly higher stress scores upon adjustments for the potential confounders. The MCO was a potential confounder in the relationship between depression and prefrail+MCI (1.08 (0.898, 1.340)).
CONCLUSION: Frail individuals with or without MCI had significantly higher depression, anxiety and stress than those who were robust. Increased depression and stress were also observed in the pre-frail group. Interventions to address psychological issues in older adults during the COVID-19 pandemic could target prefrail and frail individuals and need further evaluation.
CONCLUSION: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.
RECENT FINDINGS: Methods of acquisition and analysis of BPV and cognitive measurements and their relationship were extracted from selected articles. Of 656 studies identified, 53 articles were selected. Twenty-five evaluated long-term (LTBPV), nine mid-term (MTBPV), 12 short-term (STBPV) and nine very short-term BPV (VSTBPV) with conflicting findings on the relationship between BPV and cognition. Variations existed in devices, period and procedure for acquisition. The studies also utilized a wide range of methods of BPV calculation. Thirteen cognitive assessment tools were used to measure global cognition or domain functions which were influenced by the population of interest. The interpretation of available studies was hence limited by heterogeneity. There is an urgent need for standardization of BPV assessments to streamline research on BPV and cognition. Future studies should also establish whether BPV could be a potential modifiable risk factor for cognitive decline, as well as a marker for treatment response.
METHODS: Data was obtained from the Malaysian Elders Longitudinal Research (MELoR) study, which employed random stratified sampling from three parliamentary constituencies within the Klang Valley. Beat-to-beat blood pressure (BP) was recorded using non-invasive BP monitoring (TaskforceTM, CNSystems). Low frequency (LF), high frequency (HF) and low-to-high frequency (LF:HF) ratio for BPV were derived using fast Fourier transformation. Cognition was evaluated using the Montreal Cognitive Assessment (MoCA) test, and categorized into normal aging, mild impairment and moderate-to-severe impairment.
RESULTS: Data from 1,140 individuals, mean age (SD) 68.48 (7.23) years, were included. Individuals with moderate-to-severe impairment had higher HF-BPV for systolic (SBP) and diastolic (DBP) blood pressure compared to individuals within the normal aging group [OR (95% CI) = 2.29 (1.62-3.24)] and [OR (95% CI) = 1.80 (1.32-2.45)], while HF-SBPV [OR (95% CI) = 1.41 (1.03-1.93)] but not HF-DBPV was significantly higher with mild impairment compared to normal aging after adjustments for potential confounders. Moderate-to-severe impairment was associated with significantly lower LF:HF-SBPV [OR (95% CI) = 0.29 (0.18-0.47)] and LF:HF-DBPV [OR (95% CI) = 0.49 (0.34-0.72)], while mild impairment was associated with significantly lower LF:HF-SBPV [OR (95% CI) = 0.52 (0.34-0.80)] but not LF:HF-DBPV [OR (95% CI) = 0.81 (0.57-1.17)], compared to normal aging with similar adjustments.
CONCLUSION: Higher HF-BPV, which indicates parasympathetic activation, and lower LF:HF-BPV, which addresses sympathovagal balance, were observed among individuals with moderate-to-severe cognitive impairment. Future studies should determine whether BPV could be a physiological marker or modifiable risk factor for cognitive decline.