Regular exercise reduces risk of dementia and Alzheimer's disease
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PROVIDER: S-EPMC1336790 | biostudies-literature | 2006 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionMild to moderate exercise may decrease Alzheimer's disease (AD) risk, but the effects of vigorous, regular physical exercise remain unclear.MethodsTwo patients with initial diagnoses of amnestic mild cognitive impairment (MCI) demonstrated positive AD biomarkers throughout 16 and 8 years of follow-up, with final diagnoses of mild AD and amnestic MCI, respectively.ResultsPatient 1 was diagnosed with amnestic MCI at age 64. Neuropsychological testing, magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid imaging PET, and cerebrospinal fluid (CSF) biomarkers during follow-ups remained consistent with AD. By age 80, progression was minimal with Montreal Cognitive Assessment (MoCA) 26 of 30. Patient 2 was diagnosed with amnestic MCI at age 72. Neuropsychological testing, MRI, FDG-PET, and amyloid imaging PET during follow-ups remained consistent with AD. At age 80, MoCA was 27 of 30 with no clinical progression. Both patients regularly performed vigorous, regular exercise that increased after retirement/work reduction.DiscussionVigorous, regular exercise may slow disease progression in biomarker-positive amnestic MCI and mild AD.
| S-EPMC10101862 | biostudies-literature
Project description:Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer's disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.
| S-EPMC8395833 | biostudies-literature
Project description:IntroductionLewy body dementia (LBD) shares genetic risk factors with Alzheimer's disease (AD), including apolipoprotein E (APOE), but is distinguishable at the genome-wide level. Polygenic risk scores (PRS) may therefore improve diagnostic classification.MethodsWe assessed diagnostic classification using AD-PRS excluding APOE (AD-PRSno APOE), APOE risk score (APOE-RS), and plasma phosphorylated tau 181 (p-tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (Aβ)positive mild cognitive impairment or AD (MCI+/AD), and 57 controls.ResultsTogether AD-PRSno APOE and APOE-RS performed similarly to p-tau181 in discriminating MCI+/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, Aβ positivity was significantly associated with APOE-RS, but not with AD-PRSno APOE, or p-tau181. Combining AD-PRSno APOE, APOE-RS, and p-tau181 improved the discrimination of MCI+/AD from controls (81%) and LBD (75%), and the detection of Aβ in LBD (82%).DiscussionAβ deposition in LBD was associated with APOE, while MCI+/AD was also associated with AD-PRS beyond APOE. AD-PRS explains phenotypic variance not captured by APOE or p-tau181.HighlightsWe investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (APOE), and plasma phosphorylated tau 181 (p-tau181) to classify AD and Lewy body dementia (LBD). AD-PRS with APOE achieved similar classification accuracy to p-tau181. AD-PRS without APOE significantly contributed to discriminating AD from LBD. Amyloid beta positivity in LBD was associated with APOE but not AD-PRS without APOE or p-tau181. Combining AD-PRS, APOE, and p-tau181 improved diagnostic classification accuracy.
| S-EPMC11848393 | biostudies-literature
Project description:The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
| S-EPMC6660501 | biostudies-literature
Project description:We recently showed that Western diet-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female Western diet-fed mice. Four-week-old C57BL/6 mice were randomized into sedentary (ie, caged confined, n=6) or regular exercise (ie, access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition. Compared with sedentary mice, exercise-trained mice exhibited reduced endothelial cortical stiffness in aortic explants (sedentary 11.9±1.7 kPa versus exercise 5.5±1.0 kPa; P<0.05), as assessed by atomic force microscopy. This effect of exercise was not accompanied by changes in aortic pulse wave velocity (P>0.05), an in vivo measure of aortic stiffness. In comparison, exercise reduced femoral artery stiffness in isolated pressurized arteries and led to an increase in femoral internal artery diameter and wall cross-sectional area (P<0.05), indicative of outward hypertrophic remodeling. These effects of exercise were associated with an increase in femoral artery elastin content and increased number of fenestrae in the internal elastic lamina (P<0.05). Collectively, these data demonstrate for the first time that the aortic endothelium is highly plastic and, thus, amenable to reductions in stiffness with regular aerobic exercise in the absence of changes in in vivo whole aortic stiffness. Comparatively, the same level of exercise caused destiffening effects in peripheral muscular arteries, such as the femoral artery, that perfuse the working limbs.
| S-EPMC5063712 | biostudies-literature
Project description:ObjectiveWe evaluated dementia and Alzheimer's disease (AD) risks after a cancer diagnosis in a population-based prospective cohort, the Adult Changes in Thought (ACT) study.MethodsWe followed community-dwelling people aged ≥65 years without dementia at study entry for incident dementia and AD from 1994-2015. We linked study data with cancer registry data and categorized cancer diagnoses as prevalent (diagnosed before ACT study enrollment) or incident (diagnosed during follow-up). We used Cox regression to estimate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for dementia or AD risk comparing people with a cancer diagnosis to people without cancer. We conducted sensitivity analyses restricted to people surviving beyond age 80, and stratified by cancer stage, type, and whether the cancer was smoking-related.ResultsAmong 4,357 people, 756 (17.4%) had prevalent cancer; 583 (13.4%) developed incident cancer, 1,091 (25.0%) developed dementia, and 877 (20.1%) developed AD over a median 6.4 years (34,482 total person-years) of follow-up. Among complete cases (no missing covariates) with at least one follow-up assessment, adjusted HRs for dementia following prevalent and incident cancer diagnoses were 0.92 (95%CI: 0.76, 1.11) and 0.87 (95%CI: 0.64, 1.04), compared to no cancer history. HRs for AD were 0.95 (95%CI: 0.77, 1.17) for prevalent cancer and 0.73 (95%CI: 0.55, 0.96) for incident cancer. In sensitivity analyses, prevalent late-stage cancers were associated with reduced risks of dementia (HR = 0.51, 95%CI: 0.30, 0.89) and AD (HR = 0.50, 95%CI: 0.27, 0.94). When limited to people who survived beyond age 80, incident cancers were still associated with reduced AD risk (HR = 0.69, 95%CI: 0.51, 0.92).ConclusionsOur results do not support an inverse association between prevalent cancer diagnoses, which were primarily early-stage, less aggressive cancers, and risk of dementia or AD. A reduced risk of AD following an incident cancer diagnosis is biologically plausible but may reflect selective mortality.
| S-EPMC5478144 | biostudies-literature
Project description:ObjectivesThe association between gout and dementia, Alzheimer's disease (AD), or vascular dementia (VD) is not fully understood. The aim of this meta-analysis was to evaluate the risk of all-cause dementia, AD, and VD in gout patients with or without medication.MethodsData sources were PubMed, Embase, the Cochrane Library, and reference lists of included studies. This meta-analysis included cohort studies assessing whether the risk of all-cause dementia, AD, and VD was associated with gout. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to access the overall certainty of evidence. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test.ResultsA total of six cohort studies involving 2,349,605 individuals were included in this meta-analysis, which were published between 2015 and 2022. The pooling analysis shows that the risk of all-cause dementia was decreased in gout patients [RR = 0.67, 95% CI (0.51, 0.89), I2 = 99%, P = 0.005, very low quality], especially in gout patients with medication [RR = 0.50, 95% CI (0.31, 0.79), I2 = 93%, P = 0.003, low quality]. The risk of AD [RR = 0.70, 95% CI (0.63, 0.79), I2 = 57.2%, P = 0.000, very low quality] and VD [RR = 0.68, 95% CI (0.49, 0.95), I2 = 91.2%, P = 0.025, very low quality] was also decreased in gout patients. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias.ConclusionThe risk of all-cause dementia, AD, and VD is decreased in gout patients, but the quality of evidence is generally low. More studies are still needed to validate and explore the mechanisms of this association.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022353312.
| S-EPMC10169719 | biostudies-literature
Project description:This study examines whether neuroticism is differentially associated with risk of incident Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD) using a prospective study design. Participants from the UK Biobank (N = 401,422) completed a self-report neuroticism scale in 2006-2010 and incident all-cause dementia, AD, VD, and FTD were ascertained using electronic health records or death records up to 2018. During an average follow-up of 8.8 years (3,566,123 person-years), there were 1798 incident of all-cause dementia, 675 AD, 376 VD, and 81 FTD. Accounting for age and sex, compared to individuals in the low quartile, individuals in the top quartile of neuroticism had higher risk of all-cause dementia (HR = 1.70; 95% CI: 1.49-1.93), AD (HR = 1.42; 1.15-1.75), VD (HR = 1.73; 1.30-2.29), but not FTD (HR = 0.89; 0.49-1.63). The associations with AD and VD were attenuated but remained significant after further accounting for education, household income, deprivation index, diabetes, hypertension, stroke, heart attack, ever smoker, physical activity, obesity, hemoglobin A1c, C-reactive protein, and low-density lipoprotein. The associations were not moderated by socioeconomic status. The findings were consistent in analyses that excluded cases that occurred within the first 5 years of follow-up. In conclusion, neuroticism is a robust predictor of incident AD and VD, but not FTD. This pattern suggests that the affective symptoms that distinguish dementia types may partly reflect premorbid differences in trait neuroticism.
| S-EPMC8192471 | biostudies-literature
Project description:PurposeDifferentiating between Alzheimer's disease (AD) and frontotemporal dementia (FTD) can be challenging due to overlapping cognitive and behavioral manifestations. Evidence regarding non-invasive and early-stage biomarkers remains limited. Our aim was to identify retinal biomarkers for the risk of AD and FTD in populations without dementia and explore underlying brain structural mechanisms.MethodsWe included a total of 3,0573 UK Biobank participants without dementia, ocular disorders, and diabetes who underwent baseline retinal optical coherence tomography (OCT) imaging. Cox proportional hazards models were used to estimate the associations between macular OCT parameters and the risk of AD and FTD. Mediation analysis was used to explore the underlying mechanisms affected by brain structures.ResultsThe mean age at recruitment was 55.27, and 46.10% of the participants were male. During a mean follow-up of 9.15 ± 2.59 years, 148 patients with AD and eight patients with FTD were identified. Reduced thickness of the ganglion cell-inner plexiform layer (GC-IPL) at baseline was associated with an increased risk of AD (HR, 1.033; 95% CI, 1.001-1.066; P = 0.044), while thinner retinal pigment epithelial in the inner superior subfield at baseline was associated with an elevated risk of FTD (HR, 1.409; 95% CI, 1.060-1.871; P = 0.018). Structurally abnormal visual pathways, including cortical and subcortical gray matter volumes, as well as white matter integrity, mediated the association between the GC-IPL thickness and AD risk.ConclusionOur findings provide preliminary empirical support for a relationship between prodromal changes in retinal layers and a higher risk of AD or FTD, suggesting that macular OCT may serve as a non-invasive, sensitive biomarker of high-risk years before the onset of dementia.
| S-EPMC11759267 | biostudies-literature
Project description:This article will review the recent advances in the understanding of the role of epigenetic modifications and the promise of future epigenetic therapy in neurodegenerative dementias, including Alzheimer's disease and frontotemporal dementia.
| S-EPMC3805876 | biostudies-other