Restricted accessResearch articleFirst published online 2024-12
Associations among healthy lifestyle characteristics,neuroinflammation,and cerebrospinal fluid core biomarkers of Alzheimer's disease in cognitively intact adults: The CABLE study
The occurrence of Alzheimer's disease (AD) can be partially prevented through healthy lifestyles, but the mechanisms associated with AD pathology are unclear.
Objective
To explore associations among healthy lifestyle characteristics (HLCs), cerebrospinal fluid (CSF) soluble TREM2 (sTREM2), and AD biomarkers.
Methods
From the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, 924 cognitively normal participants were enrolled in this cross-sectional analysis. We defined the following 11 HLCs: appropriate frequencies of coffee and tea consumption, sufficient frequencies of fish and fruit intake, non-social isolation, adequate sleep, regular physical activity, no depression, never smoking, non-hazardous drinking, and well-maintained blood pressure. We categorized participants according to the number of HLCs reported by participants into favorable, intermediate, and unfavorable lifestyle groups. Multiple linear regression was used to investigate the relationship among HLCs, CSF sTREM2, and AD biomarkers. Mediation effects were tested using a causal mediation analysis having 10,000 bootstrap iterations.
Results
Included subjects were with a mean age of 61.8 ± 10.2 years, of which 41.8% were female. Sufficient fish intake (β = −0.164, p = 0.017) and well-maintained blood pressure (β = −0.232, p = 0.006) were significantly correlated with lower CSF sTREM2 levels. A larger number of HLCs were associated with lower CSF T-tau (p = 0.001), P-tau (p = 0.012), and sTREM2 (p = 0.040) levels. CSF sTREM2 partially mediated the association between the number of HLCs and CSF tau pathology (mediating proportion T-tau: 22.4%; P-tau: 25.0%).
Conclusions
HLCs might impact the pathological processes of AD by regulating neuroinflammation.
GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019. Lancet Public Health2022; 7: e105–e125.
2.
2023 Alzheimer's disease facts and figures. Alzheimers Dement2023; 19: 1598–1695.
3.
ReevesMJRaffertyAP. Healthy lifestyle characteristics among adults in the United States, 2000. Arch Intern Med2005; 165: 854–857.
4.
ZhangYYangHLiS, et al.Consumption of coffee and tea and risk of developing stroke, dementia, and poststroke dementia: a cohort study in the UK Biobank. PLoS Med2021; 18: e1003830.
5.
IslamMRValarisSYoungMF, et al.Exercise hormone irisin is a critical regulator of cognitive function. Nat Metab2021; 3: 1058–1070.
6.
SabiaSFayosseADumurgierJ, et al.Association of sleep duration in middle and old age with incidence of dementia. Nat Commun2021; 12: 10.
7.
UngvariZTothPTarantiniS, et al.Hypertension-induced cognitive impairment: from pathophysiology to public health. Nat Rev Nephrol2021; 17: 639–654.
8.
GuYLuchsingerJASternY, et al.Mediterranean Diet, inflammatory and metabolic biomarkers, and risk of Alzheimer's disease. J Alzheimers Dis2010; 22: 483–492.
9.
LangballeEMAskHHolmenJ, et al.Alcohol consumption and risk of dementia up to 27 years later in a large, population-based sample: the HUNT study, Norway. Eur J Epidemiol2015; 30: 1049–1056.
10.
Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines. Geneva: World Health Organization, 2019.
11.
ReijsBLRVosSJBSoininenH, et al.Association between later life lifestyle factors and Alzheimer's disease biomarkers in non-demented individuals: a longitudinal descriptive cohort study. J Alzheimers Dis2017; 60: 1387–1395.
12.
HouXHXuWBiYL, et al.Associations of healthy lifestyles with cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: the CABLE study. Alzheimers Res Ther2021; 13: 8.
13.
ZhaoYLOuYNMaYH, et al.Association between life's simple 7 and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: the CABLE study. Alzheimers Res Ther2022; 14: 74.
14.
BrownBMPeifferJRainey-SmithSR. Exploring the relationship between physical activity, beta-amyloid and tau: a narrative review. Ageing Res Rev2019; 50: 9–18.
15.
EikelenboomPVeerhuisRvan ExelE, et al.The early involvement of the innate immunity in the pathogenesis of late-onset Alzheimer's disease: neuropathological, epidemiological and genetic evidence. Curr Alzheimer Res2011; 8: 142–150.
16.
SarlusHHenekaMT. Microglia in Alzheimer's disease. J Clin Invest2017; 127: 3240–3249.
17.
HickmanSEKingeryNDOhsumiTK, et al.The microglial sensome revealed by direct RNA sequencing. Nat Neurosci2013; 16: 1896–1905.
18.
KleinbergerGYamanishiYSuarez-CalvetM, et al.TREM2 Mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med2014; 6: 12.
19.
ColonnaMWangYM. TREM2 Variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci2016; 17: 201–207.
20.
Suárez-CalvetMKleinbergerGCaballeroMAA, et al.sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers. EMBO Mol Med2016; 8: 466–476.
21.
MadoreCYinZRLeibowitzJ, et al.Microglia, lifestyle stress, and neurodegeneration. Immunity2020; 52: 222–240.
22.
CuiGHYaoYHXuRF, et al.Cognitive impairment using education-based cutoff points for CMMSE scores in elderly Chinese people of agricultural and rural Shanghai China. Acta Neurol Scand2011; 124: 361–367.
23.
WinerJRDetersKDKennedyG, et al.Association of short and long sleep duration with amyloid-β burden and cognition in aging. JAMA Neurol2021; 78: 1187–1196.
24.
MorrisMCEvansDATangneyCC, et al.Fish consumption and cognitive decline with age in a large community study. Arch Neurol2005; 62: 1849–1853.
25.
PolidoriMCPraticoDMangialascheF, et al.High fruit and vegetable intake is positively correlated with antioxidant status and cognitive performance in healthy subjects. J Alzheimers Dis2009; 17: 921–927.
26.
EskelinenMHNganduTTuomilehtoJ, et al.Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. J Alzheimers Dis2009; 16: 85–91.
27.
DesaiRJohnAStottJ, et al.Living alone and risk of dementia: a systematic review and meta-analysis. Ageing Res Rev2020; 62: 101122.
28.
ByersALYaffeK. Depression and risk of developing dementia. Nat Rev Neurol2011; 7: 323–331.
29.
OttASlooterAJHofmanA, et al.Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam study. Lancet1998; 351: 1840–1843.
30.
RanLSLiuWHFangYY, et al.Alcohol, coffee and tea intake and the risk of cognitive deficits: a dose-response meta-analysis. Epidemiol Psychiatr Sci2021; 30: e13.
31.
WuMSLanTHChenCM, et al.Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan. BMC Public Health2011; 11: 22.
32.
MaQPHuangCCuiQY, et al.Meta-analysis of the association between tea intake and the risk of cognitive disorders. PLoS One2016; 11: e0165861.
33.
American Heart Association Nutrition Committee, LichtensteinAHAppelLJ, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association nutrition committee. Circulation2006; 114: 82–96.
34.
Consensus Conference P, WatsonNFBadrMS, et al.Joint consensus statement of the American academy of sleep medicine and sleep research society on the recommended amount of sleep for a healthy adult: methodology and discussion. J Clin Sleep Med2015; 11: 931–952.
35.
MulsantBHSweetRRifaiAH, et al.The use of the Hamilton rating scale for depression in elderly patients with cognitive impairment and physical illness. Am J Geriatr Psychiatry1994; 2: 220–229.
36.
WangZTLiKYTanCC, et al.Associations of alcohol consumption with cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: the CABLE study. J Alzheimers Dis2021; 82: 1045–1054.
37.
Lloyd-JonesDMHongYLabartheD, et al.Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic impact goal through 2020 and beyond. Circulation2010; 121: 586–613.
38.
Gervaise-HenryCWatfaGAlbuissonE, et al.Cerebrospinal fluid Abeta42/abeta40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis2017; 57: 437–445.
39.
BaronRMKennyDA. The moderator mediator variable distinction in social psychological-research - conceptual, strategic, and statistical considerations. J Pers Soc Psychol1986; 51: 1173–1182.
40.
ChenPChenFLeiJ, et al.Pomegranate polyphenol punicalagin improves learning memory deficits, redox homeostasis, and neuroinflammation in aging mice. Phytother Res2023; 37: 3655–3674.
41.
CharriereKGhzaielILizardG, et al.Involvement of microglia in neurodegenerative diseases: beneficial effects of docosahexahenoic acid (DHA) supplied by food or combined with nanoparticles. Int J Mol Sci2021; 22: 26.
42.
HuFB. Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol2002; 13: 3–9.
43.
GuYNievesJWSternY, et al.Food combination and Alzheimer disease risk: a protective diet. Arch Neurol2010; 67: 699–706.
44.
MahaffeyKRClicknerRPJeffriesRA. Methylmercury and omega-3 fatty acids: co-occurrence of dietary sources with emphasis on fish and shellfish. Environ Res2008; 107: 20–29.
45.
TanZSHarrisWSBeiserAS, et al.Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology2012; 78: 658–664.
46.
TangneyCCLiHWangY, et al.Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology2014; 83: 1410–1416.
47.
SolfrizziVAgostiPLozuponeM, et al.Nutritional intervention as a preventive approach for cognitive-related outcomes in cognitively healthy older adults: a systematic review. J Alzheimers Dis2018; 64: S229–S254.
48.
PanzaFLa MontagnaMLampignanoL, et al.Vitamin D in the development and progression of Alzheimer's disease: implications for clinical management. Expert Rev Neurother2021; 21: 287–301.
49.
HuHMengLBiYL, et al.Tau pathologies mediate the association of blood pressure with cognitive impairment in adults without dementia: the CABLE study. Alzheimers Dement2022; 18: 53–64.
50.
ShenLXYangYXKuoK, et al.Social isolation, social interaction, and Alzheimer's disease: a Mendelian randomization study. J Alzheimers Dis2021; 80: 665–672.
51.
SchwarzbachMLuppaMForstmeierS, et al.Social relations and depression in late life-a systematic review. Int J Geriatr Psychiatry2014; 29: 1–21.
52.
Valverde-SalazarVRuiz-GabarreDGarcia-EscuderoV. Alzheimer's disease and green tea: epigallocatechin-3-gallate as a modulator of inflammation and oxidative stress. Antioxidants (Basel)2023; 12: 1460.
53.
Basurto-IslasGBlanchardJTungYC, et al.Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease. Neurobiol Aging2014; 35: 2701–2712.
54.
PolitoCACaiZYShiYL, et al.Association of tea consumption with risk of Alzheimer's disease and anti-beta-amyloid effects of tea. Nutrients2018; 10: 18.
55.
Lopez-OrtizSPinto-FragaJValenzuelaPL, et al.Physical exercise and Alzheimer's disease: effects on pathophysiological molecular pathways of the disease. Int J Mol Sci2021; 22: 2897.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
