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Open Access 01-04-2021 | Original Article

When your brain looks older than expected: combined lifestyle risk and BrainAGE

Authors: Nora Bittner, Christiane Jockwitz, Katja Franke, Christian Gaser, Susanne Moebus, Ute J. Bayen, Katrin Amunts, Svenja Caspers

Published in: Brain Structure and Function | Issue 3/2021

Abstract

Lifestyle may be one source of unexplained variance in the great interindividual variability of the brain in age-related structural differences. While physical and social activity may protect against structural decline, other lifestyle behaviors may be accelerating factors. We examined whether riskier lifestyle correlates with accelerated brain aging using the BrainAGE score in 622 older adults from the 1000BRAINS cohort. Lifestyle was measured using a combined lifestyle risk score, composed of risk (smoking, alcohol intake) and protective variables (social integration and physical activity). We estimated individual BrainAGE from T1-weighted MRI data indicating accelerated brain atrophy by higher values. Then, the effect of combined lifestyle risk and individual lifestyle variables was regressed against BrainAGE. One unit increase in combined lifestyle risk predicted 5.04 months of additional BrainAGE. This prediction was driven by smoking (0.6 additional months of BrainAGE per pack-year) and physical activity (0.55 less months in BrainAGE per metabolic equivalent). Stratification by sex revealed a stronger association between physical activity and BrainAGE in males than females. Overall, our observations may be helpful with regard to lifestyle-related tailored prevention measures that slow changes in brain structure in older adults.

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Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, Leon AS (2000) Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 32(9 SUPP 1):S498–S516. https://doi.org/10.1097/00005768-200009001-00009CrossRefPubMed

Almeida OP, Garrido GJ, Lautenschlager NT, Hulse GK, Jamrozik K, Flicker L (2008) Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease. Am J Geriatr Psychiatry 16(1):92–98PubMedCrossRef

Anaturk M, Demnitz N, Ebmeier KP, Sexton CE (2018) A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults. Neurosci Biobehav Rev 93:71–84. https://doi.org/10.1016/j.neubiorev.2018.06.012CrossRefPubMedPubMedCentral

Arenaza-Urquijo EM, Wirth M, Chetelat G (2015) Cognitive reserve and lifestyle: moving towards preclinical Alzheimer’s disease. Front Aging Neurosci 7:134. https://doi.org/10.3389/fnagi.2015.00134CrossRefPubMedPubMedCentral

Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839–851. https://doi.org/10.1016/j.neuroimage.2005.02.018CrossRefPubMed

Bamberg F, Kauczor HU, Weckbach S, Schlett CL, Forsting M, Ladd SC, Pischon T (2015) Whole-body MR imaging in the German National Cohort: rationale, design, and technical background. Radiology 277(1):206–220PubMedCrossRef

Bartrés-Faz D, Arenaza-Urquijo EM (2011) Structural and functional imaging correlates of cognitive and brain reserve hypotheses in healthy and pathological aging. Brain Topogr 24(3–4):340–357. https://doi.org/10.1007/s10548-011-0195-9CrossRefPubMed

Bennett KP, Campbell C (2000) Support vector machines: hype or hallelujah? ACM SIGKDD Explor Newsl 2(2):1–13CrossRef

Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS (2006) The effect of social networks on the relation between Alzheimer’s disease pathology and level of cognitive function in old people: a longitudinal cohort study. Lancet Neurol 5(5):406–412. https://doi.org/10.1016/s1474-4422(06)70417-3CrossRefPubMed

Berkman LF (2004) Social integration and mortality: a prospective study of French employees of electricity of France-gas of France: The GAZEL cohort. Am J Epidemiol 159(2):167–174. https://doi.org/10.1093/aje/kwh020CrossRefPubMed

Bickart KC, Wright CI, Dautoff RJ, Dickerson BC, Barrett LF (2011) Amygdala volume and social network size in humans. Nat Neurosci 14(2):163–164. https://doi.org/10.1038/nn.2724CrossRefPubMed

Bittner N, Jockwitz C, Mühleisen TW, Hoffstaedter F, Eickhoff SB, Moebus S, Bayen UJ, Cichon S, Zilles K, Amunts K, Caspers S (2019) Combining lifestyle risks to disentangle brain structure and functional connectivity differences in older adults. Nat Commun 10(1):621. https://doi.org/10.1038/s41467-019-08500-xCrossRefPubMedPubMedCentral

Boyke J, Driemeyer J, Gaser C, Buchel C, May A (2008) Training-induced brain structure changes in the elderly. J Neurosci 28(28):7031–7035. https://doi.org/10.1523/JNEUROSCI.0742-08.2008CrossRefPubMedPubMedCentral

Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, London ED (2004) Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiat 55(1):77–84. https://doi.org/10.1016/s0006-3223(03)00610-3CrossRefPubMed

Bugg JM, Head D (2011) Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol aging 32(3):506–514PubMedCrossRef

Burd NA, Tang JE, Moore DR, Phillips SM (2009) Exercise training and protein metabolism: influences of contraction, protein intake, and sex-based differences. J Appl Physiol 106(5):1692–1701. https://doi.org/10.1152/japplphysiol.91351.2008CrossRefPubMed

Bus BA, Molendijk ML, Penninx BJ, Buitelaar JK, Kenis G, Prickaerts J, Voshaar RC (2011) Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology 36(2):228–239. https://doi.org/10.1016/j.psyneuen.2010.07.013CrossRefPubMed

Bzdok D, Ioannidis JP (2019) Exploration, inference, and prediction in neuroscience and biomedicine. Trends Neurosci 42(4):251–262PubMedCrossRef

Carstensen LL, Isaacowitz DM, Charles ST (1999) Taking time seriously: a theory of socioemotional selectivity. Am Psychol 54(3):165PubMedCrossRef

Caspers S, Moebus S, Lux S, Pundt N, Schutz H, Muhleisen TW, Amunts K (2014) Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS. Front Aging Neurosci 6(149):1–14. https://doi.org/10.3389/fnagi.2014.00149CrossRef

Christensen H, Anstey KJ, Leach LS, Mackinnon AJ (2008) Intelligence, education, and the brain reserve hypothesis. In: Craik FIM, Salthouse TA (eds) The handbook of aging and cognition, 3rd edn. Psychology Press, New York, pp 133–188

Christie GJ, Hamilton T, Manor BD, Farb NAS, Farzan F, Sixsmith A, Moreno S (2017) Do lifestyle activities protect against cognitive decline in aging? A review. Front Aging Neurosci 9:381. https://doi.org/10.3389/fnagi.2017.00381CrossRefPubMedPubMedCentral

Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF, Greenough WT (2002) Exercise, experience and the aging brain. Neurobiol Aging 23(5):941–955PubMedCrossRef

Colcombe SJ, Kramer AF (2003) Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14(2):125–130PubMedCrossRef

Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, Kramer AF (2003) Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol Ser A Biol Sci Med Sci 58(2):176–180CrossRef

Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Elavsky S (2004) Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci 101(9):3316–3321. https://doi.org/10.1073/pnas.0400266101CrossRefPubMedPubMedCentral

Cole JH, Franke K (2017) Predicting age using neuroimaging: innovative brain ageing biomarkers. Trends Neurosci 40(12):681–690. https://doi.org/10.1016/j.tins.2017.10.001CrossRefPubMed

Cole JH, Leech R, Sharp DJ, Alzheimer´s Disease neuroimaging Initiative (ADNI) (2015) Prediction of brain age suggests accelerated atrophy after traumatic brain injury. Ann Neurol 77(4):571–581PubMedPubMedCentralCrossRef

Cole JH, Franke K, Cherbuin N (2019) Quantification of the biological age of the brain using neuroimaging. Biomarkers of Human Aging. Springer, New York, pp 293–328CrossRef

Cohen J (2013) Statistical power analysis for the behavioral sciences. Academic press

Cosgrove KP, Mazure CM, Staley JK (2007) Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry 62(8):847–855. https://doi.org/10.1016/j.biopsych.2007.03.001CrossRefPubMedPubMedCentral

Cuadra MB, Cammoun L, Butz T, Cuisenaire O, Thiran JP (2005) Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images. IEEE Trans Med Imaging 24(12):1548–1565. https://doi.org/10.1109/TMI.2005.857652CrossRefPubMed

Cullen KR, Wallace S, Magnotta VA, Bockholt J, Ehrlich S, Gollub RL, White T (2012) Cigarette smoking and white matter microstructure in schizophrenia. Psychiatry Res 201(2):152–158. https://doi.org/10.1016/j.pscychresns.2011.08.010CrossRefPubMedPubMedCentral

de la Monte SM, Kril JJ (2014) Human alcohol-related neuropathology. Acta Neuropathol 127(1):71–90. https://doi.org/10.1007/s00401-013-1233-3CrossRefPubMed

de Melo Coelho FG, Gobbi S, Andreatto CAA, Corazza DI, Pedroso RV, Santos-Galduróz RF (2013) Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr 56(1):10–15. https://doi.org/10.1016/j.archger.2012.06.003CrossRef

Del Boca FK, Darkes J (2003) The validity of self-reports of alcohol consumption: state of the science and challenges for research. Addiction 98:1–12PubMedCrossRef

den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, van Duijn CM, Breteler MM (2004) Alcohol intake in relation to brain magnetic resonance imaging findings in older persons without dementia. Am J Clin Nutr 80(4):992–997CrossRef

Dickie DA, Job DE, Gonzalez DR, Shenkin SD, Ahearn TS, Murray AD, Wardlaw JM (2013) Variance in brain volume with advancing age: implications for defining the limits of normality. PLoS ONE 8(12):e84093. https://doi.org/10.1371/journal.pone.0084093CrossRefPubMedPubMedCentral

Draganski B, Gaser C, Busch V, Schuierer G, Bogdahn U, May A (2004) Neuroplasticity: changes in grey matter induced by training. Nature 427(6972):311–312PubMedCrossRef

Dudbridge F (2013) Power and predictive accuracy of polygenic risk scores. PLoS Genet 9(3):e1003348. https://doi.org/10.1371/journal.pgen.1003348CrossRefPubMedPubMedCentral

Duriez Q, Crivello F, Mazoyer B (2014) Sex-related and tissue-specific effects of tobacco smoking on brain atrophy: assessment in a large longitudinal cohort of healthy elderly. Front Aging Neurosci 6:299. https://doi.org/10.3389/fnagi.2014.00299CrossRefPubMedPubMedCentral

Eavani H, Habes M, Satterthwaite TD, An Y, Hsieh MK, Honnorat N, Davatzikos C (2018) Heterogeneity of structural and functional imaging patterns of advanced brain aging revealed via machine learning methods. Neurobiol Aging 71:41–50. https://doi.org/10.1016/j.neurobiolaging.2018.06.013CrossRefPubMedPubMedCentral

Elias MF, Elias PK, D'agostino RB, Silbershatz H, Wolf PA (1997) Role of age, education, and gender on cognitive performance in the Framingham Heart Study: community-based norms. Exp Aging Res 23(3):201–235PubMedCrossRef

Engeroff T, Vogt L, Fleckenstein J, Füzéki E, Matura S, Pilatus U, Pantel J (2019) Lifespan leisure physical activity profile, brain plasticity and cognitive function in old age. Aging Mental health 23(7):811–818PubMedCrossRef

Erickson KI, Colcombe SJ, Elavsky S, McAuley E, Korol DL, Scalf PE, Kramer AF (2007) Interactive effects of fitness and hormone treatment on brain health in postmenopausal women. Neurobiol Aging 28(2):179–185. https://doi.org/10.1016/j.neurobiolaging.2005.11.016CrossRefPubMed

Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kramer AF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci 108(7):3017–3022. https://doi.org/10.1073/pnas.1015950108CrossRefPubMedPubMedCentral

Erickson KI, Leckie RL, Weinstein AM (2014) Physical activity, fitness, and gray matter volume. Neurobiol Aging 35:S20-28. https://doi.org/10.1016/j.neurobiolaging.2014.03.034CrossRefPubMed

Faul F, Erdfelder E, Buchner A, Lang AG (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41(4):1149–1160. https://doi.org/10.3758/BRM.41.4.1149CrossRefPubMed

Feduccia AA, Chatterjee S, Bartlett SE (2012) Neuronal nicotinic acetylcholine receptors: neuroplastic changes underlying alcohol and nicotine addictions. Front Mol Neurosci 5:83. https://doi.org/10.3389/fnmol.2012.00083CrossRefPubMedPubMedCentral

Fjell AM, Walhovd KB (2010) Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neurosci 21(3):187–222PubMedCrossRef

Floel A, Witte AV, Lohmann H, Wersching H, Ringelstein EB, Berger K, Knecht S (2008) Lifestyle and memory in the elderly. Neuroepidemiology 31(1):39–47. https://doi.org/10.1159/000137378CrossRefPubMed

Floel A, Ruscheweyh R, Kruger K, Willemer C, Winter B, Volker K, Knecht S (2010) Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link? Neuroimage 49(3):2756–2763. https://doi.org/10.1016/j.neuroimage.2009.10.043CrossRefPubMed

Franke GH, Bullinger M, Kirchberger I (1998) SF-36. Fragebogen zum Gesundheitszustand. Handanweisung. Göttingen: Hogrefe. Z Med Psy 7:190–191

Franke K, Ziegler G, Kloppel S, Gaser C, ADNI (2010) Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: Exploring the influence of various parameters. Neuroimage 50(3):883–892. https://doi.org/10.1016/j.neuroimage.2010.01.005CrossRefPubMed

Franke K, Gaser C, ADNI (2012) Longitudinal changes in individual BrainAGE in healthy aging, mild cognitive impairment, and Alzheimer’s Disease. GeroPsych 25(4):235–245. https://doi.org/10.1024/1662-9647/a000074CrossRef

Franke K, Ristow M, Gaser C, Alzheimer’s Disease Neuroimaging, I (2014) Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects. Front Aging Neurosci 6(94):1–14. https://doi.org/10.3389/fnagi.2014.00094CrossRef

Franklin TR, Wetherill RR, Jagannathan K, Johnson B, Mumma J, Hager N, Childress AR (2014) The effects of chronic cigarette smoking on gray matter volume: influence of sex. PLoS ONE 9(8):e104102. https://doi.org/10.1371/journal.pone.0104102CrossRefPubMedPubMedCentral

Fratiglioni L, Paillard-Borg S, Winblad B (2004) An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol 3(6):343–353. https://doi.org/10.1016/s1474-4422(04)00767-7CrossRefPubMed

Freund KM, Belanger AJ, D’Agostino RB, Kannel WB (1993) The health risks of smoking the framingham study: 34 years of follow-up. Ann Epidemiol 3(4):417–424PubMedCrossRef

Gallinat J, Meisenzahl E, Jacobsen LK, Kalus P, Bierbrauer J, Kienast T, Staedtgen M (2006) Smoking and structural brain deficits: a volumetric MR investigation. Eur J Neurosci 24(6):1744–1750. https://doi.org/10.1111/j.1460-9568.2006.05050.xCrossRefPubMed

Garcia-Segura LM, Cardona-Gómez GP, Chowen JA, Azcoitia I (2000) Insulin-like growth factor-I receptors and estrogen receptors interact in the promotion of neuronal survival and neuroprotection. J Neurocytol 29(5–6):425–437PubMedCrossRef

Gaser C, Franke K, Kloppel S, Koutsouleris N, Sauer H, Alzheimer’s Disease Neuroimaging, I (2013) BrainAGE in mild cognitive impaired patients: predicting the conversion to Alzheimer’s disease. PLoS ONE 8(6):e67346. https://doi.org/10.1371/journal.pone.0067346CrossRefPubMedPubMedCentral

Glovannucci E, Colditz G, Stampfer MJ, Rimm EB, Litin L, Sampson L, Willett WC (1991) The assessment of alcohol consumption by a simple self-administered questionnaire. Am J Epidemiol 133(8):810–817CrossRef

Gons RA, van Norden AG, de Laat KF, van Oudheusden LJ, van Uden IW, Zwiers MP, de Leeuw FE (2011) Cigarette smoking is associated with reduced microstructural integrity of cerebral white matter. Brain 134(Pt 7):2116–2124. https://doi.org/10.1093/brain/awr145CrossRefPubMed

Gow AJ, Bastin ME, Maniega SM, Hernández MCV, Morris Z, Murray C, Wardlaw JM (2012) Neuroprotective lifestyles and the aging brain: activity, atrophy, and white matter integrity. Neurology 79(17):1802–1808PubMedCrossRef

Gur RC, Gur RE (2017) Complementarity of sex differences in brain and behavior: from laterality to multimodal neuroimaging. J Neurosci Res 95(1–2):189–199. https://doi.org/10.1002/jnr.23830CrossRefPubMedPubMedCentral

Hafsteinsdottir SH, Eiriksdottir G, Sigurdsson S, Aspelund T, Harris TB, Launer LJ, Gudnason V (2012) Brain tissue volumes by APOE genotype and leisure activity—the AGES-Reykjavik Study. Neurobiol Aging 33(4):829.e821-829.e828. https://doi.org/10.1016/j.neurobiolaging.2011.06.028CrossRef

Harrison TM, Mahmood Z, Lau EP, Karacozoff AM, Burggren AC, Small GW, Bookheimer SY (2016) An Alzheimer’s disease genetic risk score predicts longitudinal thinning of hippocampal complex subregions in healthy older adults. eNeuro 3(3):1–13. https://doi.org/10.1523/eneuro.0098-16.2016CrossRef

Hayes SM, Hayes JP, Cadden M, Verfaellie M (2013) A review of cardiorespiratory fitness-related neuroplasticity in the aging brain. Front Aging Neurosci 5:1–16. https://doi.org/10.3389/fnagi.2013.00031CrossRef

Ho AJ, Raji CA, Becker JT, Lopez OL, Kuller LH, Hua X, Thompson PM (2011) The effects of physical activity, education, and body mass index on the aging brain. Hum Brain Mapp 32(9):1371–1382. https://doi.org/10.1002/hbm.21113CrossRefPubMed

Howard G, Wagenknecht LE, Cai J, Cooper L, Kraut MA, Toole JF (1998) Cigarette smoking and other risk factors for silent cerebral infarction in the general population. Stroke 29(5):913–917PubMedCrossRef

Hughes TF, Ganguli M (2009) Modifiable midlife risk factors for late-life cognitive impairment and dementia. Curr Psychiatry Rev 5(2):73–92PubMedPubMedCentralCrossRef

Jagust W (2013) Vulnerable neural systems and the borderland of brain aging and neurodegeneration. Neuron 77(2):219–234. https://doi.org/10.1016/j.neuron.2013.01.002CrossRefPubMedPubMedCentral

James BD, Glass TA, Caffo B, Bobb JF, Davatzikos C, Yousem D, Schwartz BS (2012) Association of social engagement with brain volumes assessed by structural MRI. J Aging Res 2012:512714. https://doi.org/10.1155/2012/512714CrossRefPubMedPubMedCentral

Janes AC, Nickerson LD, Frederick Bde B, Kaufman MJ (2012) Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls. Drug Alcohol Depend 125(3):252–259. https://doi.org/10.1016/j.drugalcdep.2012.02.020CrossRefPubMedPubMedCentral

Jiang R, Calhoun VD, Fan L, Zuo N, Jung R, Qi S, Song M (2020) Gender differences in connectome-based predictions of individualized intelligence quotient and sub-domain scores. Cereb Cortex 30(3):888–900PubMedCrossRef

Jockwitz C, Caspers S, Lux S, Jutten K, Schleicher A, Eickhoff SB, Zilles K (2017) Age- and function-related regional changes in cortical folding of the default mode network in older adults. Brain Struct Funct 222(1):83–99. https://doi.org/10.1007/s00429-016-1202-4CrossRefPubMed

Jockwitz C, Merillat S, Liem F, Oschwald J, Amunts K, Caspers S, Jancke L (2019) Generalizing age effects on brain structure and cognition: a two-study comparison approach. Hum Brain Mapp. https://doi.org/10.1002/hbm.24524CrossRefPubMedPubMedCentral

Jónsson BA, Bjornsdottir G, Thorgeirsson T, Ellingsen LM, Walters GB, Gudbjartsson D, Ulfarsson M (2019) Brain age prediction using deep learning uncovers associated sequence variants. Nat Commun 10(1):1–10CrossRef

Karama S, Ducharme S, Corley J, Chouinard-Decorte F, Starr JM, Wardlaw JM, Deary IJ (2015) Cigarette smoking and thinning of the brain’s cortex. Mol Psychiatry 20(6):778–785. https://doi.org/10.1038/mp.2014.187CrossRefPubMedPubMedCentral

Kalbe E, Kessler J, Calabrese P, Smith R, Passmore AP, Brand MA, Bullock R (2004) DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia. Int J Geriatr psychiatry 19(2):136–143PubMedCrossRef

Kaufmann T, van der Meer D, Doan NT, Schwarz E, Lund MJ, Agartz I, Bertolino A (2019) Common brain disorders are associated with heritable patterns of apparent aging of the brain. Nat Neurosci 22(10):1617–1623PubMedPubMedCentralCrossRef

Kiesow H, Dunbar R, Kable J, Kalenscher T, Vogeley K, Schilbach L, Bzdok D (2020) 10,000 social brains: sex differentiation in human brain anatomy. Sci Adv 6(12):1170CrossRef

Kramer AF, Colcombe S (2018) Fitness effects on the cognitive function of older adults: a meta-analytic study—revisited. Perspect Psychol Sci 13(2):213–217PubMedCrossRef

Kramer AF, Erickson KI (2007) Capitalizing on cortical plasticity: Influence of physical activity on cognition and brain function. Trends Cogn Sci 11(8):342–348. https://doi.org/10.1016/j.tics.2007.06.009CrossRefPubMed

Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Colcombe A (1999) Ageing, fitness and neurocognitive function. Nature 400(6743):418PubMedCrossRef

Kramer AF, Colcombe SJ, McAuley E, Eriksen KI, Scalf P, Jerome GJ, Webb AG (2003) Enhancing brain and cognitive function of older adults through fitness training. J Mol Neurosci 20(3):213–221PubMedCrossRef

Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36(3):539–548PubMedCrossRef

Longstreth WT, Arnold AM, Beauchamp NJ, Manolio TA, Lefkowitz D, Jungreis C, Furberg CD (2005) Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly. Stroke 36(1):56–61. https://doi.org/10.1161/01.Str.0000149625.99732.69CrossRefPubMed

Lowe LC, Gaser C, Franke K, Neuroimaging AD, I. (2016) The effect of the APOE genotype on individual BrainAGE in normal aging, mild cognitive impairment, and Alzheimer’s disease. PLoS ONE 11(7):e0157514. https://doi.org/10.1371/journal.pone.0157514CrossRefPubMedPubMedCentral

McDonough IM, Allen RS (2019) Biological markers of aging and mental health: a seed and soil model of neurocognitive disorders. Taylor & Francis, New York

McKenna H, Slater P, McCance T, Bunting B, Spiers A, McElwee G (2003) The role of stress, peer influence and education levels on the smoking behaviour of nurses. Int J Nurs Stud 40(4):359–366. https://doi.org/10.1016/s0020-7489(02)00099-8CrossRefPubMed

Milanovic Z, Pantelic S, Trajkovic N, Sporis G, Kostic R, James N (2013) Age-related decrease in physical activity and functional fitness among elderly men and women. Clin Interv Aging 8:549–556. https://doi.org/10.2147/CIA.S44112CrossRefPubMedPubMedCentral

Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, Smith SM (2016) Multimodal population brain imaging in the UK Biobank prospective epidemiological study. Nat Neurosci 19(11):1523–1536. https://doi.org/10.1038/nn.4393CrossRefPubMedPubMedCentral

Mucha L, Stephenson J, Morandi N, Dirani R (2006) Meta-analysis of disease risk associated with smoking, by gender and intensity of smoking. Gend Med 3(4):279–291PubMedCrossRef

Mukamal KJ, Longstreth WT Jr, Mittleman MA, Crum RM, Siscovick DS (2001) Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study. Stroke 32(9):1939–1946PubMedCrossRef

Mukhin AG, Kimes AS, Chefer SI, Matochik JA, Contoreggi CS, Horti AG, Stein EA (2008) Greater nicotinic acetylcholine receptor density in smokers than in nonsmokers: a PET study with 2–18F-FA-85380. J Nucl Med 49(10):1628–1635. https://doi.org/10.2967/jnumed.108.050716CrossRefPubMed

Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW (1996) Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 726:49–56PubMedCrossRef

Ning K, Zhao L, Matloff W, Sun F, Toga AW (2020) Association of relative brain age with tobacco smoking, alcohol consumption, and genetic variants. Sci Rep 10(1):1–10CrossRef

Pariyadath V, Stein EA, Ross TJ (2014) Machine learning classification of resting state functional connectivity predicts smoking status. Front Hum Neurosci 8:425. https://doi.org/10.3389/fnhum.2014.00425CrossRefPubMedPubMedCentral

Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, DeCarli C, Wolf PA (2008) Association of alcohol consumption with brain volume in the Framingham study. Arch Neurol 65(10):1363–1367PubMedPubMedCentralCrossRef

Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK, Rosenbloom MJ, Lim KO (1995) Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res 19(5):1177–1191PubMedCrossRef

Piepmeier AT, Etnier JL (2015) Brain-derived neurotrophic factor (BDNF) as a potential mechanism of the effects of acute exercise on cognitive performance. J Sport Health Sci 4(1):14–23. https://doi.org/10.1016/j.jshs.2014.11.001CrossRef

Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Rock CL (2007) Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 25(17):2345PubMedCrossRef

Prescott E, Osler M, Anderson PK, Hein HO, Borch-Johnsen K, Lange P, Vestbo J (1998) Mortality in women and men in relation to smoking. Int J Epidemiol 27(1):27–32PubMedCrossRef

Pujades-Rodriguez M, George J, Shah AD, Rapsomaniki E, Denaxas S, West R, Hemingway H (2015) Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1937360 people in England: lifetime risks and implications for risk prediction. Int J Epidemiol 44(1):129–141. https://doi.org/10.1093/ije/dyu218CrossRefPubMed

Rajapakse JC, Giedd JN, Rapoport JL (1997) Statistical approach to segmentation of single-channel cerebral MR images. IEEE Trans Med Imaging 16(2):176–186PubMedCrossRef

Ritchie SJ, Cox SR, Shen X, Lombardo MV, Reus LM, Alloza C, Deary IJ (2018) Sex differences in the adult human brain: evidence from 5216 UK Biobank participants. Cereb Cortex 28(8):2959–2975. https://doi.org/10.1093/cercor/bhy109CrossRefPubMedPubMedCentral

Ruigrok AN, Salimi-Khorshidi G, Lai MC, Baron-Cohen S, Lombardo MV, Tait RJ, Suckling J (2014) A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev 39:34–50. https://doi.org/10.1016/j.neubiorev.2013.12.004CrossRefPubMedPubMedCentral

Ruscheweyh R, Willemer C, Krüger K, Duning T, Warnecke T, Sommer J, Flöel A (2011) Physical activity and memory functions: an interventional study. Neurobiol Aging 32(7):1304–1319PubMedCrossRef

Schmermund A, Möhlenkamp S, Stang A, Grönemeyer D, Seibel R, Hirche H, Erbel R (2002) Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Am Heart J 144(2):212–218. https://doi.org/10.1067/mhj.2002.123579CrossRefPubMed

Schölkopf B, Smola AJ, Bach F (2002) Learning with kernels: support vector machines, regularization, optimization, and beyond. MIT press

Shors TJ (2014) The adult brain makes new neurons, and effortful learning keeps them alive. Curr Dir Psychol Sci 23(5):311–318CrossRef

Simons JS, Wills TA, Emery NN, Marks RM (2015) Quantifying alcohol consumption: self-report, transdermal assessment, and prediction of dependence symptoms. Addict Behav 50:205–212. https://doi.org/10.1016/j.addbeh.2015.06.042CrossRefPubMedPubMedCentral

Smith SM, Vidaurre D, Alfaro-Almagro F, Nichols TE, Miller KL (2019) Estimation of brain age delta from brain imaging. Neuroimage 200:528–539PubMedCrossRef

Smith SM, Elliott LT, Alfaro-Almagro F, McCarthy P, Nichols TE, Douaud G, Miller KL (2020) Brain aging comprises many modes of structural and functional change with distinct genetic and biophysical associations. Elife 9:e52677PubMedPubMedCentralCrossRef

Stern Y (2009) Cognitive reserve. Neuropsychologia 47(10):2015–2028. https://doi.org/10.1016/j.neuropsychologia.2009.03.004CrossRefPubMedPubMedCentral

Stern Y (2012) Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol 11(11):1006–1012. https://doi.org/10.1016/s1474-4422(12)70191-6CrossRefPubMedPubMedCentral

Stern Y (2017) An approach to studying the neural correlates of reserve. Brain Imaging Behav 11(2):410–416. https://doi.org/10.1007/s11682-016-9566-xCrossRefPubMedPubMedCentral

Swan GE, Lessov-Schlaggar CN (2007) The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev 17(3):259–273. https://doi.org/10.1007/s11065-007-9035-9CrossRefPubMed

Tanabe J, Nyberg E, Martin LF, Martin J, Cordes D, Kronberg E, Tregellas JR (2011) Nicotine effects on default mode network during resting state. Psychopharmacology 216(2):287–295. https://doi.org/10.1007/s00213-011-2221-8CrossRefPubMedPubMedCentral

Tipping (2001) Sparse Bayesian learning and the relevance vector machine. J Mach Learn Res 1:211–244

Tohka J, Zijdenbos A, Evans A (2004) Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 23(1):84–97. https://doi.org/10.1016/j.neuroimage.2004.05.007CrossRefPubMed

Topiwala A, Allan CL, Valkanova V, Zsoldos E, Filippini N, Sexton C, Ebmeier KP (2017) Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ 357:j2353. https://doi.org/10.1136/bmj.j2353CrossRefPubMedPubMedCentral

Torkamani A, Wineinger NE, Topol EJ (2018) The personal and clinical utility of polygenic risk scores. Nat Rev Genet 19(9):581–590. https://doi.org/10.1038/s41576-018-0018-xCrossRefPubMed

UNESCO (1997) International Standard Classification of Education, ISCED. Advances in cross-national comparison: a european working book for demographic and socio-economic variables, 195–220

Ursini G, Punzi G, Chen Q, Marenco S, Robinson JF, Porcelli A, Weinberger DR (2018) Convergence of placenta biology and genetic risk for schizophrenia. Nat Med 24(6):792–801. https://doi.org/10.1038/s41591-018-0021-yCrossRefPubMed

Van der Maaten LJP (2007) An introduction to dimensionality reduction using matlab. Report, 1201(07-07)

Van Essen DC, Smith SM, Barch DM, Behrens TE, Yacoub E, Ugurbil K, Consortium WU-MH (2013) The WU-Minn Human Connectome Project: an overview. Neuroimage 80:62–79. https://doi.org/10.1016/j.neuroimage.2013.05.041CrossRefPubMed

Varikuti DP, Genon S, Sotiras A, Schwender H, Hoffstaedter F, Patil KR, Amunts K (2018) Evaluation of non-negative matrix factorization of grey matter in age prediction. Neuroimage 173:394–410PubMedCrossRef

Vaughan L, Erickson KI, Espeland MA, Smith JC, Tindle HA, Rapp SR (2014) Concurrent and longitudinal relationships between cognitive activity, cognitive performance, and brain volume in older adult women. J Gerontol B Psychol Sci Soc Sci 69(6):826–836. https://doi.org/10.1093/geronb/gbu109CrossRefPubMedPubMedCentral

Vaynman, S., & Gomez-Pinilla, F. (2005). License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair, 19(4), 283-295. doi:https://doi.org/10.1177/1545968305280753

Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20(10):2580–2590. https://doi.org/10.1111/j.1460-9568.2004.03720.xCrossRefPubMed

Venezia AC, Guth LM, Sapp RM, Spangenburg EE, Roth SM (2016) Sex-dependent and independent effects of long-term voluntary wheel running on Bdnf mRNA and protein expression. Physiol Behav 156:8–15. https://doi.org/10.1016/j.physbeh.2015.12.026CrossRefPubMedPubMedCentral

Vergara VM, Liu J, Claus ED, Hutchison K, Calhoun V (2017) Alterations of resting state functional network connectivity in the brain of nicotine and alcohol users. Neuroimage 151:45–54. https://doi.org/10.1016/j.neuroimage.2016.11.012CrossRefPubMed

Voelcker-Rehage C, Godde B, Staudinger UM (2010) Physical and motor fitness are both related to cognition in old age. Eur J Neurosci 31(1):167–176. https://doi.org/10.1111/j.1460-9568.2009.07014.xCrossRefPubMed

Voelcker-Rehage C, Godde B, Staudinger UM (2011) Cardiovascular and coordination training differentially improve cognitive performance and neural processing in older adults. Front Human Neurosci 5:26. https://doi.org/10.3389/fnhum.2011.00026CrossRef

Wagner A, Dallongeville J, Haas B, Ruidavets JB, Amouyel P, Ferrieres J, Arveiler D (2012) Sedentary behaviour, physical activity and dietary patterns are independently associated with the metabolic syndrome. Diabetes Metab 38(5):428–435. https://doi.org/10.1016/j.diabet.2012.04.005CrossRefPubMed

Wierenga LM, Sexton JA, Laake P, Giedd JN, Tamnes CK, Pediatric Imaging N, Genetics S (2018) A key characteristic of sex differences in the developing brain: greater variability in brain structure of boys than girls. Cereb Cortex 28(8):2741–2751. https://doi.org/10.1093/cercor/bhx154CrossRefPubMed

WHO (2019) Global action plan on physical activity 2018–2030: more active people for a healthier world. World Health Organization, Geneve

Wu BN, O’Sullivan AJ (2011) Sex differences in energy metabolism need to be considered with lifestyle modifications in humans. J Nutr Metab 2011:391809. https://doi.org/10.1155/2011/391809CrossRefPubMedPubMedCentral

Yarkoni T, Westfall J (2017) Choosing prediction over explanation in psychology: lessons from machine learning. Perspect Psychol Sci 12(6):1100–1122PubMedPubMedCentralCrossRef

Zhou S, Xiao D, Peng P, Wang SK, Liu Z, Qin HY, Wang C (2017) Effect of smoking on resting-state functional connectivity in smokers: an fMRI study. Respirology 22(6):1118–1124PubMedCrossRef

Ziegler G, Dahnke R, Gaser C, ADNI (2012) Models of the aging brain structure and individual decline. Front Neuroinform 6:1–13. https://doi.org/10.3389/fninf.2012.00003CrossRef

Title: When your brain looks older than expected: combined lifestyle risk and BrainAGE
Authors: Nora Bittner
Christiane Jockwitz
Katja Franke
Christian Gaser
Susanne Moebus
Ute J. Bayen
Katrin Amunts
Svenja Caspers
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 3/2021
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-020-02184-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

When your brain looks older than expected: combined lifestyle risk and BrainAGE

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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