Allostatic load as a predictor of grey matter volume and white matter integrity in old age: The Whitehall II MRI study

The allostatic load index quantifies the cumulative multisystem physiological response to chronic everyday stress, and includes cardiovascular, metabolic and inflammatory measures. Despite its central role in the stress response, research of the effect of allostatic load on the ageing brain has been limited. We investigated the relation of mid-life allostatic load index and multifactorial predictors of stroke (Framingham stroke risk) and diabetes (metabolic syndrome) with voxelwise structural grey and white matter brain integrity measures in the ageing Whitehall II cohort (N = 349, mean age = 69.6 (SD 5.2) years, N (male) = 281 (80.5%), mean follow-up before scan = 21.4 (SD 0.82) years). Higher levels of all three markers were significantly associated with lower grey matter density. Only higher Framingham stroke risk was significantly associated with lower white matter integrity (low fractional anisotropy and high mean diffusivity). Our findings provide some empirical support for the concept of allostatic load, linking the effect of everyday stress on the body with features of the ageing human brain.

[1]  R. Stewart,et al.  Vascular Risk Factors and Alzheimer's Disease , 1999, The Australian and New Zealand journal of psychiatry.

[2]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[3]  Klaus P. Ebmeier,et al.  Study protocol: the Whitehall II imaging sub-study , 2014, BMC Psychiatry.

[4]  G. Tseng,et al.  Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology. , 2016, Journal of psychiatric research.

[5]  J M Wardlaw,et al.  Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study: the Rotterdam Scan Study , 2001, Journal of neurology, neurosurgery, and psychiatry.

[6]  R. Buckner,et al.  Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD , 2005, Neurology.

[7]  Regional cortical thickness and subcortical volume changes in patients with metabolic syndrome , 2015, Brain Imaging and Behavior.

[8]  Stuart J. Ritchie,et al.  Edinburgh Research Explorer Association of allostatic load with brain structure and cognitive ability in later life , 2022 .

[9]  J. Mattei,et al.  Allostatic load and the assessment of cumulative biological risk in biobehavioral medicine: challenges and opportunities. , 2014, Psychosomatic medicine.

[10]  A. Convit,et al.  Impact of metabolic syndrome on cognition and brain: a selected review of the literature. , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[11]  J W Rowe,et al.  Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C. DeCarli,et al.  Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline , 2011, Alzheimer's & Dementia.

[13]  E. Epel.  Psychological and metabolic stress: A recipe for accelerated cellular aging? , 2009, Hormones.

[14]  F. Telang,et al.  Risk factors for white matter changes detected by magnetic resonance imaging in the elderly. , 1990, Stroke.

[15]  Wiro J. Niessen,et al.  Tract-specific white matter degeneration in aging: The Rotterdam Study , 2015, Alzheimer's & Dementia.

[16]  H. Markus,et al.  The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis , 2010, BMJ : British Medical Journal.

[17]  E. Grundy,et al.  Allostatic Load and Health in the Older Population of England: A Crossed-Lagged Analysis , 2014, Psychosomatic medicine.

[18]  N. Goldman,et al.  Physiological dysregulation and changes in health in an older population , 2006, Experimental Gerontology.

[19]  W. Markesbery,et al.  Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. , 1997, JAMA.

[20]  B. McEwen.  Protective and damaging effects of stress mediators: central role of the brain , 2006, Dialogues in clinical neuroscience.

[21]  Cyrus Martin,et al.  What is stress? , 2014, Current Biology.

[22]  Sandra E. Black,et al.  Vascular cognitive impairment , 2018, Nature Reviews Disease Primers.

[23]  J. Bogousslavsky,et al.  Large infarcts in the middle cerebral artery territory Etiology and outcome patterns , 1998, Neurology.

[24]  N. Unwin,et al.  Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Detection, Evaluation, and Treatment of High Blood Cholesterol Education Program (NCEP) Expert Panel on Executive Summary of the Third Report of the National , 2009 .

[25]  Michael Marmot,et al.  Cohort Profile: the Whitehall II study. , 2005, International journal of epidemiology.

[26]  P. Kochunov,et al.  Fornix Structural Connectivity and Allostatic Load: Empirical Evidence From Schizophrenia Patients and Healthy Controls , 2017, Psychosomatic medicine.

[27]  Klaus P. Ebmeier,et al.  Vascular Risk Status as a Predictor of Later-Life Depressive Symptoms: A Cohort Study , 2012, Biological Psychiatry.

[28]  W. Hacke,et al.  'Malignant' middle cerebral artery territory infarction : Clinical course and prognostic signs , 1996 .

[29]  J. Garcìa,et al.  Cerebral white matter is highly vulnerable to ischemia. , 1996, Stroke.

[30]  B. McEwen,et al.  Allostatic load biomarkers of chronic stress and impact on health and cognition , 2010, Neuroscience & Biobehavioral Reviews.

[31]  K. Rockwood,et al.  Vascular cognitive impairment: current concepts and clinical developments , 2008, The Lancet Neurology.

[32]  A. Steptoe,et al.  Physical Activity, Sedentary Time, and Pericardial Fat in Healthy Older Adults , 2012, Obesity.

[33]  T. Seeman,et al.  Protective and Damaging Effects of Mediators of Stress: Elaborating and Testing the Concepts of Allostasis and Allostatic Load , 1999, Annals of the New York Academy of Sciences.

[34]  N. H. Rod,et al.  Work Stress, Caregiving, and Allostatic Load: Prospective Results From the Whitehall II Cohort Study , 2015, Psychosomatic medicine.

[35]  Sudha Seshadri,et al.  Association of MRI Markers of Vascular Brain Injury With Incident Stroke, Mild Cognitive Impairment, Dementia, and Mortality: The Framingham Offspring Study , 2010, Stroke.

[36]  E. Cadenas,et al.  Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain , 2007 .

[37]  L. Peng,et al.  Predicting all-cause and cause-specific mortality by static and dynamic measurements of allostatic load: a 10-year population-based cohort study in Taiwan. , 2014, Journal of the American Medical Directors Association.

[38]  W. M. van der Flier,et al.  On the Etiology of Incident Brain Lacunes: Longitudinal Observations From the LADIS Study , 2008, Stroke.

[39]  H. Savolainen,et al.  HOW DID STROKE BECOME OF INTEREST TO NEUROLOGISTS? A SLOW 19TH CENTURY SAGA , 2009, Neurology.

[40]  W. Markesbery,et al.  Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS☆ , 2000, Neurobiology of Aging.

[41]  Burton H Singer,et al.  Reduction in Allostatic Load in Older Adults Is Associated With Lower All-Cause Mortality Risk: MacArthur Studies of Successful Aging , 2006, Psychosomatic medicine.

[42]  Stephen M. Smith,et al.  Permutation inference for the general linear model , 2014, NeuroImage.

[43]  F. Seguin,et al.  Effects of stress throughout the lifespan on the brain, behaviour and cognition , 2009 .

[44]  P. Kochunov,et al.  Allostatic load and reduced cortical thickness in schizophrenia , 2017, Psychoneuroendocrinology.

[45]  Y. Yang,et al.  Sex differences in age trajectories of physiological dysregulation: inflammation, metabolic syndrome, and allostatic load. , 2011, The journals of gerontology. Series A, Biological sciences and medical sciences.

[46]  Gower Street,et al.  Health inequalities among British civil servants: the Whitehall II study , 1991, The Lancet.

[47]  T. Seeman,et al.  Age differences in allostatic load: an index of physiological dysregulation , 2003, Experimental Gerontology.

[48]  S. Schwab,et al.  Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives , 2009, The Lancet Neurology.

[49]  J. Trojanowski,et al.  Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. , 2013, Brain : a journal of neurology.

[50]  A. Hofman,et al.  Incidence and risk of dementia. The Rotterdam Study. , 1998, American journal of epidemiology.

[51]  Joanna M. Wardlaw,et al.  Risk and protective factors for structural brain ageing in the eighth decade of life , 2017, Brain Structure and Function.

[52]  D. Norris,et al.  Hypertension is related to the microstructure of the corpus callosum: the RUN DMC study. , 2012, Journal of Alzheimer's disease : JAD.

[53]  J. Szaflarski,et al.  Ischemic Stroke Subtypes: A Population-Based Study of Incidence Rates Among Blacks and Whites , 2004, Stroke.

[54]  Bruce McEwen,et al.  Gender differences in age-related changes in HPA axis reactivity , 2001, Psychoneuroendocrinology.

[55]  M. Kemeny,et al.  Subjective social status moderates cortisol responses to social threat , 2006, Brain, Behavior, and Immunity.

[56]  R B D'Agostino,et al.  Stroke risk profile: adjustment for antihypertensive medication. The Framingham Study. , 1994, Stroke.

[57]  J. Wingfield,et al.  The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade-offs in health and disease , 2005, Neuroscience & Biobehavioral Reviews.

[58]  Trevor A. Day,et al.  Defining stress as a prelude to mapping its neurocircuitry: No help from allostasis , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[59]  Klaus P. Ebmeier,et al.  Does the Framingham Stroke Risk Profile predict white-matter changes in late-life depression? , 2011, International Psychogeriatrics.

[60]  M. Weden,et al.  Historical and life course timing of the male mortality disadvantage in Europe: Epidemiologic transitions, evolution, and behavior , 2006, Social biology.

[61]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[62]  Mika Kivimäki,et al.  Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study , 2009, The Lancet.

[63]  Meena Kumari,et al.  Work stress and coronary heart disease: what are the mechanisms? , 2008, European heart journal.

[64]  M. Marmot,et al.  Social inequality in coronary risk: Central obesity and the metabolic syndrome. Evidence from the Whitehall II study , 1997, Diabetologia.

[65]  Peter J Gianaros,et al.  Annals of the New York Academy of Sciences Central Role of the Brain in Stress and Adaptation: Links to Socioeconomic Status, Health, and Disease , 2022 .

[66]  Nathan D. Wong,et al.  Impact of the Metabolic Syndrome on Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in United States Adults , 2004, Circulation.

[67]  R. Carare,et al.  Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease , 2009, Alzheimer's Research & Therapy.

[68]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[69]  Klaus P. Ebmeier,et al.  Aging and Psychological Stress , 2016 .

[70]  Christian Gaser,et al.  Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects , 2014, Front. Aging Neurosci..

[71]  B. Singer,et al.  Price of adaptation--allostatic load and its health consequences. MacArthur studies of successful aging. , 1997, Archives of internal medicine.

[72]  G C Roman,et al.  Brain infarction and the clinical expression of Alzheimer disease. , 1997, JAMA.