Cortical Thinning at Midlife: The PATH Through Life Study

Cortical thinning is a part of normal ageing. Recent studies suggest that accelerated cortical thinning in vulnerable regions may be a useful biomarker for neuropathologies including Alzheimer’s disease (AD). Longitudinal studies, which have largely focused on older adults, have provided estimates of normative rates and patterns of age-related cortical thinning. Very little, however, is known about healthy cortical thinning at midlife. Here we provide longitudinal estimates of age-related cortical thinning observed over 8 years, in a large (n = 404) group of healthy individuals aged 44–49 years at baseline, who were scanned with MRI (1.5T) on up to three occasions. Age-related cortical thinning was assessed across the whole cortex. We measured a mean annual decrease in cortical thickness of 0.26 % on the left and 0.17 % on the right hemisphere, and largely affecting frontal and cingulate cortices. Medial and lateral temporal regions were generally spared. Studying regions that are specifically vulnerable to—or spared from—healthy age-related cortical thinning at midlife may be important for the early identification of neurodegeneration, including AD.

[1]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[2]  Mark E. Schmidt,et al.  The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception , 2012, Alzheimer's & Dementia.

[3]  B. Dickerson,et al.  Age-Related Changes in the Thickness of Cortical Zones in Humans , 2011, Brain Topography.

[4]  R. Gur,et al.  Gender differences in age effect on brain atrophy measured by magnetic resonance imaging. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Nicolas Cherbuin,et al.  A systematic review and meta-analysis of longitudinal hippocampal atrophy in healthy human ageing , 2015, NeuroImage.

[6]  A. Dale,et al.  Regional rates of neocortical atrophy from normal aging to early Alzheimer disease , 2009, Neurology.

[7]  A. Simmons,et al.  Education increases reserve against Alzheimer’s disease—evidence from structural MRI analysis , 2012, Neuroradiology.

[8]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[9]  Nicolas Cherbuin,et al.  Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study , 2016, Neurobiology of Aging.

[10]  Riccardo E. Marioni,et al.  Cognitive function, dementia and type 2 diabetes mellitus in the elderly , 2011, Nature Reviews Endocrinology.

[11]  N. Raz Aging of the brain and its impact on cognitive performance: Integration of structural and functional findings. , 2000 .

[12]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[13]  A. Dale,et al.  Accelerating cortical thinning: unique to dementia or universal in aging? , 2014, Cerebral cortex.

[14]  Alan C. Evans,et al.  Changes in thickness and surface area of the human cortex and their relationship with intelligence. , 2015, Cerebral cortex.

[15]  A. Dale,et al.  Thinning of the cerebral cortex in aging. , 2004, Cerebral cortex.

[16]  A. Dale,et al.  Critical ages in the life course of the adult brain: nonlinear subcortical aging , 2013, Neurobiology of Aging.

[17]  Mert R. Sabuncu,et al.  Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models , 2013, NeuroImage.

[18]  Bruce Fischl,et al.  Within-subject template estimation for unbiased longitudinal image analysis , 2012, NeuroImage.

[19]  A. Dale,et al.  Brain Changes in Older Adults at Very Low Risk for Alzheimer's Disease , 2013, The Journal of Neuroscience.

[20]  Torsten Rohlfing,et al.  Variation in longitudinal trajectories of regional brain volumes of healthy men and women (ages 10 to 85years) measured with atlas-based parcellation of MRI , 2013, NeuroImage.

[21]  L. Westlye,et al.  Differential Longitudinal Changes in Cortical Thickness, Surface Area and Volume across the Adult Life Span: Regions of Accelerating and Decelerating Change , 2014, The Journal of Neuroscience.

[22]  S. Resnick,et al.  Longitudinal pattern of regional brain volume change differentiates normal aging from MCI , 2009, Neurology.

[23]  D. Head,et al.  Differential aging of the medial temporal lobe , 2004, Neurology.

[24]  I. Kohane,et al.  Gene regulation and DNA damage in the ageing human brain , 2004, Nature.

[25]  Aaron Carass,et al.  Longitudinal changes in cortical thickness associated with normal aging , 2010, NeuroImage.

[26]  K. Walhovd,et al.  Structural Brain Changes in Aging: Courses, Causes and Cognitive Consequences , 2010, Reviews in the neurosciences.

[27]  Kaarin J Anstey,et al.  Cohort profile: the PATH through life project. , 2012, International journal of epidemiology.