Differential aging of the brain: Patterns, cognitive correlates and modifiers

doi:10.1016/j.neubiorev.2006.07.001

Neuroscience & Biobehavioral Reviews

Volume 30, Issue 6, 2006, Pages 730-748

https://doi.org/10.1016/j.neubiorev.2006.07.001 Get rights and content

Abstract

Deciphering the secret of successful aging depends on understanding the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood. That task is inseparable from comprehending the workings of the brain, the physical substrate of behavior. In this review, we summarize the extant literature on age-related differences and changes in brain structure, including postmortem and noninvasive magnetic resonance imaging (MRI) studies. Among the latter, we survey the evidence from volumetry, diffusion-tensor imaging, and evaluations of white matter hyperintensities (WMH). Further, we review the attempts to elucidate the mechanisms of age-related structural changes by measuring metabolic markers of aging through magnetic resonance spectroscopy (MRS). We discuss the putative links between the pattern of brain aging and the pattern of cognitive decline and stability. We then present examples of activities and conditions (hypertension, hormone deficiency, aerobic fitness) that may influence the course of normal aging in a positive or negative fashion. Lastly, we speculate on several proposed mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination.

Section snippets

Inroduction

For the gods alone there comes no old age, nay nor even death;
but all other things are confounded by all-mastering time ... (Sophocles, Oedipus at Colonus, 607).

Aging—a biological companion of time—spares no organ or system, and in due course affects everything, from cell to thought. However, the pace of aging varies among individual organisms, organs and systems, and the very existence of such variability merits some measure of hope. If the positive extreme of healthy aging can be made more

Postmortem studies

Postmortem (PM) studies of individuals within the adult age span reveal panoply of age-related differences in brain structure. The gross differences include reduced brain weight and volume, ventriculomegaly and sulcal expansion (Kemper, 1994; Skullerud, 1985). Microscopic studies documented myelin pallor (Kemper, 1994), loss of neuronal bodies in the neocortex (Pakkenberg and Gundersen, 1997), the hippocampus (Simić et al., 1997) and the cerebellum (Ellis, 1920; Nairn et al., 1989), loss of

Regional brain volume, density and cortical thickness

In vivo volumetry of the healthy aging brain has been conducted since the advent of magnetic resonance imaging (MRI) almost 20 years ago. Summarizing the results of these two decades or research is a challenging task, for variability among the studies is significant and not easily interpretable. Nonetheless, a general trend that emerges from this literature (for detailed reviews and tabulation of relevant studies see Raz, 2000, Raz, 2004) suggests that the prefrontal cortices are more

Ventricular system

Cerebral ventricles are not as stable a neuroanatomical structure as the brain parenchyma. The nuclei and white matter tracts that abut them define the volume of the cerebral ventricles, and thus it is a summary index of changes across the whole central nervous system. Global measures of the brain and ventricles can be accomplished with extremely high reliability and high degree of automation and are therefore a natural choice for first (and unfortunately, the only) measure in many

Age-related differences in metabolic markers of neural integrity

In contrast to structural MRI in which frequency information is used to encode location of the signal source in the brain, a direct use of frequency information in combination with the chemical shift phenomenon allows identification of specific chemical compounds within a circumscribed brain region. The latter approach, MRS comes in two basic varieties: proton-based (¹H-MRS) and phosphorus-based (³¹P-MRS), although measurement of other elements, such as carbon and sodium are possible. Most

Structural brain correlates of cognitive aging

Age-related differences in regional brain volumes and integrity of the white matter are associated with cognitive performance. However, reviews of the literature reveal that the magnitude of the observed associations is modest (Raz, 2000; Gunning-Dixon and Raz, 2000). When structure-cognition associations are found, they are not easily replicated and appear sensitive to the sample composition and choice of cognitive measures. To date, evidence of links between smaller volume of the hippocampus

Modifiers of brain aging: the good news and the bad news

Whereas aging is associated with the passage of time, it should not be confused with it. Multiple factors affect brain development and aging and alter the trajectories of individuals and whole species. Some of those modifying factors act as accelerators of age-related declines, while others may slow age-related deterioration and delay attainment of pathological levels. Identifying such factors and gauging their contribution to emergence of the observed pattern of brain aging is crucial to

Mechanisms of differential brain aging

There is no dearth of theories of aging, and some sources put their number at more than 300 (Polla et al., 2003). It is unlikely that one or two basic mechanisms would account for the observed complex pattern of differential aging. However, it is equally unlikely for the changes replicated across multiple studies to reflect a set of random events. Several possible explanations of differential aging can be proposed, with no assumption of their mutual independence or exclusion.

Not all neurons are

Limitations of neuroanatomical techniques

This survey would be incomplete without at least a summary of the limitations that measures of brain structure impose on the investigation of the aging brain. All research approaches have their windows of sensitivity and their limitations that must be explicated if a balanced interpretation of the data is sought. Below, we dwell on some of the major constraints that PM and in vivo neuroanatomy impose on the interpretation of the results.

Conclusions

Drawing on the extant literature reviewed above, we can suggest several tentative conclusions. First, the postmortem and structural neuroimaging literature indicates that the human brain shrinks with age, and brain shrinkage is selective and differential, not uniform or randomly distributed. Through most of the adult lifespan, the tertiary association cortices, the neostriatum, and the cerebellum are more profoundly affected by aging than sensory cortices and the pons. The subcortical white

Acknowledgments

This work was supported in part by National Institute of Health grant AG-11230. The first author gratefully acknowledges the support of Max Planck Institute for Human Development, in which he was a visiting scientist during his work on this article. We are grateful to Mikko P. Laakso and the anonymous reviewers for helpful comments on earlier version of this review.

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ReviewDifferential aging of the brain: Patterns, cognitive correlates and modifiers

Abstract

Section snippets

Inroduction

Postmortem studies

Regional brain volume, density and cortical thickness

Ventricular system

Age-related differences in metabolic markers of neural integrity

Structural brain correlates of cognitive aging

Modifiers of brain aging: the good news and the bad news

Mechanisms of differential brain aging

Limitations of neuroanatomical techniques

Conclusions

Acknowledgments

Neurobiology of Aging

Lancet

Neurobiology of Aging

Lancet Neurology

Neurobiology of Aging

Neurobiology of Aging

Neuroscience Letters

Current Opinion in Cell Biology

Journal of the Neurological Sciences

Neurobiology of Aging

Life Science

NeuroImage

Magnetic Resonance Imaging

Magnetic Resonance Imaging

Neurobiology of Aging

American Journal of Geriatric Psychiatry

Trends in Neurosciences

Psychiatric Research

Neurobiology of Aging

Neurobiology of Aging

Neurobiology of Aging

Neurobiology of Aging

Psychiatry Research-Neuroimaging

Neuron

NeuroImage

Neuropsychologia

NeuroImage

Magnetic Resonance Imaging

Neurobiology of Aging

Neuroscience and Biobehavioral Reviews

Cortex

Age-related changes in fibre composition of the human corpus callosum: sex differences

Neuroreport

Basal ganglia

Effect of long-term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats

Mechanisms of Ageing and Development

Regional differences and metabolic changes in normal aging of the human brain: proton MR spectroscopic imaging study

American Journal of Neuroradiology

Chronic back pain is associated with decreased prefrontal and thalamic gray matter density

Journal of Neuroscience

Neuroanatomical localisation and clinical correlates of white matter lesions in the elderly

Journal of Neurology Neurosurgery and Psychiatry

The role of dopamine systems in cognitive aging

Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study

Psychopharmacology (Berl)

The cholinergic hypothesis: a historical overview, current perspective, and future directions

Annals of the New York Academy of Sciences

Age-related changes in frontal and temporal volume in men: a magnetic resonance imaging study

Archives of General Psychiatry

White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study

Archives of Neurology

The neuropathology of adult HIV infection

Revue Neurologique (Paris)

Localization of the growth-associated phosphoprotein GAP-43 (B-50, F1) in the human cerebral cortex

Journal of Neuroscience

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Annals of the New York Academy of Sciences

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Acta Neuropathologica

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American Journal of Roentgenology

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Cerebral Cortex

Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex

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Review
Differential aging of the brain: Patterns, cognitive correlates and modifiers