Ageing and the Brain

Abstract

Anatomical, neurochemical and functional properties of the mammalian brain change with age, and the trajectories of ageing are modified by many genetic and environmental risk factors, including lifestyle variables. Age‐related changes do not reflect a specific cellular program, but fundamental changes precipitating intracellular accumulation of reactive oxygen species and diminishing energy production may underlie age‐related deterioration of the brain structure and information processing properties. The latter has been hypothesised to bring about differential declines in cognitive functions that rely on processing of information of high novelty and low redundancy. These hypotheses are summarised in a Free‐Radical‐Induced Energetic and Neural Declines in Senescence (FRIENDS) model, some components of which have been demonstrated in longitudinal studies, while others can be inferred from cross‐sectional and postmortem investigations. The major obstacle to understanding brain ageing and its role in cognitive change remains the dearth of multi‐occasion longitudinal studies of the relevant constructs. Key Concepts Brain is a disproportional consumer of energy, which is necessary for maintaining its information processing machinery. Energy crisis originating in mitochondrial dysfunction and causing further deterioration of the cellular machinery unfolds in time and thus promotes brain ageing. Decline in metabolic, and vascular properties of the brain is precipitated by energy deficit and drives declines in multiple brain properties. Brain shrinks with age, with key regions implicated in cognitive processing evidencing faster declines in comparison to sensory cortices. Energy intensive functions, such as myelin maintenance and synaptogenesis, may be particularly vulnerable to ageing. Age‐related declines are accelerated by genetic variants linked to vascular disease and inflammation as well as environmental pollution, stress and sedentary lifestyle. Changes in iron homeostasis may precipitate structural brain changes. When individual differences in age‐related cognitive changes are observed, they are coupled with alterations in brain structure and function. Age‐related brain deterioration appears less pronounced in persons with high baseline cognitive performance. Boosting cognitive performance and promoting active lifestyle as well as combatting pro‐inflammatory and metabolic risk factors may help to improve brain maintenance and mitigate age‐related declines.

DNA damage‐associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia

“…The natural history of myelination across the human lifespan closely tracks cognitive capacity [6, 7]. Cortical myelin, in particular in frontal lobes, does not fully mature in humans until their late-thirties [8, 9]. Afterwards myelination regresses and this naturally occurring age-related loss is accelerated in AD [10].…”

Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults

“…With respect to age-related memory impairments, the hippocampal formation, that is, dentate gyrus (DG), cornu Ammonis (CA) fields, and subiculum, warrants particular attention as it is critically involved in memory processing and is affected early in the progression of Alzheimer's disease (AD). Magnetic resonance imaging (MRI) studies have, for example, shown reductions in total hippocampal volume associated with aging in cognitively healthy individuals ( Raz, 2001 ), while hippocampal atrophy remains one of the supporting diagnostic features of amnestic Mild Cognitive Impairment (aMCI) and AD ( de Flores et al., 2015a ). The next challenge is to distinguish normal age-related hippocampal changes from potential pathological changes related to genetic and lifestyle risk factors of dementia in pre-symptomatic individuals ( Jack et al., 2013 ).…”

Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults

“…With respect to age-related memory impairments, the hippocampal formation, i.e., dentate gyrus, cornu Ammonis (CA) fields, and subiculum, warrants particular attention as it is critically involved in memory processing and is affected early in the progression of Alzheimer’s disease (AD). Magnetic resonance imaging (MRI) studies have, for example, shown reductions in total hippocampal volume associated with aging in cognitively healthy individuals (Raz, 2001), while hippocampal atrophy remains one of the supporting diagnostic features of amnestic Mild Cognitive Impairment (aMCI) and AD (de Flores et al, 2015a). The next challenge is to distinguish normal age-related hippocampal changes from potential pathological changes related to genetic and lifestyle risk factors of dementia in pre-symptomatic individuals (Jack et al, 2013).…”