Normal aging leads to widespread structural, biochemical, and functional changes in the brain, including brain atrophy, loss of gray and white matter, synaptic and neuronal decline, altered neurotransmitter levels, and changes in cognitive abilities.
Brain aging is a multifactorial process involving atrophy, microstructural and metabolic changes, and mild cognitive decline, with significant inter-individual variability and overlap with early neurodegenerative changes.
Brain aging is characterized by decreased brain volume, especially in the frontal and temporal cortices, expansion of the ventricles, and thinning of the cerebral cortex.
Brain age changes are most pronounced in the prefrontal and temporal regions, with annual reductions in volume of 0.5–1% in most areas.
White matter also shows atrophy and increased hyperintensities, particularly in the frontal lobes, which are linked to cognitive decline and increased risk of stroke and dementia.
At the cellular level, there is loss of neurons and synapses, shrinkage of neuronal cell bodies, and reduced synaptic density, rather than massive neuronal death.
Brain aging also increases oxidative stress, neuroinflammation, and accumulation of age-related pigments such as lipofuscin, as well as mild increases in amyloid and tau pathology, though these are much less extensive than in neurodegenerative diseases.
Aging brains show decreased N-acetyl-aspartate (NAA) (a marker of neuronal integrity) and increased markers of glial activity and altered energy metabolism, such as choline, creatine, and myo-inositol.
Mitochondrial and autophagic changes are also observed, reflecting adaptive and degenerative processes.
Cognitive changes include declines in processing speed, attention, especially divided attention, working memory, episodic memory, and executive function, while semantic memory, vocabulary, and procedural memory are relatively preserved.
These cognitive changes are closely linked to the underlying structural and biochemical alterations.
Brain aging is a multifactorial process involving atrophy, microstructural and metabolic changes, and mild cognitive decline, with significant inter-individual variability and overlap with early neurodegenerative changes.