Overview

• Aging is an inevitable and complex physiological process, that is characterised by progressive decline in structure and function across systems (including the brain), and is associated with a greater vulnerability to diseased states.
• A slow and gradual decline in the number of brain cells is a normal process in aging! An expected rate of annual decline is ~0.5% after age 40.
• The hallmarks of neurodegenerative diseases lead to abnormal rates of atrophy or degeneration, resulting in a constellation of physical and cognitive symptoms. Women are disproportionately more affected by neurological conditions than men, having a higher incidence of stroke, dementia, Alzheimer’s disease, depression and others.
• This might be due to fluctuations in estrogen, particularly after menopause!

The Aging Brain

Aging is an inevitable and complex physiological process, that is characterised by progressive decline in structure and function across systems (including the brain), and is associated with a greater vulnerability to diseased states. Several events occur in the central nervous system as we age, including a reduced capacity for DNA repair, mitochondrial dysfunction, loss of synapses, brain inflammation, cognitive decline, regional alterations in water content, and most notably, atrophy. The most straightforward way of estimating atrophy is by using non-invasive neuroimaging techniques, such as MRI, where volumetric measurements are taken of different brain regions. Evidence suggests that aging of different brain regions is driven by different biological sources (Filo et al., 2019). Changes in water content have been found to be more substantial in the white matter regions of the aging brain, whereas changes in iron content and brain volume have been associated with cortical atrophy (Filo et al., 2019). Substantial chemophysical changes have also been found in the thalamus (Filo et al., 2019), a region associated with the relay of sensory impulses from receptors in various parts of the body to the cerebral cortex. Nevertheless, a slow and gradual decline in the number of brain cells is a normal process in aging! An expected rate of annual decline is ~0.5% after age 40 (Fjell et al., 2009).

Additional broad brain changes in aging

Effects of Aging	Description
Structural Changes	thinning of the cerebral cortex, volumetric reductions of most subcortical structures, expansion of the ventricles.
Changes in Vasculature	reduced lymphatic flow and aging of blood vessels (vasculature) resulting in increased blood pressure, greater risk of stroke, ischemia, and development of white matter lesions.
Cognitive Decline	decline in memory; brain activation becomes more bilateral for memory tasks, slower speed of thinking, lower attentional control

Interesting Fact

“Biological aging is not tied absolutely to chronological aging and it may be possible to slow biological aging and even reduce the possibility of suffering from age related diseases such as dementia.”

Peters (2006)

Neuroprotective Lifestyle Factors

What do Neurodegenerative Disorders Have In Common?

Short answer: an increased rate of atrophy in different brain regions.

Every neurodegenrative condition has its hallmarks, such as the formation of clusters of misfolded proteins (amyloid beta protein) in and around neurons in Alzheimer’s disease, and the formation of Lewy bodies (clumps of the protein alpha-synuclein) in Parkinson’s disease. These ultimately lead to abnormal rates of atrophy or degeneration, resulting in a constellation of physical and cognitive symptoms. Women are disproportionately more affected by neurological conditions than men, having a higher incidence of stroke, dementia, Alzheimer’s disease, depression and others. A popular belief and cause for great scientific curiosity, is that this trend is due to the substantial hormonal changes associated with female reproductive development, particularly the complete depletion of estrogen at menopause. Estrogen has antioxidant properties, exerting important effects in both reproductive and non-reproductive health, especially in the brain. Loss of estrogen is associated with mitochondrial dysfunction, loss of synapses, cognitive decline, inflammation in the brain, and other deleterious functional consequences. It has also been found that loss of estrogen can lead to brain hypometabolism, which is a common neurological feature in postmenopausal women and patients with Alzheimer’s Disease. Research in this area is abundant, however results are quite controversial, particularly regarding the effects of hormone replacement therapy on the brain. But that’s a topic for another time!

Additional Resource: UC Lecture

References

Filo, S., Shtangel, O., Salamon, N., Kol, A., Weisinger, B., Shifman, S., & Mezer, A. (2019). Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-11319-1

Fjell, A., Walhovd, K., Fennema-Notestine, C., McEvoy, L., Hagler, D., & Holland, D. et al. (2009). One-Year Brain Atrophy Evident in Healthy Aging. Journal Of Neuroscience, 29(48), 15223-15231. https://doi.org/10.1523/jneurosci.3252-09.2009

Peters, R. (2006). Ageing and the brain. Postgraduate Medical Journal, 82(964), 84-88. https://doi.org/10.1136/pgmj.2005.036665

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