Aging originates from a diverse group of mechanism that makes a gray zone between normal aging and pathological aging process.[25
] Normal aging is associated with some degree of neuron loss and volume loss with increasing adjacent glial cells.[26
] Recent studies have shown that loss of brain volume is due to loss of neuronal cell size rather than loss of cell volume,[27
] and the cognitive decline associated with normal aging is because of dysfunction rather than loss of neurons or synapses. Decrease in the amount of synaptic proteins involved in structural plasticity of axons and dendrites have suggested that disturbed mechanism of plasticity may contribute to cognitive dysfunction during aging.[28
] Noninvasive technique like volumetric MRI has shown a progressive decline in cerebral hemisphere by 2-3% a decade and increase in ventricular volumes by 2% a decade.[29
] There was also a whole brain volume (WBV) decline by 0.22 a year between the ages of 20-80 years with hastened decline with advancing age.[29
] Healthy volunteers, an age-related decline in the volume of the prefrontal cortex, insula, anterior cingulategyrus, superior temporal gyrus, inferior parietal lobule, and precuneus was found. These decreases might contribute to the cognitive changes during normal aging. In patients with AD, a significant reduction of gray matter volume in the hippocampalformation and EC bilaterally was noted. The changes in regional volume are not uniform. Some regions, such as the PFC, show particularly dramatic changes in volume, while other regions, such as the occipital cortex, are relatively unaffected by normal aging.[3
] The largest age-related volumetric changes in older adulthood appear to occur in the PFC,[35
] approximately average volume loss of approximately 5% per decade starts from 3rd
decade of life.[36
] The biggest age-related volume loss occurs in the lateral PFC, with an estimated rate of loss of 0.91% per year.[37
] Orbito-frontal PFC declination were nearly as large as lateral PFC, with an estimated annual loss of 0.85%.[37
] But in case of Alzheimer's disease greatest degeneration is seen in the inferior PFC.[38
] Also gradual volume loss is observed in the striatum. It is heavily enriched with dopaminergic neuron, which connects it to the PFC. Striatal volume declines at about 3% per decade,[39
] while caudate volume declines at approximately 0.75% per year.[37
Medial temporal lobe consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events. These volumes also decline during normal aging. Adult lifespan studies (with participants in their 20s to 80s) with intervals of 5 years have estimated the rate of decline in hippocampal volume at 0.79-0.86% per year.[3
] The declination in EC volume however, was smaller- with the estimated rate of change being approximately 0.33%, although this accelerates somewhat in later life.[40
Longitudinal measurements of hippocampal atrophy increase many-fold from a range of 0.2-3.8% per year in normal elderly to a range of 4.9-8.2% per year in AD.[41
] Decline in EC volume in MCI patients is twice, compared to age-matched controls.[42
] In general, these results suggest that normal aging has modest structural effects on the hippocampus and adjacent medial temporal lobe structures. Pathological processes related to MCI and AD, however, have severe effects within the EC even early in disease progress, which reduces the potential for effective hippocampal involvement in memory function.
Brain areas which are involved with cognitive processes affected in AD showed robust relationship with white matter degeneration and gray matter (GM) degeneration. Therefore, cortical function and white matter (WM) degeneration are related in aging and dementia. A study done by Yulin[43
] measured both absolute and fractional %GM and %WM volumes in healthy adults aged of 20–86 years and evaluated the data by age and sex. This study showed that the rate of change in %GM and %WM with aging does not depend on sex, although female subjectshave slightly higher %WMs, compared to male subjects.
This study also found a 4.9% difference in %GM between the younger groupand the older groups. The decline of volume of %GM occurs by a relatively young age (age 20 years), and the decline occurs constantly in a linear fashion.While the %WM, in contrast, shows a quadratic pattern of change, volume increases until an age of around 40 years. But once WM degeneration starts at age of 40, the loss is more consistent and faster than GM.
Modern noninvasive imaging techniques are an excellent means to examine age-related changes from pathological changes. CT scan and MRI help us gain detailed assessment of brain structures. The functional state of brain can be best detected by PET scan; Flurrine-18-fluorodeoxyglucose has been used before to reveal alteration of regional metabolic rate of normal aging and other psychiatric disorders.[44
] Various regional metabolic activities varied among subjects within same age group as well as over decades. The anterior posterior gradient changes over the time and with advancing age, because of significant decrease in frontal lobe activity in later years. Less frontal lobe activity becomes more notable after age of 30 years, but more dramatic decline of frontal brain metabolic activity occurs after age of 60, and this is the time when temporal lobe metabolic activity also starts to decline.[45
] Cerebellum to cerebral cortex metabolic activity ratio tends to increase with age, and it is consistent with decrease metabolic activity of cerebral cortex, which becomes more prominent after age of 40 years. At the same time cerebellum's metabolic activity remains constant up to age of 40 years.[46
] Findings from other research[47
] showed that metabolic activity of frontal, temporal and parietal brain decreases with aging but this decline is more rapid in case of frontal lobes.[48
] One study was done[49
] to detect cerebral metabolites like N-acetyl aspartate (NAA), and choline (Cho) and creatine (Cr) in vivo
by newer proton magnetic resonance spectroscopy. NAA is a specific neuron marker, as it is found at high concentration almost only in neurons.[50
] The major findings of this study were: A) Hippocampal NAA/Cho and NAA/Cr decreases with advancing age, whereas Cho/Cr remains relatively stable. This implies that NAA ratio declines are mainly due to decreases of NAA. B) Hippocampal volume decreases with age, C) Hippocampal NAA ratios and volume change occurs at similar relative rates with advancing age. This is consistent with the view that hippocampal volume loss is due to neuronal loss. Metabolites ratio and volume of hippocampus decrease starts consistently from age of 36 years, and it occurs in a linear fashion with aging.