Redundancy is evident when individuals incur substantial neuronal loss before the appearance of clinical symptoms. Thus, brain reserve capacity posits that individual differences in neural redundancy translate into differences in thresholds for vulnerability to or protection from clinical symptoms after brain damage. The concept of cognitive reserve developed by Stern (eg, refs 121 ,122) is similar but rather than being based on differences in brain size Inhibitors,research,lifescience,medical or neuronal count, emphasizes
differences in the efficiency or manner in which tasks are performed or information is processed. Both brain reserve and cognitive reserve explain the role of risk and protective factors for cognitive impairment (including progressive decline into dementia), associated with brain damage. For example, higher educational attainment, larger head size, larger brain volume,123 social engagement, 124 physical activity,125 and leisure cognitive activity126,127 may result in greater
redundancy and/or efficiency and therefore reserve, thereby offering protection against Inhibitors,research,lifescience,medical exhibiting clinical Inhibitors,research,lifescience,medical symptoms of dementia. Similarly, lower levels of these protective factors may reduce neuronal or functional redundancy leading to earlier dementia symptom onset for a given level of CNS damage. While certain mechanisms may alter an individual’s risk to develop (or change the rate of development of) ADrelated pathology (eg, P-amyloid deposition), other mechanisms alter the Inhibitors,research,lifescience,medical strength of association this website between these biological changes and the time to develop clinical disease. We propose that depression alters an individual’s risk of cognitive dysfunction, shortening the latent period between the development, of AD neuropathology and the onset, of clinical dementia, thus increasing the incidence and prevalence of AD among Inhibitors,research,lifescience,medical older adults with depression. Proposed multiple pathways model We propose that
the reserve threshold theory is the key explanatory mechanism behind the late-life depression/dementia association. That is, through a number of processes (several described here), depression injures neurons, thus lowering reserve such that cognitive impairment Unoprostone is expressed earlier and/or more frequently than it would otherwise. As depicted in , depression is linked to vascular disease, especially in the frontostriatal area. Depression also is linked to elevated glucocorticoid production, as well as amyloid deposition and neurofibrillary formation, each of which may lead to hippocampal injury. Bach of these processes adds to the total brain injury burden, lowering reserve and vulnerability to express cognitive impairment. These links and processes are not mutually exclusive; many are likely synergistic, so that, they act to varying degrees across groups of individuals. This accounts for the substantial heterogeneity of the mood disorder and the presence (or absence) of a cognitive disorder and its clinical course.