Oxidative Stress and Neurodegeneration: An Inevitable Consequence of Aging? Implications for Therapy

Parallels Between Major Depressive Disorder and Alzheimer’s Disease: Role of Oxidative Stress and Genetic Vulnerability

“…One of the reasons to use this approach is that the neurobiological and molecular processing mechanisms may be studied more openly, without the restriction of ambiguous clinical phenotypes, threshold measures, observation, and opinion. Furthermore, we reported in a previous study (Rodrigues et al 2010) that if we consider a closed system cohort - without member inclusion from birth or exclusion at death - going through the continuum of aging, normal aging cognitive decline, MCI and AD; and if all its participants reach 100 years of age, 83% would be affected by AD or SDAT, and the remaining 17% of this 100 year old community would be either normal (not senile dementia--NSD) or affected by other types of neurological disease. Thus, according to the typical AD prevalence, at 100 years old, SDAT participants would be by far the norm (83%), and NSD plus senile dementia of other types would be the exception (17%); factors that make statistical AD evaluation erratic and confusing as to its real prevalence/incidence in the world (Rodrigues et al 2010).…”

“…Furthermore, we reported in a previous study (Rodrigues et al 2010) that if we consider a closed system cohort - without member inclusion from birth or exclusion at death - going through the continuum of aging, normal aging cognitive decline, MCI and AD; and if all its participants reach 100 years of age, 83% would be affected by AD or SDAT, and the remaining 17% of this 100 year old community would be either normal (not senile dementia--NSD) or affected by other types of neurological disease. Thus, according to the typical AD prevalence, at 100 years old, SDAT participants would be by far the norm (83%), and NSD plus senile dementia of other types would be the exception (17%); factors that make statistical AD evaluation erratic and confusing as to its real prevalence/incidence in the world (Rodrigues et al 2010). These impressive statistical results, we believe, may represent a chance to go forward on the aging stress-anxiety-depression and neurodegenerative illnesses continuum looking for ‘a common or analogous or alike molecular, biochemical and biological brain mechanisms on AD and depressive spectra’ (Rodrigues et al 2010).…”

“…Following the same strategy as that used for depression, we shall consider Alzheimer’s disease and other dementias as a psychobiological continuum, beginning with aging phenotypes and adding variant phenotypes, particularly cognitive, as the aging cognitive impairment, mild cognitive impairment (MCI), gradually progressing into mild to moderate forms of senile dementia of the Alzheimer type (SDAT) (Rodrigues et al 2010), and ending with deep to very severe dementia. One of the reasons to use this approach is that the neurobiological and molecular processing mechanisms may be studied more openly, without the restriction of ambiguous clinical phenotypes, threshold measures, observation, and opinion.…”

“…Thus, according to the typical AD prevalence, at 100 years old, SDAT participants would be by far the norm (83%), and NSD plus senile dementia of other types would be the exception (17%); factors that make statistical AD evaluation erratic and confusing as to its real prevalence/incidence in the world (Rodrigues et al 2010). These impressive statistical results, we believe, may represent a chance to go forward on the aging stress-anxiety-depression and neurodegenerative illnesses continuum looking for ‘a common or analogous or alike molecular, biochemical and biological brain mechanisms on AD and depressive spectra’ (Rodrigues et al 2010). …”

“…Oxidative stress is one of the main molecular and cellular factors in triggering “cascades” which may interact with the most varied molecular phenotypes, impairing neuronal function and transforming subclinical, physiological, and homeostatic neural defense mechanisms toward disease and neuronal disintegration (Jellinger 2007). Further, it is possible to consider oxidative stress as a dynamic continuum of brain response in the same context as aging, aging cognitive decline, depression, mild cognitive impairment, and Alzheimer’s disease, once the first two physiologic phenotypes proceed and transform into the last three pathologic phenotypes, depending on internal and external conditions (Rodrigues et al 2010). In this review we will also consider chronic major depressive disorder, in comorbidity with anxiety and/or psychological stress, as a continuous spectrum of subclinical, clinical, and biologic molecular phenotypes (Akiskal and Lewis 2005).…”