Dotson, V. M. et al. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology 75, 27-34

National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, USA.
Neurology (Impact Factor: 8.29). 07/2010; 75(1):27-34. DOI: 10.1212/WNL.0b013e3181e62124
Source: PubMed


A history of depression has been linked to an increased dementia risk. This risk may be particularly high in recurrent depression due to repeated brain insult. We investigated whether there is a dose-dependent relationship between the number of episodes of elevated depressive symptoms (EDS) and the risk for mild cognitive impairment (MCI) and dementia.
A total of 1,239 older adults from the Baltimore Longitudinal Study of Aging were followed for a median of 24.7 years. Diagnoses of MCI and dementia were made based on prospective data. Participants completed the Center for Epidemiologic Studies Depression Scale at 1- to 2-year intervals and were considered to have an EDS if their score was > or = 16. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazards models were conducted to examine the risk of MCI and dementia by number of EDS.
We observed a monotonic increase in risk for all-cause dementia and Alzheimer disease as a function of the number of EDS. Each episode was associated with a 14% increase in risk for all-cause dementia. Having 1 EDS conferred an 87%-92% increase in dementia risk, while having 2 or more episodes nearly doubled the risk. Recurrence of EDS did not increase the risk of incident MCI.
Our findings support the hypothesis that depression is a risk factor for dementia and suggest that recurrent depression is particularly pernicious. Preventing the recurrence of depression in older adults may prevent or delay the onset of dementia.

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    • "The number of previous episodes of depression positively correlates with serum IL-1β, TNF-α and neopterin levels, suggesting a role for CMI interactions with O&NS in the aetiology and course of recurrent depression and neuroprogression. This is important given the data showing that recurrent depression increases the risk of Alzheimer's disease [68]. However, it should be noted that changes in plasma IL-2 and IFN-ү levels are not always evident in depression [69], perhaps indicative of the heterogeneous nature of the disorder or of different stages of chronicity and neuroprogression. "

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    • "A number of factors have been shown to increase gut permeability, including dietary fats [7], stress [6] and alcohol [8], including binge alcohol drinking [9], whilst a number of factors can decrease permeability or help to maintain gut tight junction integration, including dietary whole grains [10] and melatonin [4], with the latter preventing the effects of alcohol on gut permeability [8]. Recent work on the role of gut permeability in other medical conditions has focussed on its impact in the aetiology and course of depression, in turn driving the association of recurrent depression with other medical conditions, including Alzheimer's disease [11]. As such, we will first look at the role of gut permeability in depression, linking this to the aetiology of depression-associated conditions. "
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    ABSTRACT: Recent work has highlighted the importance of immune inflammatory processes, oxidative and nitrosative stress (O&NS) and tryptophan catabolites (TRYCATs) in the aetiology of depression and many depression-associated disorders, including other psychiatric, neurodegenerative and wider medical disorders. A recently researched aspect of the aetiology and course of depression has focussed on the role of gut permeability and gut microbiota. Increased gut permeability is evident in many medical conditions, contributing to increased immune inflammatory cytokines, O&NS and neuroregulatory TRYCATs. By driving tryptophan down the kynurenine pathways and away from serotonin, Nacetylserotonin and melatonin synthesis, such processes alter the nature of central processes, but also contribute to changes in gut permeability regulation. Here we look at the role of decreased melatonin in gut permeability, especially via its regulation of the inflammasome. This has important consequences across a host of medical conditions, including Alzheimer’s disease, non-alcoholic fatty liver disease, obesity, fibromyalgia and alcoholism, as well as in the aetiology and course of depression. Such work emphasises the importance of central and systemic interactions, and has implications for the etiological conceptualisation, classification, course and treatment of a diverse array of medical conditions.
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    • "In order to specify this correlation, the Baltimore Longitudinal Study of Aging followed 1,239 old adults for a median period of 25 years, and showed that having one severe MDE leads to an 87% increased risk of dementia (hazard ratio; 1.87). On the same basis, having two or more episodes nearly doubled the risk (hazard ratio; 2.08), and each episode was associated with a 14% increased risk of dementia (Dotson et al., 2010). One of the suggested mechanisms that may bind depression and dementia is the reduced size of the hippocampus, which is known as one of the components of Alzheimer's dementia diagnosis. "

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