Research reportDepressive symptoms and cognitive decline: A longitudinal analysis of potentially modifiable risk factors in community dwelling older adults
Introduction
Depression and cognitive decline in later life are, in many ways, linked disorders. Older adults with depression are at particularly high risk of cognitive decline and it has been documented that approximately 60% of non-demented older adults with depression attending secondary care already have significant cognitive impairment (Bhalla et al., 2006, Butters et al., 2004). A recent meta-analysis of prospective population studies found that older adults with depression have an almost two-fold risk of all cause dementia with significantly increased risk for both Alzheimer's and vascular dementia (Diniz et al., 2013). Depression in later life sometimes occurs as a prodromal symptom of neurodegenerative disease but it also behaves as a true risk factor, and a remote history of depression, up to 25 years in advance of cognitive decline, has previously been associated with increased incidence of dementia (Green et al., 2003, Ownby et al., 2006). The number of prior depressive episodes has been linked to dementia risk in a dose-related fashion (Kessing and Andersen, 2004), and when depression occurs in the context of mild cognitive impairment it is associated with accelerated progression to dementia (Lu et al., 2009). A recent review and meta-analysis which examined several potentially modifiable risk factors for dementia, reported a population attributable risk fraction of depression for dementia of around 10%, and estimated that a reduction of 10% in depression prevalence would be associated with 326 000 less cases of dementia worldwide (Barnes and Yaffe, 2011).
Despite the knowledge that depression is a risk factor for cognitive decline in later life there are no interventions proven to reduce cognitive decline in older adults with depression. This in part, reflects the lack of clarity regarding how the relationship between depression and cognitive decline is mediated. There are several plausible mechanisms for this association including adverse health behaviours such as physical inactivity and physiological changes such as inflammatory activation associated with the depressive state (Moylan et al., 2012). Physical inactivity has been robustly associated with increased risk of cognitive decline in several observational studies and interventions to increase physical activity in older adults with memory complaints without depression have resulted in a modest improvement in cognitive function (Lautenschlager et al., 2008, Yaffe et al., 2001). Inflammatory activation is frequently a feature of depression and has been associated with increased risk of cognitive decline (Dowlati et al., 2010, Gorelick, 2010). Metabolic syndrome and other vascular risk factors such as diabetes, hypertension and smoking have been associated with both cognitive decline and depression (Richard et al., 2012, Yaffe et al., 2004).
To the best of our knowledge, no study to date, has examined these risk factors in the context of depressive symptoms to determine if they mediate the association between depressive symptoms and cognitive decline. If these potentially modifiable risk factors do mediate the relationship then they could be important therapeutic targets in interventions that seek to reduce cognitive decline in older adults with depression. The objectives of the study were to determine if depressive symptoms are associated with cognitive decline in older adults and explore how this effect is mediated.
Section snippets
Sample
The English Longitudinal Study of Ageing (ELSA) is an ongoing cohort study based on a nationally representative sample of the community dwelling population aged 50 years and over in England (Cheshire et al., 2012). The present study reports on those who participated in a clinical assessment at wave 2 and a smaller follow up sample who participated in the clinical assessment at wave 4. Participants gave informed consent to participate in the study and ethical approval was obtained from the
Results
Seven thousand six hundred and ten study participants were included in the baseline analysis of whom 4196 (55.1%) were female (Table 1). One thousand one hundred and thirty three (14.9%) reported clinically significant depressive symptoms at baseline. Depressed older adults had a greater number of chronic medical conditions and had more functional and cognitive impairment at baseline. Older adults with depression were also significantly more likely to have low physical activity, greater
Summary of main findings
In this longitudinal analysis of community dwelling older adults we found that depressive symptoms displayed an independent and dose-related association with cognitive decline. This finding is consistent with findings from other population studies in older adults that have reported an independent and dose-related relationship between depressive symptoms, cognitive decline and dementia (Dotson et al., 2010, Saczynski et al., 2010). In addition we found that older adults with depression were more
Conclusion
In conclusion, we found that depressive symptoms displayed an independent relationship with cognitive decline. This effect was mediated by physical inactivity and inflammation although vascular risk factors such as hypertension, diabetes and smoking also contributed. The findings support the proposition that these risk factors should be screened for and treated in older adults with depression as part of a comprehensive intervention, which includes physical exercise, to both relieve depressive
References (48)
- et al.
Executive dysfunction and the course of geriatric depression
Biol. Psychiatry
(2005) - et al.
The projected effect of risk factor reduction on Alzheimer's disease prevalence
Lancet Neurol.
(2011) - et al.
Persistence of neuropsychologic deficits in the remitted state of late-life depression
Am. J. Geriatr. Psychiatry
(2006) - et al.
A meta-analysis of cytokines in major depression
Biol. Psychiatry
(2010) Involvement of brain-derived neurotrophic factor in late-life depression
Am. J. Geriatr. Psychiatry
(2013)- et al.
What predicts persistent depression in older adults across Europe? Utility of clinical and neuropsychological predictors from the SHARE study
J. Affect. Disord.
(2013) - et al.
A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2011) - et al.
A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial
Lancet
(2015) - et al.
Systemic inflammation induces apoptosis with variable vulnerability of different brain regions
J. Chem. Neuroanat.
(2005) - et al.
Connections between sleep and cognition in older adults
Lancet Neurol.
(2014)