Elsevier

Maturitas

Volume 79, Issue 2, October 2014, Pages 184-190
Maturitas

Review
Depression and dementia: Cause, consequence or coincidence?

https://doi.org/10.1016/j.maturitas.2014.05.009Get rights and content

Abstract

The relationship between depression and dementia is complex and still not well understood. A number of different views exist regarding how the two conditions are linked as well as the underlying neurobiological mechanisms at work.

This narrative review examined longitudinal and cross sectional studies in the existing literature and determined the evidence supporting depression being a risk factor, a prodrome, a consequence, or an independent comorbidity in dementia.

Overall there is convincing evidence to support both the notion that early life depression can act as a risk factor for later life dementia, and that later life depression can be seen as a prodrome to dementia. There is also evidence to support both conditions showing similar neurobiological changes, particularly white matter disease, either indicating shared risk factors or a shared pattern of neuronal damage.

These findings highlight the need to examine if effective treatment of depressive episodes has any effect in reducing the prevalence of dementia, as well as clinicians being vigilant for late life depression indicating the incipient development of dementia, and therefore carefully following up these individuals for future cognitive impairment.

Introduction

Depression and cognitive impairment are both common conditions in old age, and frequently occur together. The inter-relationship between the two clinical entities is complex and still not well understood and further work is needed on examining the temporal relationship and underlying neurobiological networks in order to draw more confident conclusions as to whether the two conditions are linked as risk factors, are part of a continuum, or are two separate conditions. Data from the existing literature devoted to the relationships between dementia and depression can be controversial on account of methodological biases such as differing definitions, variability of assessment tools for both depression and dementia, length of follow up, as well as the primary aim of the study.

Themes emerging from existing studies regarding the relationship have generated a number of different hypotheses. These include (1) depression being an independent risk factor in developing dementia [1]; (2) depression affecting the threshold for manifesting dementia [2]; (3) dementia or cognitive impairment being a feature of depression [3]; (4) the notion of depression being a prodrome of dementia [4]; (5) depression being a reaction to cognitive decline [5] and finally, (6) dementia and depression sharing common risk factors explaining the increased prevalence of both in this population [6], [7], [8], and why they are frequently comorbid.

Regarding attempts to explain the underlying neurobiological mechanisms at work leading to such relationships, again there is no single hypothesis. Ganguli [9] drew reference to the epidemiologic concept of the ‘web of causation’ meaning there is no single cause but rather multiple factors that interact with one another in different ways at different points along the life course. Butters et al. [2] proposed the ‘multiple pathways model’ based on the concept of brain and cognitive reserve. Depression has been found to injure neurons by a number of different mechanisms such as by increased vascular disease [10], inflammation [11], elevated glucocorticoid production [12], as well as amyloid deposition and neurofibrillary formation [13], each of which may lead to hippocampal injury as well as damage in other brain areas. As well as directly leading to dementia, it is proposed that these pathways lower reserve leading to cognitive impairment being expressed earlier and/or more frequently than it would otherwise. The fact that these processes are not mutually exclusive, and more likely synergistic, explains the substantial variability of findings from the literature devoted to this topic.

The objective of this narrative review was to examine recent literature for the purpose of determining what progress has been made about the relationship found between depression and dementia. We approached the review from the hypotheses of depression causing, or acting as a risk factor for dementia, depression occurring as a consequence of dementia (i.e. a symptom of or reaction to dementia, including the concept of depression as a prodromal feature of dementia) and finally, depression occurring as a coincidental finding in dementia.

Section snippets

Method

A search of the electronic databases MEDLINE(R) and EMBASE was conducted using the keywords depression OR depressive* AND (dementia OR Cognitive Dis* OR Vascular OR Multi-Infarct OR Alzheimer*). Limits were set to include all articles from the year 2005 to current and those published in English language. Manual searches of other relevant journals and reference lists of primary articles found from initial searches were also conducted.

Titles and abstracts were reviewed for relevance.

Results

Table 1. provides a summary of all the findings and each section is described in the text below.

Conclusions

Dementia and depression are among the most common disorders of the elderly, having a major impact on quality of life for patients and relatives, increased mortality, and substantial health care and social costs [50], [52]. The relationship between depression and dementia is complex with depression having been reported to be both a risk factor and a prodrome for Alzheimer's disease and other dementia's, and also being a common complication of dementia at all stages. Depression is common in

Contributors

SB did the literature search and wrote the draft. AT supervised and finalised the manuscript.

Competing interests

The authors declare no competing interests.

Funding

The research was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Provenance and peer review

Commissioned and externally peer reviewed.

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