Viewpoint - The link between depression and dementia

Professor Clive Ballard and Anne Corbett explore the relationship between these two common conditions.

Patients with Alzheimer's disease may experience depression (Photograph: SPL)

The relationship between depression and dementia is complex. Depression can be a differential diagnosis to dementia and both conditions can be caused by the same underlying pathology, but depression is also a common and important concurrent psychiatric disorder in people with dementia.

Depression as a differential diagnosis
Depression impacts upon cognitive performance and function, largely due to impaired attention and concentration in combination with loss of energy.

In older patients, these three factors in combination frequently lead to scores on standardised cognitive screens, such as the mini-mental state examination, that are below the usual threshold. This triggers a more extensive diagnostic evaluation to assess for dementia.

In a patient with depression as the primary diagnosis, the individual will typically answer 'I don't know' to a lot of questions and will often exhibit a pattern of impairment indicating deficits in attention rather than in memory.

Less frequently, depression can present like typical dementia, usually referred to as depressive pseudo dementia. In both situations depression may be indicated by low mood, a previous history of depression or an unexpectedly rapid pattern of decline.

If there is any question of an underlying depression it is better to treat this rigorously as it is far worse to miss depression than to give a trial of antidepressants unnecessarily.

As dementia and depression commonly co-exist, it is also important to re-evaluate cognitive function once the depression has been successfully treated.

Shared underlying pathology
Cerebrovascular disease, especially sub cortical microvascular pathology, is associated with both an increased frequency of depression and cognitive impairment in older patients. The cognitive impairment is typically slowly progressive with particular impairments in attention, concentration and executive function.

This overlap can create considerable diagnostic problems given these common symptoms but the possibility of sub cortical microvascular disease is worth considering, particularly in patients with longstanding hypertension or other vascular risk factors.

Depression in patients with dementia
Depression occurs in at least 20 per cent of patients with Alzheimer's disease1 and an even higher proportion of patients with vascular dementia or dementia with Lewy bodies.

Longitudinally, two-thirds of symptoms of depression in patients with Alzheimer's disease resolve without treatment over three months.

However, depression is more persistent in the context of vascular dementia.

Among patients with dementia, depression results in considerable additional distress, reduces quality of life, exacerbates cognitive and functional impairment, increases mortality2 and is associated with added carer stress and depression.3

However, the evidence for the benefit of antidepressants in treating these symptoms is limited.4

Tricyclic antidepressants should be avoided in patients with dementia because of the poorly tolerated side-effects, most importantly related to the anticholinergic properties of these drugs. The most investigated alternatives are selective serotonin-reuptake inhibitors (SSRIs), which are better tolerated, but significantly increase the risk of falls.

Although RCTs of sertraline initially indicated promising results, a recent much larger study was very disappointing, and the majority of clinical trials have failed to show benefit over placebo.4,5

Clinically, alternatives such as serotonin-noradrenaline reuptake inhibitors have become more popular but no clinical trials have yet been completed. The ongoing health technology assessment trial study of antidepressants for depression in dementia in the UK will hopefully shed some light on this issue.

Clinical recommendations
Despite the absence of clear-cut evidence, an SSRI is probably still the best treatment option in a patient with Alzheimer's disease or another dementia with severe depression, where the patient is experiencing suicidal thoughts or where there is a serious impact on food and fluid intake.

The optimal duration of therapy is unclear in the absence of any specific studies to inform practice but treatment should probably be continued for at least six months after the resolution of symptoms and for a longer period if the depression has been recurrent.

The situation is even less clear for patients with vascular dementia where the symptoms are more frequent and persistent. There are no specific trials, although studies in stroke patients have suggested that SSRIs are an effective treatment for depression.

In practice, SSRIs are again probably the treatment of choice but the threshold for preferring a pharmacological approach is lower in vascular dementia.

For less severe depression, which is often self-limiting over a few months, non-pharmacological approaches may be preferable. There is good evidence from RCTs that very simple approaches, such as gentle exercise, do confer a significant benefit.

Key points
  • Dementia and depression are independent psychiatric conditions with similar pathologies and symptoms that can occur concurrently.
  • If in doubt, it is better to treat with antidepressants than for depression to remain undiagnosed.
  • In patients presenting with vascular risk factors, sub cortical microvascular disease should be investigated.
  • Depression impacts severely on the quality of life, symptoms and prognosis of people with dementia.
  • Current evidence regarding benefits of antidepressants in patients with dementia is limited, but SSRIs are probably the treatment of choice for severe depression in these patients. Tricyclic antidepressants should be avoided.
  • In less severe cases, non-pharmacological approaches can be effective.
  • Professor Ballard is professor of age-related diseases at King's College London and Ms Corbett is research communications manager at Alzheimer's Society

1. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer's disease. III: Disorders of mood. Br J Psychiatry 1990; 157: 81-6, 92-4.

2. Burns A, Lewis G, Jacoby R et al. Factors affecting survival in Alzheimer's disease. Psychol Med 1991; 21: 363-70.

3. Ballard CG, Eastwood C, Gahir M et al. A follow up study of depression in the carers of dementia sufferers. BMJ 1996; 312: 947.

4. Bains J, Birks JS, Dening TD. Antidepressants for treating depression in dementia. Cochrane Dementia and Cognitive Improvement Group. Cochrane Database Syst Rev 2007; 3.

5. Weintraub D, Rosenberg PB, Drye LT et al. DIADS-2 Research Group. Sertraline for the treatment of depression in Alzheimer disease: week-24 outcomes. Am J Geriatr Psychiatry 2010; 18(4): 332-40.

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