Vol 8, No 2 - Depression in Medicine
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pidemiological studies have implicated chronic depression  as  an  important  predisposing  factor  for dementia in later life. Depression has been shown to be a common antecedent of Alzheimer’s disease, and may be an early manifestation of dementia before the cogni- tive symptoms become apparent.1,2 In particular, patients with depression who later develop dementia usually have a poorer baseline performance in cognitive tasks.3 Several studies have shown that depression is a risk fac- tor for dementia, particularly Alzheimer’s disease, and this  may  be  particularly  important  if  the  depressive episode occurs within 2 years of the diagnosis of demen- tia.3 Indeed, it has been estimated that patients with mild cognitive impairment and depression have more than twice the risk of developing dementia than those of the same age but who do not have depression. This suggests that depression may be a prodrome of dementia.4 Both  depression  and  dementia  are  associated  with inflammatory changes in the brain. The chronic inflam- matory diseases, such as rheumatoid arthritis, are fre- quently associated with depression,5 while proinflamma- tory  cytokines, such  as  interferon  a (IFNa), used therapeutically in the treatment of hepatitis, for example, are known to precipitate depressive episodes in psychi- atrically nondepressed patients.6 An experimental study has also been reported in which rats treated with IFNa showed anxiety behavior in open field, and changes in cytokines in both peripheral blood and in certain brain regions.7 Numerous clinical studies, supported by clinical evidence, have shown that proinflammatory cytokines are raised in the blood of depressed patients.8 Such obser- vations form the basis for the macrophage theory of depression.9 The  possible  link  between  depression, dementia, and inflammatory changes in the brain is also supported by clinical and experimental studies of acquired immune defi- 1 6 3 B a s i c  r e s e a r c h E Copyright © 2006 LLS SAS.  All rights reserved www.dialogues-cns.org Changes in the immune system in depression and dementia: causal or coincidental effects? Brian E Leonard, PhD, DSc; Ayemu Myint, MBBS, MMedSci Keywords: hypercortisolemia; inflammation; proinflammatory cytokine; prosta- glandin E2; kynurenic acid, quinolinic acid; neurodegeneration Author affiliations: Department of Pharmacology, National University of Ireland, Galway, Ireland  (Brian E. Leonard);  Brain and Behaviour Research Institute, Department of Psychiatry and Neuropsychology, University of Maastricht, the Netherlands (Ayemu Myint) Address for correspondence: Brian E. Leonard, Department of Pharmacology, National University of Ireland, Galway, Galway, Ireland (e-mail: belucg@iol. ie) Epidemiological studies show that there is a correlation between chronic depression and the likelihood of demen- tia  in  later  life.  There  is  evidence  that  inflammatory changes in the brain are pathological features of both depression and dementia. This suggests that an increase in  inflammation-induced  apoptosis,  together  with  a reduction in the synthesis of neurotrophic factors caused by a rise in brain glucocorticoids, may play a role in the pathology of these disorders. A reduction in the neuro- protective components of the kynurenine pathway, such as kynurenic acid, and an increase in the neurodegenera- tive components, 3-hydroxykynurenine and quinolinic acid, contribute to the pathological changes. Such changes are postulated to cause neuronal damage, and thereby predispose chronically depressed patients to dementia.    © 2006, LLS SAS Dialogues Clin Neurosci. 2006;8:163-174.