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Affective disorders, mild cognitive impairment, and risk for dementia RESULTS

Affective Disorders and Risk for Dementia Systematic Reviews

The results of three literature reviews1113 supported the recommendation of the Second Canadian Conference on the Development of Antidementia Therapies. In the first review,11 21 peer-reviewed papers published before December 2006 were analyzed. Each of these studies included at least 20 patients with MCI and behavioral data. Eight were population-based studies, and 12 used convenience samples from tertiary memory disorder clinics and research databases. Behavioral abnormalities were reported in 3575% of patients with MCI; the most common problems were depression; apathy, anxiety, and irritability. The authors explained the variability in symptom prevalence by the different sampling methods, MCI diagnostic criteria, and behavioral instruments used. According to this review, there is a compelling body of evidence indicating that MCI patients with behavioral features, especially depression and agitation, are more prone to developing AD than patients without these features. However, longitudinal data for apathy, anxiety, psychosis, disinhibition, agitation, euphoria, aberrant motor behavior, and irritability were very scarce and sometimes missing.

The second review12 found that generalized anxiety was the

most common anxiety disorder in older individuals, with a lifetime prevalence of 10.2%. Cross-sectional investigations generally supported the hypothesis that the presence or severity of anxiety is associated with lower cognitive perfor- mance in older adults. Only a few longitudinal studies investigated anxiety as a predictor of cognitive decline in older individuals, and the evidence was controversial, possi- bly due to investigational differences of how anxiety was measured. The ability to predict cognitive decline from baseline anxiety thus may have been attenuated by measuring neurotic traits rather than clinically significant anxiety. This aspect will be further developed in Section ‘‘Anxiety and Risk for Dementia’’ of this article.

In another review,13 PubMed (up until August 31, 2008) was systematically searched for articles on NPS in MCI. Only articles using strict selection criteria were included: (1) the study had to use a clear definition of MCI not only based on a Mini-Mental State Examination (MMSE14) score and/or other global cognitive or clinical scales; (2) the NPS had to be collected using standardized instruments; and (3) the pre- valence and/or incidence rates of NPS had to be described in the text. Twenty-seven articles met the selection criteria; of these articles, only ten were common with those included in the first review.11 Of the 27 articles retained by the authors, 52% used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritabil- ity. Hospital-based samples reported a higher global pre- valence of NPS than population-based studies; this

discrepancy probably reflected differences in demographics, study settings, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI, or may predict the conversion of MCI to AD. NPS were thus very prevalent in patients with MCI, displaying a similar pattern of symptoms compared to dementia and AD.

Prospective Longitudinal Studies

Six prospective longitudinal studies and four prospective cohort studies were found to report the results on the presence of depressive symptoms and/or apathy and the development of MCI and dementia. These results are presented in Section ‘‘Depressive and Apathetic Symptoms and Risk for Dementia’’. Only three studies were found on the presence of anxiety symptoms and the risk for dementia. These results are presented in Section ‘‘Anxiety and Risk for Dementia’’.

Depressive and apathetic symptoms and risk for dementia. Table 1 presents the design, follow-up duration, sample type, n, age and diagnosis at baseline, as. well as measures of affective symptoms and of cognition utilized in the studies of this section. The following paragraphs present the results of the studies.

Per the inclusion criteria of the present review, all the

studies of this section had a longitudinal component. The duration of the follow-up ranged from 2 to 13 years, with 60% of the studies having a follow-up54 years. Seventy percents of the studies had a sample including more than 200 participants and 40% had a sample involving more than 500 individuals. The participants in all the studies were elderly, although the age at baseline (when indicated) varied from study to study. The cognitive evaluation mandatory to assess any cognitive deficit and decline was generally exhaustive. The only exception was Cherbuin and colleagues’ study15 which utilized only the Clinical Dementia Rating Scale (CDR16) to document the cognitive deterioration.

Regarding the measures of affective disorders, there was

some discrepancy between the studies. Only 4 out of 10 studies used at least two questionnaires or scales to assess affective disorders.15,1719 However, the majority of the studies utilized only one short instrument to investigate these symptoms. For instance, two studies20,21 used the Center for Epidemiological Studies-Depression Scale (CES-D22)io- item short version, while another study23 used only the Hamilton Depression Rating Scale (HDRS.24 Interestingly, those studies did not find evidence that mood disturbances were linked to the development of dementia.

Nevertheless, 70% of the studies15,1719,25,26,28 reported an

association between the presence of depressive and/or apathetic symptoms and the development of dementia, whereas only 30%20,21,23 reported no association between these affective symptoms and the subsequent development of dementia (see Table 1). However, the question is complicated.


M&B 2011; 2:(1). July 2011

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