This page contains a Flash digital edition of a book.
Affective disorders, mild cognitive impairment, and risk for dementia

Finally, Wilson et al.21 tested the hypothesis that depressive symptoms increased during preclinical AD. Catholic nuns, priests, and monks without dementia at study onset com- pleted annual clinical evaluations including the administration of the CES-D and clinical classification of MCI and AD. At baseline, participants reported a mean of 1.091.5 depressive symptoms. Those who developed AD (n190) showed no increase in depressive symptoms before the diagnosis was made, a finding not modified by age, sex, education, memory complaints, vascular burden, or personality. No systematic change was observed in depressive symptoms after the AD diagnosis. Among individuals without cognitive impairment at baseline, depressive symptoms did not increase in those who subsequently developed MCI. The authors concluded that there was no evidence of an increase in depressive symptoms during preclinical AD. However, the sample was very mildly depressed at baseline per the CES-D scores, and the partici- pants were all highly educated (mean, 17.893.3 years of education in participants with incident AD vs 18.293.4 years of education in unaffected participants). Perhaps the partici- pants’ education level played a protective role against the development of depression, as recent data showed that higher educational levels seem to have a protective effect against anxiety and depression that accumulates throughout life, whereas low educational levels were significantly associated with anxiety and depression.38 In addition, the participants being catholic nuns, priests, and monks, there was possibly a selection bias.

Anxiety and risk/or dementia. Table 2 presents the design, follow-up duration, sample type, n and diagnosis at baseline, age at baseline, measures of anxiety, and measures of cognition of the studies described in this section.

Per the inclusion criteria of this review, all the studies of

this section had a longitudinal component. The duration of the follow-up ranged from 3 to 17 years, with 2/3 studies having a follow-upB4 years. Only one study had a sample including more than 200 participants.39 The participants in all the studies were elderly, although the age at baseline varied from study to study. The cognitive evaluation manda- tory to assess any cognitive deficit and decline was exhaustive in two of three studies.40,41

Regarding the measures of anxiety, two of three studies39,41

used the Spielberger State-Trait Anxiety Inventory (STAI42) that has good psychometric properties.43 Two-third of the studies39,40 reported an association between the presence of anxiety symptoms and the development of dementia, whereas only one41 reported no association. However, in two studies,39,41 MCI was broadly defined; in fact, the authors included patients meeting the criteria of cognitive- impairment-no-dementia (CIND44) which are less restrictive than the MCI criteria as per Petersen. This methodological choice possibly introduced heterogeneity in both the severity and characterization of cognitive deficits in the MCI patients, which could impact on the presentation of affective symptoms. 27 Palmer and colleagues40 examined the occurrence of NPS

and the relationship to future development of AD in individuals with and without MCI. Three types of NPS were evaluated at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptoms. The NPS occurred more frequently in individuals with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in NCI older adults (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of the individuals presenting with MCI and anxiety symptoms, 83.3% developed AD over follow-up, compared with 6.1% of NCI individuals and 40.9% who had MCI without anxiety. Among individuals with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom. Conversely, among NCI individuals, only depressive mood symptoms were related to AD development. The predictive validity of MCI for identify- ing future AD cases improved in the presence of anxiety symptoms. However, depressive symptoms did not show a statistically significant prediction for AD among patients with MCI because they were highly prevalent in patients with MCI who remained dementia free (31.3%) and patients with MCI who developed AD (37.5%). The authors speculated that in the first group of patients, MCI was related to an underlying psychiatric disorder, and in the second group, MCI and depression were associated with neurodegeneration.

The study of Gallacher et al.39 examined the association of anxiety with incident dementia and CIND in men who only received anxiety assessment at baseline. Medical notes and death certificates of those not seen were also examined. Of 1160 men who were cognitively screened 17 years later, 174 received a diagnosis of CIND, 69 a diagnosis of dementia, 916 remained cognitively intact, and 1 case was undiagnosed. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function, associations with higher anxiety (31st95th centile) were for CIND (OR 2.31, 95% CI 1.204.44) and for dementia (OR 2.37, 95% CI 0.985.71). These associations were slightly stronger for nonvascular (OR 2.45, 95% CI 1.284.68) than for vascular impairment (OR 1.94, 95% CI 0.774.89). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examina- tion of the Elderly subscales, found some evidence for decline in learning memory with higher anxiety score, but not for any other subscale. Anxiety was thus a risk factor for CIND and dementia. This study has a major problem: there was no cognitive assessment at baseline. Therefore, the possibility that some participants might have had MCI at onset of the study cannot be excluded.

The third study41 assessed the impact of state and trait anxiety in predicting conversion to AD in MCI and controls. Baseline.predictors for follow-up conversion to AD included the STAI. At baseline, MCI patients had higher levels of state and trait anxiety than controls, with no difference between future AD converters (n39) and non-converters. In age- stratified Cox proportional hazards model analyses, STAI State was not a significant predictor of conversion to AD (STAI State530 vs30 risk ratio, 1.68; 95% CI, 0.75, 3.77;

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

Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89