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Mind & Brain, the Journal of Psychiatry

the use of several self-reported measures (thus open to bias) and the utilization of only the CDR16 to assess cognition which is insufficient to properly characterize cognitive deficits and functions. The CDR is principally based on observation and on a clinical interview with the patient and the informant16.

The following three studies report a greater association between apathy and subsequent development of dementia than between depressive symptoms and cognitive decline. The aim of Vicini Chilovi et al. study18 was to evaluate the role of apathy and depression in the conversion to dementia among MCI patients. At baseline, 40.3% patients were classified as MCI normal, 30.7% as MCI depressed, 16.9% as MCI depressed-apathetic and 12.1% as MCI-apathetic. The rates of conversion were 24% for MCI normal, 7.9% for MCI depressed, 19% for MCI depressed-apathetic and 60% for MCI-apathetic. Apathy was a risk factor for conversion apart from age, functional and cognitive status at baseline (OR 7.07; 95% CI 1.925.1; p0.003). In contrast, MCI depressed subjects had a reduced risk of conversion (OR0.10; 95% CI 0.020.4; p0.001). Unfortunately, this study did not include a comparison (healthy) group, which limits the conclusions that can be drawn. Nevertheless, these findings argue for a differential role of apathy and depression in the development of dementia.

Another study28 evaluated whether depression or apathy in

newly-diagnosed A-MCI increases the risk of progressing to AD. Cox proportional hazard models with 95% confidence intervals were used to test the hypothesis that apathy or depression increases the risk of developing AD. At baseline, 36.6% A-MCI patients had a diagnosis of depression and 10.7% had apathy. Patients with both A-MCI and apathy had an almost sevenfold risk of AD progression compared to A- MCI patients without apathy (HR6.9; 2.320.6), after adjustment for age, gender, education, baseline global cognitive and functional status, and depression. Furthermore, the risk of developing AD increased 30% per point on the Neuropsychiatric Inventory (NPI30) apathy item (HR1.3; 1.11.4). There was no increased risk of developing AD in A-MCI patients with either a diagnosis or symptoms of depression. In conclusion, apathy, but not depression, predicted the conversion from A-MCI to AD. Although apathy is a complex’construct,31,32 the evaluation of apathy in the last two studies18,28 was performed only using a structured interview and the input of the caregiver oh the NPI which includes.only one item on apathy. However, the Apathy Inventory33 which was especially designed to evaluate the apathy syndrome is a reliable and valid measure for the characterization and quantification of apathy.34,35

Interestingly, the next study19 addressed the shortcomings

of the previous research regarding the evaluation of apathy. The authors examined the influence of apathy dimensions, such as emotional blunting, lack of initiative, and lack of interest, on the risk of developing AD in patients with A-MCI and depressive symptoms. Apathy was measured using the Apathy Inventory,36 the French validated version of the Apathy scale.33 At follow-up, 27.6% patients had developed AD. The

M&B 2011; 2:(1). July 2011 26

risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses and controlling for age, gender, and education, the difference between survival curves was significant for lack of interest. The authors therefore concluded that lack of interest, a mild behavioral sign, could be an indicator of decline in MCI patients. However, there was no control (healthy) group which limits the conclusion about the lack of interest as a predictor of cognitive decline.

Three studies did not find a relationship between depressive symptoms and progression to dementia. Ramakers and colleagues23 investigated the predictive accuracy of depres- sion, anxiety, apathy and sleeping problems for AD, and whether the predictive accuracy was modified by age, the presence of A-MCI or the length of follow-up. Affective symptoms were present in 5070% of the patients. Over the follow-up periods, 79 patients developed AD and 11 patients developed other types of dementia. Depression was asso- ciated with a lower risk for AD only in patients without A-MCI (OR 0.34, 95% CI 0.130.93, p0.036), but not in patients with A-MCI (OR 1.1, 95% CI 0.502.3, p0.85). Moreover, anxiety was related to the risk for AD differently between patients diagnosed with AD at 5-year follow-up (OR 0.23, 95% CI 0.080.66, p0. 007) and patients diagnosed with AD at 10-year follow-up (OR 1.7, 95% CI 0.329.01, p 0.539). Affective symptoms were thus associated with a decreased risk for AD but only in non-amnestic MCI. The authors concluded that the risk may thus be dependent on the MCI subtype or length of follow-up, but it does not depend on age. This study presented some limitations, especially regarding sample size which potentially had an impact on statistical power. There were only 63 participants at 10-year follow-up, and only 42% of the participants presented with A-MCI at follow-up. In addition, there was no pathological confirmation of the diagnoses.

In the study of Becker et al.,20 all participants had at least

three visits with measures of cognition (Modified MMSE; 3MSE37 and mood state CES-D22) before the beginning of the study. Participants were classified according to (1) whether they showed a high negative correlation between their CES-D and 3MSE scores (ie, indicating that greater depression was linked to poorer cognition) and (2) whether they showed persistently elevated CES-D scores. The study outcome, development of dementia (n48), was based on consensus classifications, which were based on detailed neuropsycho- logical (Table 1) and neurological exams. The authors did not find consistent relationship between mood states, either alone or in relation to cognitive status, and the subsequent development of dementia. The individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistendy depressed mood were also no more likely to develop dementia than those without persis- tently depressed mood. This study had however some limitations. The assessment of mood disorders (depression) was made using only a short form of the CES-D. In addition, a survivor bias may have affected the findings.

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