Regular Research ArticleRole of Depression in Predicting Time to Conversion to Mild Cognitive Impairment
Introduction
Mild cognitive impairment (MCI) is a relatively common condition characterized by mild cognitive symptoms in the absence of functional impairment.1 It has a heterogeneous range of outcomes, including dementia, and is therefore sometimes considered a “prodromal” phase before dementia. In amnestic MCI (aMCI), the predominant deficit is of episodic memory.2
Neuropsychiatric symptoms are common in MCI, occurring in 35%–85% of cases.3 It has been suggested that presence of these symptoms may predict conversion from MCI to dementia,4, 5 although research findings in this area are inconsistent. Even less is known about the relationship between neuropsychiatric symptoms and the risk of developing MCI: Several studies,6, 7, 8, 9, 10 including a meta-analysis of four population-based, longitudinal studies comparing the incidence of MCI between subjects with and without depression,11 have shown that cognitively normal subjects with depressive symptoms are at increased risk of developing MCI. For example, in the largest of these studies, over 6,000 cognitively intact women between the ages of 65 and 79 taking part in the Women's Health Initiative Memory Study were assessed for depressive symptoms at baseline and then evaluated annually for the development of cognitive impairment.7 The authors found that the presence of clinically significant symptoms of depression at baseline was associated with a hazard ratio of 1.98 (95% confidence interval: 1.33–2.94) for the development of MCI during the 5.4-year mean follow-up period. However, other studies have shown no such relationship,12, 13 and reviews of this area have been unable to reach firm conclusions due to conflicting results.14 There has been increasing interest, of late, in the relationship between cognitive and psychiatric disorders in older patients; for example, a recent editorial in the American Journal of Geriatric Psychiatry on the subject concluded that this was an important area to attend to with the aim of “increasing our ability to predict cognitive decline among those with late-life psychiatric disorders.”15
The APOE ε4 allele is associated with an increased risk of development of dementia.16 The effect of APOE genotype on the risk of developing MCI is less clear, although most studies suggest that having at least one APOE ε4 allele does increase risk17, 18, 19, 20 and increase the rate of cognitive decline.21 As noted in the editorial mentioned above, little work has been done on the interaction between genetic risk markers for cognitive impairment and neuropsychiatric dysfunction.15
We set out to establish whether, in a population-based cohort of subjects with normal cognition, the severity of depressive symptoms at baseline was related to the time taken for MCI to develop and whether it interacted with the known risk factors of increasing age and APOE ε4 carrier status.
Section snippets
Methods
The population and methods used for investigating the incidence of MCI in this study are identical to those reported in a previous study of the role of verbal expression and learning in predicting the time of conversion to MCI.22 Some parts of the methodology are thus reproduced verbatim below.
Results
One hundred twenty-six subjects from the OPTIMA database were eligible for inclusion in the study. During the 20-year follow-up period, 50 subjects (39.7%) converted to MCI and their conversion durations were thus interval-censored, whereas the remaining 76 (60.3%) were still cognitively healthy at their last recorded episode. Their conversion durations were thus considered as right-censored. The baseline characteristics of the study subjects are summarized in Table 1.
Using the AFT model, a
Discussion
The results of this study show that a greater severity of depressive symptoms (as measured by GDS) at baseline in cognitively normal APOE ε4 noncarriers accelerates the time to conversion to MCI. No significant relationship between GDS at baseline and time to conversion to MCI was identified in APOE ε4 carriers. No other relationship between subject demographics (such as education and gender) and time to conversion to MCI was identified aside from the known risk factors of age, APOE ε4 carrier
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Katherine Dean and Abderrahim Oulhaj are joint first authors.