Our major findings include the following: 1) SSD is common in MCI and the most frequently endorsed symptoms from the GDS included memory problems, lack of energy, preference for staying at home, and limitations in activities, 2) Total SSD severity and endorsement of specific depressive symptoms did not differ at baseline between MCI groups, 3) The majority of MCI participants demonstrated either stable or fluctuating SSD and stability of SSD total severity scores did not differ between MCI groups, and 4) Stability of 4 specific depressive symptoms from the GDS (memory problems, activity and interest limitations, preference for staying at home, and feelings of helplessness) over 36 months differentiated cognitively stable MCI participants from MCI converters. However, only endorsement of memory problems was associated with conversion to dementia after accounting for other clinical variables. Each of these findings will be discussed below.
With respect to the overall prevalence of SSD at baseline in this sample, 77% exhibited one or more symptoms of depression on the GDS. If item 10 (memory problems) was excluded from analysis, 55% of the sample endorsed SSD on this measure demonstrating that 22% of the sample endorsed isolated memory problems. Our results suggest that in addition to memory problems, lack of energy, preference for staying at home, and dropping of activities and interests were the most commonly endorsed SSD for the sample.
Overall, the prevalence of SSD obtained from the entire GDS in our sample was higher than estimates of SSD in MCI using other measures of depression, which typically report the prevalence of SSD of approximately 30%-50% (Abizanda et al 2009
; Gabryelewicz et al 2004
; Geda et al 2008
; Lyketsos et al 2002
). However, if item 10 of the GDS was removed from analysis, our results would be more consistent with these previous estimates. As memory problems are not considered to be symptoms of depression by most diagnostic criteria(APA 1994
), we would recommend that when utilizing the GDS to estimate the prevalence of SSD in MCI populations, item 10 should be excluded (Rovner et al 2009
). However, we also recognize that endorsement of this item may in fact represent difficulties with concentration which is a symptom of depression(APA 1994
) and further research may be necessary to determine the validity of this item of the GDS for use in MCI populations. Further, while there is not a consensus criterion for defining SSD, our methodology for designating SSD included individuals with only one reported depressive symptom consistent with many previous studies evaluating neuropsychiatric symptoms in MCI (Abizanda et al 2009
; Gabryelewicz et al 2004
; Lyketsos et al 2002
). However, we do recognize that SSD is also often utilized to denote individuals with two or more depressive symptoms (Judd et al 1994
) (Lyness et al 2009
) a distinction which is particularly important when comparing the prevalence of SSD across different patient populations.
Our findings also suggested that at baseline, individuals with stable MCI do not differ from individuals who progress to dementia with respect to overall severity of SSD or the endorsement of specific items. These findings were unexpected given recent findings that depressive symptom severity and endorsement of specific affective symptoms at baseline differentiated individuals who converted to dementia from cognitively stable MCI participants in other studies (Boyle et al 2010
) (Houde et al 2008
). We interpret our findings to suggest that SSD in MCI, unlike more significant symptoms of depression, are primarily a generalized consequence or concurrent feature of the MCI syndrome but these symptoms are not pathognomic features of individuals at higher risk for dementia. Further, given that the most commonly endorsed SSD in this sample included items that could be attributed to cognitive decline and resulting activity limitations, our results could be interpreted to suggest that SSD in MCI populations does not represent an a concurrent affective component and instead reflects a significant overlap in symptoms between the two syndromes.
When we evaluated the stability of depressive symptoms categorically over time we found that the majority of patients in the sample demonstrated stable, fluctuating, or improvement in SSD with only a relatively small proportion of the sample (16%) exhibiting worsening of SSD. This finding was consistent with previous studies demonstrating that cumulative ratings of depressive symptom severity in MCI are relatively stable over time (Li et al 2001
; Steinberg et al 2004
). However, unexpectedly we did not see significant differences between our two MCI groups with respect to categorical evaluations of stability of total SSD severity as might be expected given a recent study suggesting that increased SSD severity over time represented a risk for dementia (Rovner et al 2009
). Unlike this previous study, however, we utilized categorical ratings of SSD rather than total symptom score, which may have contributed to our divergent findings. We utilized this categorical approach as we felt this represented the most clinically meaningful analysis of the data as by definition SSD represent subthreshold symptoms of depression.
In contrast, our findings indicate that the worsening of four specific items of the GDS (memory problems, dropped activities and interests, preference for staying at home, and feelings of helplessness) over time relative to baseline endorsement were associated with conversion to dementia. As we feel these four items are most strongly associated with cognitive problems and functional limitations which are core aspects of a diagnosis of dementia, these findings are not surprising but do illustrate the complexity of distinguishing mood symptoms from cognitive symptoms among individuals with MCI(Steffens 2008
). However, after accounting for other clinical features, only worsening of memory problems over time was associated with conversion to dementia. Again, as memory problems are not typically viewed as a symptom of depression and represent a core feature of dementia, this finding is not surprising. However, a lack of association between the stability of other SSD that are more reflective of affective symptoms, such as feelings of depressed mood and worthlessness, and conversion to dementia suggests worsening of affective symptoms are not core depressive features of a prodromal phase of incipient dementia.
While we expected memory symptoms to be common in MCI individuals, our findings that 42% of the sample endorsed memory problems is significant for several reasons. First, we expected a higher rate of endorsement for this item given that all participants in the study were diagnosed with MCI and demonstrated memory impairments on testing. Our findings indicate that less than one half of participants in the sample reported an awareness of cognitive symptoms that are core diagnostic features of MCI. Given this, we feel that endorsement of memory problems on the GDS may represent a mechanism for evaluating participant's awareness or insight into cognitive deficits and recent studies have suggested that patient awareness of cognitive symptoms may be a particularly useful in differentiating individuals with different forms neurodegenerative disease (Barnes et al 2006
; Williamson et al 2009
). Our results could extend these previous studies to suggest that awareness of memory problems in MCI, while not typically viewed as SSD, may also be a significant clinical attribute associated with increased risk for conversion to dementia. In addition, previous studies evaluating the agreement between self reported symptoms of depression and informant ratings of depression in MCI and dementia patients have found that item 10 represents the single item of the GDS for which patients and informants show high degrees of agreement(Chopra et al 2008
). In combination, these findings would suggest that self-report measures of awareness of memory problems obtained from commonly utilized measures of depression may be a particularly useful, in combination with measures of cognitive functioning and activity limitations, in identifying individuals at risk for continued cognitive decline.
Overall, this study has several strengths including a large sample size, thorough ascertainment of MCI status, and a relatively long follow up period. Despite these strengths, there are several limitations to the study which also should be discussed. First, it is important to note that for our designation of SSD we did not require specific depressive symptoms to be endorsed and we did not exclude any individual items of the GDS from our statistical analyses. Although our intent for this study was not to validate the short form of the GDS or to demonstrate the incidence of SSD in MCI populations, this methodological consideration will limit the generalizability of our findings. Similarly, diagnostic evaluations of minor depression were not conducted and therefore, it is possible that some of the patients that we designated as exhibiting SSD may have in fact met diagnostic criteria for minor depression. Further, as we excluded participants with major depression and significant cerebrovascular disease, our ability to generalize our findings to the larger population is limited. Additionally, while not specific to our study, measurement error may have resulted in the inclusion of some individuals with normal cognitive function or dementia in our baseline sample or the misdiagnosis of dementia over the 36 interval. Lastly, by design, we utilized only one self-report measure of depression to evaluate SSD. Given previous studies demonstrating that ratings of depressive symptoms in MCI often differ from clinician ratings and informant ratings(Chopra et al 2008
), this represents a further limitation to our findings.