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| Principal Investigator | |
| Principal Investigator's Name: | JEE WOOK KIM |
| Institution: | Hallym University Dongtan Sacred Heart Hospital |
| Department: | Neuropsychiatry |
| Country: | |
| Proposed Analysis: | Subjective memory complaint (SMC) is very common in elderly individuals.1 Its prevalence found in several community-based studies2-6 varies from approximately 25% to over 50%, and more than half of elderly with SMC were worried about incipient dementia, in particular, Alzheimer's disease (AD) dementia.7,8 In spite of these high prevalence and concerns, SMC has been poorly understood symptom or condition. There are controversies on whether SMC were considered merely as normal age-related process9 or not. Over the last few decades, several cross-sectional studies5,10,11 have reported that SMC were more often related to a depression than to poor performance on objective cognitive tests. Furthermore, age, gender, level of education, vascular burdens, Apolipoprotein E (ApoE) ε4, and executive dysfunction correlated with anosognosia (poor awareness of illness) were also known as risk or confounding factors associated with SMC.1,10-15 However, increasing reports of recent longitudinal studies16-19 suggested that SMC may be an earlier manifestation of pathologic process in AD dementia than mild cognitive impairment (MCI).20 Since AD pathologic process in the brain evolve several years before the onset of MCI, subjective perception of specific experienced memory impairment different from cognitively normal (CN) ageing may cause SMC with specific form in a pre-MCI stage of subsequently manifest AD dementia.21 Furthermore, in the earliest AD stage, increased compensatory neuronal effect probably related to SMC may facilitate still normal performance on objective cognitive tests.22 There are a variety of positive results for screening or prediction of cognitive decline from elderly subjects with SMC according to various assessments of SMC (question number: one,10,17,23 two, or three and above items23,24; answer number per one question: two,23,24 three,17 four10; type: global,17,23,24 specific,23,24 associated with worry17), target end point (AD10,17, dementia23,24), difference of study designs (cross-sectional,23,24 longitudinal10,17), cognition level of subjects [at baseline] (CN,10,17 MCI,17 and non-dementia17,23,24), presence of adjusting risk or confounding factors associated with SMC (depression,10,17 age,10,17 gender,10,17 level of education,10,17,23 vascular burdens, ApoE ε4,17 and executive dysfunction). It is very important to define an earlier at risk stage for AD for early identification and treatment of AD25 in cost-effective aspects.26 On this view, the extensions of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), i.e., ADNI go and ADNI 2, have introduced the distinction of MCI into early MCI (EMCI) and late MCI (LMCI). LMCI refers to the original definition of MCI (performance of below 1.5 standard deviations [SD] of age-, gender-, and education-adjusted normative mean on a standard test), while impairment in EMCI is defined as performance between 1.0 SD and 1.5 SD below the normative mean.27 Longitudinal follow-up of MCI (i.e., LMCI) elderly individuals showed a higher progression to probable AD dementia at a rate of 10 to 15% per year relative to normal elderly subjects at a rate of 1 to 2%.28 One prospective cohort study also showed that risk of AD dementia was greatest in LMCI relative to other non-demented individuals (either CN or EMCI).17 The mini-mental state exam (MMSE)29 has become a widely used objective cognitive screening test for AD dementia in both clinical and research settings. Indeed, MMSE has been useful cognitive test ranging from examining cutoff scores for differentiation from AD dementia30 to examining prediction of incident AD dementia in non-demented individuals.31 However, MMSE has poor sensitivity in MCI screening32 and little is known about screening accuracy difference between SMC and MMSE in MCI screening. Taken together, although it has been shown that SMC contribute independently to AD dementia screening or prediction as well as MMSE, these study raise important questions whether SMC could have more excellent screening accuracy for late MCI (i.e., high risk state for the development of AD dementia) and comparable one for early AD dementia relative to MMSE from CN elderly individuals. The study aimed to clarify whether SMC increase the risk of late MCI or early AD dementia, and whether the screening accuracy of SMC for late MCI or early AD dementia from CN is higher or not relative to MMSE. Statistical Analysis Diagnostic group differences of subjects’ characteristics were examined by analysis of variation (ANOVA) with post hoc contrasts using Turkey methods. Categorical variables were compared using 2 test or Fisher exact test. The subjects’ characteristics between SMC-O positive and negative group were done by Student t test or 2. Logistic regression analysis was performed to assess risk of cognitive status [CN versus late MCI (or early AD)] according to SMC-O adjusting for potential confounding variables. A series of multiple logistic regression models for late MCI and early AD screening were used to obtain new scores of SCM-O and MMSE after adjusting potential confounding variables. Receiver operating characteristic (ROC) curve analysis was used to compare late MCI and early AD screening accuracy between the new scores of SCM-O and MMSE derived from logistic regression models. Area under the curve (AUC) of ROC curve was compared by using the method of Hanley and McNeil.50 The level of statistical significance was set as two-tailed p < 0.05. ROC curve analyses were performed by using MedCalc for Windows, version 12.1 (MedCalc Software, Mariakerke, Belgium). All the other analyses except ROC curve analysis were performed by using SPSS software, version 15.0 (SPSS Inc, Chicago, IL). |
| Additional Investigators |
