Longitudinal stability of subsyndromal symptoms of depression in individuals with mild cognitive impairment: relationship to conversion to dementia after 3 years
ABSTRACT To evaluate the degree to which longitudinal stability of subsyndromal symptoms of depression (SSD) is associated with conversion to dementia in patients with mild cognitive impairment (MCI).
Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and 12-month intervals over 3 years. Participants were designated as MCI converters if dementia was diagnosed within 3 years or as cognitively stable MCI if dementia was not diagnosed during this interval. SSD were evaluated utilizing the 15-item Geriatric Depression Scale (GDS). Endorsement of specific SSD at baseline and the stability of SSD over 36 months were compared between the two MCI groups.
Baseline symptom endorsement and stability of total GDS scores did not differentiate MCI groups. Worsening of four individual items from the GDS over time (memory problems, feelings of helplessness, loss of interest, and preference for staying at home) differentiated MCI converters from cognitively stable MCI (p < 0.05 for all). However, only increased endorsement of memory symptoms over time was associated with progression to dementia after controlling for other clinical variables (p = 0.05).
SSD in MCI participants largely consist of cognitive symptoms and activity limitations, and the stability of SSD over time differentiated the MCI groups better than baseline endorsement of symptoms. However, the only significant predictor of conversion to dementia was increased endorsement of memory problems, which likely represents insight into cognitive problems more than depressive symptomatology in MCI individuals.
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ABSTRACT: Introduction: Longitudinal assessment of cognitive decline in amnestic mild cognitive impairment (aMCI) and Alzheimer?s disease (AD) often involves the use of both informant-based and objective cognitive assessments. As efforts have focused on identifying individuals in pre-clinical stages, instruments that are sensitive to subtle cognitive changes are needed. The Alzheimer?s Questionnaire (AQ) has demonstrated high sensitivity and specificity in identifying aMCI and AD; however its ability to measure longitudinal change has not been assessed. The aims of this study are to assess the sensitivity to change of the AQ and to determine whether the AQ predicts change in global cognition and function in cognitively normal (CN), aMCI, and AD subjects. Methods: Data from 202 individuals participating in a brain and body donation program were utilized for this study (101 CN, 62 aMCI, 39?AD). AD and aMCI individuals were matched on age, education, and gender to CN individuals. Sensitivity to change of the AQ was assessed in addition to the AQ?s ability to predict change in global cognition and function. The Mini Mental State Exam (MMSE) and Functional Activities Questionnaire (FAQ) were used as gold standard comparisons of cognition and function. Sample size calculations for a 25% treatment effect were also carried out for all three groups. Results: The AQ demonstrated small sensitivity to change in the aMCI and CN groups (d=0.33, d=0.23, respectively) and moderate sensitivity to change in the AD group (d=0.43). The AQ was associated with increases in the Clinical Dementia Rating Global Score (OR=1.20 (1.09, 1.32), P <0.001). Sample size calculations found that the AQ would require substantially fewer subjects than the MMSE given a 25% treatment effect. Conclusions: Although the AQ demonstrated small sensitivity to change in aMCI and CN individuals in terms of effect size, the AQ may be superior to objective cognitive tests in terms of required sample size for a clinical trial. As clinicians and researchers continue to identify and treat individuals in earlier stages of AD, there is a need for instruments that are sensitive to cognitive changes in these earlier stages.Alzheimer's Research and Therapy 01/2015; 7(1). DOI:10.1186/s13195-014-0092-z · 3.50 Impact Factor
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ABSTRACT: Objective: Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition. Method: The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies. Results: There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies. Conclusions: Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.American Journal of Psychiatry 02/2015; DOI:10.1176/appi.ajp.2014.14070878 · 13.56 Impact Factor
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ABSTRACT: The updated diagnostic criteria for Alzheimer's disease (AD) distinguish three stages: dementia, symptomatic pre-dementia [i.e. mild cognitive impairment (MCI)], and asymptomatic pre-dementia. Although AD is primarily associated with cognitive deficits, co-morbid depressive symptoms frequently occur at each stage. Depression in AD dementia is qualitatively different from depression in cognitively intact and/or younger populations, and may be less responsive to established interventions. In MCI, depressive symptoms are associated with higher rates of progression to dementia, and may identify a subset of individuals that are more responsive to acetylcholinesterase inhibitor treatment. Clinical and subsyndromal depressive symptoms in cognitively normal elderly represent a risk factor and/or prodrome for dementia due to AD, but sustained antidepressant therapy may be able to modulate this risk.04/2013; 3(2):147-155. DOI:10.2217/nmt.13.10