Longitudinal stability of subsyndromal symptoms of depression in individuals with mild cognitive impairment: Relationship to conversion to dementia after 3years
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.
Available from: Holly D Soares
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ABSTRACT: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; (6) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Multimodal methods incorporating APOE status and longitudinal MRI proved most highly predictive of future decline. Refinements of clinical tests used as outcome measures such as clinical dementia rating-sum of boxes further reduced sample sizes; (7) the pioneering of genome-wide association studies that leverage quantitative imaging and biomarker phenotypes, including longitudinal data, to confirm recently identified loci, CR1, CLU, and PICALM and to identify novel AD risk loci; (8) worldwide impact through the establishment of ADNI-like programs in Japan, Australia, Argentina, Taiwan, China, Korea, Europe, and Italy; (9) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker and clinical data to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (10) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world.
Published by Elsevier Inc.
Available from: Nir Giladi
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ABSTRACT: To study the association of subjective memory complaints (SMC) with affective state and cognitive performance in elders.
We studied community dwelling elderly persons with normal physical examination. Participants completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression Scale (GDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Depending on their answers to the question about their memory condition, participants were divided into complainers and non-complainers and to five groups according to their MMSE scores. These data have been compared to objective cognitive performance according to Mindstreams - a computerized neuropsychological battery. A logistic regression was performed to evaluate odds ratios (OR) and 95% confidence intervals (CI) for those factors, which were associated with SMС (dependent variable).
Of 636 consecutive subjects (61% females), 507 participants (79.7%) had SMС. Presence of SMC was inversely correlated with MMSE scores, (r = −0.108; P for trend = 0.007). GDS and STAI scores were higher among subjects with SMC (OR = 1.23: CI 95%: 1.1–1.36 and OR = 1.03: CI 95%: 1.01–1.07, respectively). SMC did not correlate with objective cognitive performance measured by Mindstreams.
Subjective memory complaints are associated with sub-syndromal depression and anxiety in healthy cognitively normal elders.
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Few studies report incidence of mild cognitive impairment (MCI) and other mild cognitive disorders (MCD) in cohorts in their 60s, at an age when diagnoses are less stable. The authors' goal was to estimate the incidence and prevalence of MCI and MCD, characterize subgroups with stable vs nonstable diagnoses, and evaluate the impact of diagnosis on daily life in a young-old cohort.
A community-based cohort age 60 to 64 years in 1999 (n = 2551) was monitored for 8 years and assessed every 4 years. A two-stage sampling design was used to identify MCI and MCD through a neuropsychological and neurological assessment. A panel of physicians blind to previous diagnoses reviewed each case using published criteria.
The prevalence of MCDs in the cohort aged 68 to 72 years at the last follow-up was approximately 10%. An estimated 141 subjects (7.7%) progressed to MCI and 183 subjects (10.0%) progressed to MCD between years 4 and 8. Only eight participants received a dementia diagnosis at any wave, five of whom progressed from MCDs. More than 45% of diagnoses were unstable during the 8 years of follow-up. Stable diagnoses were associated with lower Mini-Mental State Examination scores, history of neurological disorder, higher cardiovascular risk, and depression at baseline. MCDs were associated with impairments in instrumental activities of daily living and higher rates of reporting memory problems prior to diagnosis.
MCDs in individuals in their 60s occur in at least 10% of the population and are likely to be heterogeneous in terms of their etiology and long-term prognosis, but may cause a significant impact in everyday life.
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