Emergence of Mild Cognitive Impairment in Late Middle-Aged Adults in the Wisconsin Registry for Alzheimer's Prevention (original) (raw)
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Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 2016
Detecting cognitive decline in presymptomatic Alzheimer's disease (AD) and early mild cognitive impairment (MCI) is challenging, but important for treatments targeting AD-related neurodegeneration. The current study aimed to investigate the utility and performance of internally developed robust norms and standard norms in identifying cognitive impairment in late middle-age (baseline age range = 36-68; M = 54). Robust norms were developed for neuropsychological measures based on longitudinally confirmed cognitively normal (CN) participants (n= 476). Seven hundred and seventy-nine participants enriched for AD risk were classified as psychometric MCI (pMCI) or CN based on standard and robust norms and "single-test" versus "multi-test" criteria. Prevalence of pMCI ranged from 3% to 49% depending on the classification scheme used. Those classified as pMCI using robust norms exhibited greater subjective cognitive complaints, diagnostic stability, and mild clinical ...
Frontiers in Aging Neuroscience, 2021
While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants wh...
Journal of the International Neuropsychological Society, 2018
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior expo...
Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging
Neurology, 2015
We sought to develop risk scores for the progression from cognitively normal (CN) to mild cognitive impairment (MCI). We recruited into a longitudinal cohort study a randomly selected, population-based sample of Olmsted County, MN, residents, aged 70 to 89 years on October 1, 2004. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychological measures, and were classified as CN, MCI, or dementia. Using baseline demographic and clinical variables in proportional hazards models, we derived scores that predicted the risk of progressing from CN to MCI. We evaluated the ability of these risk scores to classify participants for MCI risk. Of 1,449 CN participants, 401 (27.7%) developed MCI. A basic model had a C statistic of 0.60 (0.58 for women, 0.62 for men); an augmented model resulted in a C statistic of 0.70 (0.69 for women, 0.71 for men). Both men and women in the highest vs lowest sex-specific quartiles of the augmented model's ...
Clinical Progression of Baseline Risk States for Mild Cognitive Impairment
Journal of Alzheimer's Disease, 2022
Background:This memory-clinic study joins efforts to study earliest clinical signs and symptoms of Alzheimer’s disease and related dementias: subjective reports and objective neuropsychological test performance.Objective:The memory-clinic denoted two clinical “grey zones”: 1) subjective cognitive decline (SCD; n = 107) with normal objective test scores, and 2) isolated low test scores (ILTS; n = 74) without subjective complaints to observe risk for future decline.Methods:Initial and annual follow-up clinical research evaluations and consensus diagnosis were used to evaluate baseline characteristics and clinical progression over 2.7 years, compared to normal controls (NC; n = 117).Results:The ILTS group was on average older than the NC and SCD groups. They had a higher proportion of people identifying as belonging to a minoritized racial group. The SCD group had significantly more years of education than the ILTS group. Both ILTS and SCD groups had increased risk of progression to mild cognitive impairment. Older age, minoritized racial identity, and baseline cognitive classification were risk factors for progression.Conclusion:The two baseline risk groups look different from each other, especially with respect to demographic correlates, but both groups predict faster progression than controls, over and above demographic differences. Varied presentations of early risk are important to recognize and may advance cognitive health equity in aging.
Neuropsychology, 2008
The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up.
Putting the Alzheimer's cognitive test to the test I: Traditional psychometric methods
Alzheimer's & Dementia, 2013
Background: The Alzheimer's Disease Assessment Scale-Cognitive Behavior section (ADAS-Cog) is the most commonly used cognitive test in AD clinical trials. However, there are concerns about its use in early-stage disease. Herein we examine those concerns using traditional psychometric methods. Methods: We analyzed ADAS-Cog data (n 5 675) based on six psychometric properties: data completeness; scaling assumptions; targeting; reliability; validity; and responsiveness. Results: At the scale-level, criteria tested for data completeness, scaling assumptions (item total correlations 0.33-0.59), targeting (no floor/ceiling effects), reliability (Cronbach's a 5 0.74), and validity (correlation with MMSE 5 20.70) were satisfied. Responsiveness (baseline to 12 months; n 5 145) was moderate to high (effect size 5 20.73). However, 8 of 11 ADAS-Cog components had substantial ceiling effects (range 32%-83%), and decreased responsiveness associated with low to moderate effect sizes (0.14-0.65). Conclusion: In our study, many patients with AD found large portions of the ADAS-Cog too easy. Future research should consider modifying the ADAS-Cog or developing a new test.
In 2011, the U.S. National Institute on Aging published guidelines for clinical diagnostics for Alzheimer’s disease dementia. These guidelines define a continuum with three stages—an early, pre-clinical stage with no symptoms, followed by mild cognitive impairment, and a final stage of Alzheimer’s disease dementia. This methodological critique examines the validity of this continuum. No studies exist showing the progression of these biomarkers to Alzheimer’s disease. There is also a lack of empirical evidence showing how biomarkers determine mild cognitive impairment, which has multiple etiologies. The guidelines fail to explain anomalies where there are biomarkers but no expression of Alzheimer’s disease.