Dataset Information

Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data.

ABSTRACT:

Objective

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).

Method

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.

Results

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 symptoms at follow-up.

Conclusions

Results suggest that identifying early clinically relevant cognitive decline in late middle-age is feasible using robust norms and multi-test criteria.

SUBMITTER: Clark LR

PROVIDER: S-EPMC5088607 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data.

Clark Lindsay R LR Koscik Rebecca L RL Nicholas Christopher R CR Okonkwo Ozioma C OC Engelman Corinne D CD Bratzke Lisa C LC Hogan Kirk J KJ Mueller Kimberly D KD Bendlin Barbara B BB Carlsson Cynthia M CM Asthana Sanjay S Sager Mark A MA Hermann Bruce P BP Johnson Sterling C SC

Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists 20161101 7

<h4>Objective</h4>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).<h4>Method</h4>Robust norms were developed for neuropsychological mea ...[more]

PMID: 27193363

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Project description:BACKGROUND:Studies have suggested associations between self-reported engagement in health behaviors and reduced risk of cognitive decline. Most studies explore these relationships using one health behavior, often cross-sectionally or with dementia as the outcome. In this study, we explored whether several individual self-reported health behaviors were associated with cognitive decline when considered simultaneously, using data from the Wisconsin Registry for Alzheimer's Prevention (WRAP), an Alzheimer's disease risk-enriched cohort who were non-demented and in late midlife at baseline. METHOD:We analyzed longitudinal cognitive data from 828 participants in WRAP, with a mean age at baseline cognitive assessment of 57 (range = 36-78, sd = 6.8) and an average of 6.3 years (standard deviation = 1.9, range = 2-10) of follow-up. The primary outcome was a multi-domain cognitive composite, and secondary outcomes were immediate/delayed memory and executive function composites. Predictors of interest were self-reported measures of physical activity, cognitive activity, adherence to a Mediterranean-style diet (MIND), and interactions with each other and age. We conducted linear mixed effects analyses within an Information-theoretic (IT) model averaging (MA) approach on a set of models including covariates and combinations of these 2- and 3-way interactions. The IT approach was selected due to the large number of interactions of interest and to avoid pitfalls of traditional model selection approaches. RESULTS:Model-averaged results identified no significant self-reported health behavior*age interactions in relationship to the primary composite outcome. In secondary outcomes, higher MIND diet scores associated with slower decline in executive function. Men showed faster decline than women on delayed memory, independent of health behaviors. There were no other significant interactions among any other health behaviors and cognitive trajectories. CONCLUSIONS:When multiple covariates and health behaviors were considered simultaneously, there were limited weak associations with cognitive decline in this age range. These results may be explained alone or in combination by three alternative explanations: 1) the range of cognitive decline is in middle age is too small to observe relationships with health behaviors, 2) the putative associations of these health behaviors on cognition may not be robust in this age range, or 3) the self-reported measures of the health behaviors may not be optimal for predicting cognitive decline. More study may be needed that incorporates sensitive measures of health behaviors, AD biomarker profiles, and/or other disease comorbidities.

Project description:We compared two methods of diagnosing mild cognitive impairment (MCI): conventional Petersen/Winblad criteria as operationalized by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and an actuarial neuropsychological method put forward by Jak and Bondi designed to balance sensitivity and reliability. 1,150 ADNI participants were diagnosed at baseline as cognitively normal (CN) or MCI via ADNI criteria (MCI: n = 846; CN: n = 304) or Jak/Bondi criteria (MCI: n = 401; CN: n = 749), and the two MCI samples were submitted to cluster and discriminant function analyses. Resulting cluster groups were then compared and further examined for APOE allelic frequencies, cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, and clinical outcomes. Results revealed that both criteria produced a mildly impaired Amnestic subtype and a more severely impaired Dysexecutive/Mixed subtype. The neuropsychological Jak/Bondi criteria uniquely yielded a third Impaired Language subtype, whereas conventional Petersen/Winblad ADNI criteria produced a third subtype comprising nearly one-third of the sample that performed within normal limits across the cognitive measures, suggesting this method's susceptibility to false positive diagnoses. MCI participants diagnosed via neuropsychological criteria yielded dissociable cognitive phenotypes, significant CSF AD biomarker associations, more stable diagnoses, and identified greater percentages of participants who progressed to dementia than conventional MCI diagnostic criteria. Importantly, the actuarial neuropsychological method did not produce a subtype that performed within normal limits on the cognitive testing, unlike the conventional diagnostic method. Findings support the need for refinement of MCI diagnoses to incorporate more comprehensive neuropsychological methods, with resulting gains in empirical characterization of specific cognitive phenotypes, biomarker associations, stability of diagnoses, and prediction of progression. Refinement of MCI diagnostic methods may also yield gains in biomarker and clinical trial study findings because of improvements in sample compositions of 'true positive' cases and removal of 'false positive' cases.

Dataset Information

Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data.

Objective

Method

Results

Conclusions

Publications

Mild Cognitive Impairment in Late Middle Age in the Wisconsin Registry for Alzheimer's Prevention Study: Prevalence and Characteristics Using Robust and Standard Neuropsychological Normative Data.

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