Dataset Information

Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses.

ABSTRACT:

Background

A clinical diagnosis of cognitive impairment is traditionally based on a single cognitive exam, but serial cognitive testing can be sensitive to subtle cognitive changes in asymptomatic individuals and inform cognitive trajectory.

Objective

We evaluated the prognostic utility of identifying longitudinal neuropsychological decline along with single cognitive exam and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in predicting dementia. We also examined brain volumetric differences based on decline trajectories.

Method

Regression models quantified 12-month neuropsychological decline relative to normative expectations among non-demented older adults (N?=?1,074). Progression to dementia over follow-up (18-120 months) was diagnosed using independent modes of assessment.

Results

In Cox regression models controlling for age, sex, education, apolipoprotein E4, and baseline cognitive diagnosis, neuropsychological decline predicted increased dementia risk, ?2?=?69.861, p?ConclusionsLongitudinal diagnosis of neuropsychological decline improved prognostic accuracy beyond single cognitive exam diagnoses and AD CSF biomarkers, even in asymptomatic older adults. Older adults with a trajectory of neuropsychological decline exhibit smaller medial temporal and hippocampal brain volume. Longitudinal diagnostic approaches may benefit selection and randomization procedures for AD clinical trials in asymptomatic individuals.

SUBMITTER: Nation DA

PROVIDER: S-EPMC6598015 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses.

Nation Daniel A DA Ho Jean K JK Dutt Shubir S Han S Duke SD Lai Mark H C MHC

Journal of Alzheimer's disease : JAD 20190101 4

<h4>Background</h4>A clinical diagnosis of cognitive impairment is traditionally based on a single cognitive exam, but serial cognitive testing can be sensitive to subtle cognitive changes in asymptomatic individuals and inform cognitive trajectory.<h4>Objective</h4>We evaluated the prognostic utility of identifying longitudinal neuropsychological decline along with single cognitive exam and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in predicting dementia. We also examined br ...[more]

PMID: 31104015

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Project description:BackgroundLeukotriene receptor antagonists (LTRAs) alleviate Alzheimer's disease (AD) pathology and improve cognition in animal models; however, clinical evidence is limited. This study aimed to explore the associations between the use of LTRAs (montelukast or zafirlukast) and cognitive performance in people with normal cognition, mild cognitive impairment (MCI), or AD dementia. We hypothesized that LTRA use would be associated with better cognitive performance over time.MethodsThis longitudinal observational study used data from the National Alzheimer's Coordinating Center. Within groups of participants with normal cognition, MCI, or AD dementia, LTRA users were matched 1:3 to non-users using propensity score matching. Cognitive domains including immediate and delayed memory (Wechsler Memory Scale Revised-Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol Substitution Test), and language (animal naming, vegetable naming, and Boston Naming Test) were compared between users and non-users in mixed-effects linear or Poisson regression models.ResultsIn AD dementia, LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol Substitution Test (Β = 1.466 [0.253, 2.678] symbols/year, n = 442), and language, as measured by animal naming (Β = 0.541 [0.215, 0.866] animals/year, n = 566), vegetable naming (B = 0.309 [0.056, 0.561] vegetables/year, n = 565), and the Boston Naming Test (B = 0.529 [0.005, 1.053] items/year, n = 561). Effect sizes were small but persisted after controlling for a 10% false discovery rate. LTRA use was not associated with changes in memory performance in AD, nor was it associated with changes in cognitive performance in people with normal cognition or MCI. In a post hoc analysis, LTRA use was associated with a slower decline in clinical progression in MCI (B = -0.200 [-0.380, -0.019] points/year, n = 800) and AD dementia (B = -0.321 [-0.597, -0.046] points/year, n = 604) as measured by CDR Sum of Boxes.ConclusionsThe use of LTRAs was associated with preserved function in non-amnestic cognitive domains in AD dementia. The role of leukotrienes and their receptors in cognitive decline warrants further investigation and the leukotriene pathway may represent a target for AD treatment.

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Dataset Information

Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses.

Background

Objective

Method

Results

Publications

Neuropsychological Decline Improves Prediction of Dementia Beyond Alzheimer's Disease Biomarker and Mild Cognitive Impairment Diagnoses.

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