Dataset Information

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

ABSTRACT:

Objective

Validation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed "neuropsychological (NP) decline," in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.

Methods

A prospective cohort study utilized 6,794 older adults from the National Alzheimer's Coordinating Center (NACC) database with a baseline diagnosis of normal cognition, impaired without MCI or with MCI. Operationalization of NP decline over 12-month follow-up used regression-based norms developed in a robustly normal reference sample. The extent to which each participant's 12-month follow-up score deviated from norm-referenced expectations was quantified and standardized to an NP decline z-score. Cox regression evaluated whether the NP decline metric predicted future dementia.

Results

Participant's NP decline scores predicted future all-cause dementia in the total sample, χ² = 110.71, hazard ratio (HR) = 1.989, p < 0.001, and in the subset diagnosed with normal cognition, χ² = 40.84, HR = 2.006, p < 0.001, impaired without MCI diagnosis, χ² = 14.89, HR = 2.465, p < 0.001, and impaired with MCI diagnosis, χ² = 55.78, HR = 1.916, p < 0.001.

Conclusion

Operationalizing NP decline over 12 months with a regression-based norming method allows for further stratification of dementia risk along the cognitively unimpaired-to-MCI spectrum. The use of NP decline as an adjunctive marker of risk beyond standard cognitive diagnostic practices may aid in prognosis and clinical decision-making.

SUBMITTER: Ho JK

PROVIDER: S-EPMC9339652 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

Ho Jean K JK Nation Daniel A DA

Frontiers in aging neuroscience 20220718

<h4>Objective</h4>Validation and widespread use of markers indicating decline in serial neuropsychological exams has remained elusive despite potential value in prognostic and treatment decision-making. This study aimed to operationalize neuropsychological decline, termed "neuropsychological (NP) decline," in older adults followed over 12 months in order to aid in the stratification of dementia risk along the cognitively unimpaired-to-mild cognitive impairment (MCI) spectrum.<h4>Methods</h4>A pr ...[more]

PMID: 35923551

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Project description:ImportanceTo reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults.ObjectiveTo determine whether widowhood status and level of brain β-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults.Design, setting, and participantsIn this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical β-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019.Main outcomes and measuresCognitive performance was measured using the Preclinical Alzheimer Cognitive Composite.ResultsOf the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and β-amyloid levels (β = -0.11; 95% CI, -0.19 to -0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline β-amyloid levels exhibited steeper cognitive decline (β = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of β-amyloid levels and widowhood with cognition. In a secondary model using dichotomous β-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid (widowed, high β-amyloid: β, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high β-amyloid: β, -0.12; 95% CI, -0.18 to -0.01; P < .001).Conclusions and relevanceIn a sample of cognitively unimpaired older adults, being widowed was associated with accelerated β-amyloid-related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.

Project description:BackgroundWhat combination of risk factors for Alzheimer's disease (AD) are most predictive of cognitive decline in cognitively unimpaired individuals remains largely unclear. We studied associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-β pathology and decline in cognitive functioning over time in a large sample of cognitively unimpaired older individuals.MethodsWe included 276 cognitively unimpaired older individuals (75 ± 10 years, 63% female) from the EMIF-AD PreclinAD cohort. An AD-PRS was calculated including 83 genome-wide significant variants. The APOE gene was not included in the PRS and was analyzed separately. Baseline amyloid-β status was assessed by visual read of [18F]flutemetamol-PET standardized uptake value images. At baseline and follow-up (2.0 ± 0.4 years), the cognitive domains of memory, attention, executive function, and language were measured. We used generalized estimating equations corrected for age, sex and center to examine associations between APOE genotype and AD-PRS with amyloid-β status. Linear mixed models corrected for age, sex, center and education were used to examine associations between APOE genotype, AD-PRS and amyloid-β status, and their interaction on changes in cognitive functioning over time.ResultsFifty-two participants (19%) had abnormal amyloid-β, and 84 participants (31%) carried at least one APOE ε4 allele. APOE genotype and AD-PRS were both associated with abnormal amyloid-β status. Increasingly more risk-full APOE genotype, a high AD-PRS and an abnormal amyloid-β status were associated with steeper decline in memory functioning in separate models (all p ≤ 0.02). A model including 4-way interaction term (APOE×AD-PRS×amyloid-β×time) was not significant. When modelled together, both APOE genotype and AD-PRS predicted steeper decline in memory functioning (APOE β(SE)=-0.05(0.02); AD-PRS β(SE)=-0.04(0.01)). Additionally, when modelled together, both amyloid-β status and AD-PRS predicted a steeper decline in memory functioning (amyloid-β β(SE)=-0.07(0.04); AD-PRS β(SE)=-0.04(0.01)). Modelling both APOE genotype and amyloid-β status, we observed an interaction, in which APOE genotype was related to steeper decline in memory and language functioning in amyloid-β abnormal individuals only (β(SE)=-0.13(0.06); β(SE)=-0.22(0.07), respectively).ConclusionOur results suggest that APOE genotype is related to steeper decline in memory and language functioning in individuals with abnormal amyloid-β only. Furthermore, independent of amyloid-β status other genetic risk variants contribute to memory decline in initially cognitively unimpaired older individuals.

Dataset Information

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

Objective

Methods

Results

Conclusion

Publications

Neuropsychological Decline Stratifies Dementia Risk in Cognitively Unimpaired and Impaired Older Adults.

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