Regional amyloid accumulation predicts memory decline in initially cognitively unimpaired individuals.
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ABSTRACT: Introduction
The value of quantitative longitudinal and regional amyloid beta (Aβ) measurements in predicting cognitive decline in initially cognitively unimpaired (CU) individuals remains to be determined.Methods
We selected 133 CU individuals with two or more [11C]Pittsburgh compound B ([11C]PiB) scans and neuropsychological data from Open Access Series of Imaging Studies (OASIS-3). Baseline and annualized distribution volume ratios were computed for a global composite and four regional clusters. The predictive value of Aβ measurements (baseline, slope, and interaction) on longitudinal cognitive performance was examined.Results
Global performance could only be predicted by Aβ burden in an early cluster (precuneus, lateral orbitofrontal, and insula) and the precuneus region of interest (ROI) by itself significantly improved the model. Precuneal Aβ burden was also predictive of immediate and delayed episodic memory performance. In Aβ subjects at baseline (N = 93), lateral orbitofrontal Aβ burden predicted working and semantic memory performance.Discussion
Quantifying longitudinal and regional changes in Aβ can improve the prediction of cognitive functioning in initially CU individuals.
SUBMITTER: Collij LE
PROVIDER: S-EPMC8327468 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Importance:To 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. Objective:To determine whether widowhood status and level of brain ?-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults. Design, Setting, and Participants:In 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 ?-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 Measures:Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite. Results:Of 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 ?-amyloid levels (??=?-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 ?-amyloid levels exhibited steeper cognitive decline (??=?-0.22; 95% CI, -0.42 to -0.03; P?=?.02), indicating both independent and interactive associations of ?-amyloid levels and widowhood with cognition. In a secondary model using dichotomous ?-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high ?-amyloid was nearly 3 times faster than among married participants with high ?-amyloid (widowed, high ?-amyloid: ?, -0.33; 95% CI, -0.46 to -0.19; P?<?.001; married, high ?-amyloid: ?, -0.12; 95% CI, -0.18 to -0.01; P?<?.001). Conclusions and Relevance:In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated ?-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.
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| S-EPMC7656171 | biostudies-literature
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| S-EPMC7086102 | biostudies-literature
Project description:ImportanceClinical guidelines currently recommend against amyloid imaging for cognitively unimpaired persons. The goal of Alzheimer's disease (AD) prevention, together with advances in understanding the pathophysiology of AD, however, has led to trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Assuming the eventual success of such trials, millions of patients will be affected. There is a need to understand the effects of biomarker disclosure on those individuals.DesignThe Study of Knowledge and Reactions to Amyloid Testing (SOKRATES) involved 2 semi-structured telephone interviews with individuals who received amyloid PET scan results as part of screening for research participation. Post-disclosure interviews were conducted at 4 to 12 weeks and again 1 year later. Data were collected from November 5, 2014 to November 30, 2016. Interviews were transcribed and coded in NVivo 12.0.Participants80 adults aged 65 and older: 50 who received "elevated" and 30 who received "not-elevated" amyloid PET scan results.Main outcomesInterviews examined four domains: (1) comprehension of the amyloid PET scan result; (2) implications of the result for sense of self, memory, and future; (3) sharing of results with others; and (4) AD risk-reduction behaviors.ResultsParticipants who received an elevated amyloid PET scan result viewed the result as more serious and sensitive than other medical test results given its unique implications for identity, self-determination, and stigma. In contrast, participants who received a not-elevated amyloid PET scan result described feeling relief and reinterpreted perceived memory impairments as normal aging. Participants with elevated amyloid reported contemplating and making more changes to health behaviors and future plans than their peers with not-elevated amyloid.ConclusionsClinical practice in the diagnosis and treatment of persons with preclinical AD, a stage of the disease defined by the presence of biomarkers in the absence of cognitive impairment, will need to address matters of identity, stigma, and life-planning.
| S-EPMC7018056 | biostudies-literature
Project description:ObjectiveValidation 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.MethodsA 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.ResultsParticipant'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.ConclusionOperationalizing 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.
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