Prevalence and Clinical Implications of a β-Amyloid–Negative, Tau-Positive Cerebrospinal Fluid Biomarker Profile in Alzheimer Disease

IMPORTANCE: Knowledge is lacking on the prevalence and prognosis of individuals with a β-amyloid-negative, tau-positive (A-T+) cerebrospinal fluid (CSF) biomarker profile. OBJECTIVE: To estimate the prevalence of a CSF A-T+ biomarker profile and investigate its clinical implications. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of the cross-sectional multicenter University of Gothenburg (UGOT) cohort (November 2019-January 2021), the longitudinal multicenter Alzheimer Disease Neuroimaging Initiative (ADNI) cohort (individuals with mild cognitive impairment [MCI] and no cognitive impairment; September 2005-May 2022), and 2 Wisconsin cohorts, Wisconsin Alzheimer Disease Research Center and Wisconsin Registry for Alzheimer Prevention (WISC; individuals without cognitive impairment; February 2007-November 2020). This was a multicenter study, with data collected from referral centers in clinical routine (UGOT) and research settings (ADNI and WISC). Eligible individuals had 1 lumbar puncture (all cohorts), 2 or more cognitive assessments (ADNI and WISC), and imaging (ADNI only) performed on 2 separate occasions. Data were analyzed on August 2022 to April 2023. EXPOSURES: Baseline CSF Aβ42/40 and phosphorylated tau (p-tau)181; cognitive tests (ADNI: modified preclinical Alzheimer cognitive composite [mPACC]; WISC: modified 3-test PACC [PACC-3]). Exposures in the ADNI cohort included [18F]-florbetapir amyloid positron emission tomography (PET), magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose PET (FDG-PET), and cross-sectional tau-PET (ADNI: [18F]-flortaucipir, WISC: [18F]-MK6240). MAIN OUTCOMES AND MEASURES: Primary outcomes were the prevalence of CSF AT biomarker profiles and continuous longitudinal global cognitive outcome and imaging biomarker trajectories in A-T+ vs A-T- groups. Secondary outcomes included cross-sectional tau-PET. RESULTS: A total of 7679 individuals (mean [SD] age, 71.0 [8.4] years; 4101 male [53%]) were included in the UGOT cohort, 970 individuals (mean [SD] age, 73 [7.0] years; 526 male [54%]) were included in the ADNI cohort, and 519 individuals (mean [SD] age, 60 [7.3] years; 346 female [67%]) were included in the WISC cohort. The prevalence of an A-T+ profile in the UGOT cohort was 4.1% (95% CI, 3.7%-4.6%), being less common than the other patterns. Longitudinally, no significant differences in rates of worsening were observed between A-T+ and A-T- profiles for cognition or imaging biomarkers. Cross-sectionally, A-T+ had similar tau-PET uptake to individuals with an A-T- biomarker profile. CONCLUSION AND RELEVANCE: Results suggest that the CSF A-T+ biomarker profile was found in approximately 5% of lumbar punctures and was not associated with a higher rate of cognitive decline or biomarker signs of disease progression compared with biomarker-negative individuals

Age and extraversion differences in heart rate reactivity during working memory tasks.

Research and theory have shown a link between heart rate reactivity during cognitive testing and extraversion in younger adults; however, similar work has not been conducted with older adults. This study was designed to explore age and extraversion-related differences in within-person heart rate (HR) reactivity during two working memory tasks of varying difficulty using a multi-level modeling approach. Across 570 total within-person assessments of continuous HR monitoring, 28 younger adults (M = 19.76, SD = 1.15) and 29 older adults (M = 71.19, SD = 6.63) were administered two working memory tasks (backward digit span and n-back). There were no age differences in reactivity during the backward digit span. However, similar to previous findings, on the more difficult n-back task, younger adults low in extraversion showed a trend toward higher HR reactivity than young adults high in extraversion. Interestingly, the older adults showed the opposite pattern in that lower extraversion older adults were less reactive than the higher extraversion older adults who showed the steepest increase in HR. The HR increase of the older adults high in extraversion may be an indication of higher engagement in this more difficult task. Individual differences in extraversion need to be taken into account when administering working memory tasks in older adults

Information search and decision making: Effects of age and complexity on strategy use.

The impact of task complexity on information search strategy and decision quality was examined in a sample of 135 young, middle-aged, and older adults. We were particularly interested in the competing roles of fluid cognitive ability and domain knowledge and experience, with the former being a negative influence and the latter being a positive influence on older adults ’ performance. Participants utilized 2 decision matrices, which varied in complexity, regarding a consumer purchase. Using process tracing software and an algorithm developed to assess decision strategy, we recorded search behavior, strategy selection, and final decision. Contrary to expectations, older adults were not more likely than the younger age groups to engage in information-minimizing search behaviors in response to increases in task complexity. Similarly, adults of all ages used comparable decision strategies and adapted their strategies to the demands of the task. We also examined decision outcomes in relation to participants ’ preferences. Overall, it seems that older adults utilize simpler sets of information primarily reflecting the most valued attributes in making their choice. The results of this study suggest that older adults are adaptive in their approach to decision making and that this ability may benefit from accrued knowledge and experience