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

Importance: Knowledge is lacking on the prevalence and prognosis of individuals with a ß-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 Aß42/40 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.

Large-scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease.

INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest. METHODS: We conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation. RESULTS: We identified 61 proteins significantly associated with the AT category (P < 5.46 × 10-5 ) and 636 significant protein-biomarker associations (P < 6.07 × 10-6 ). Proteins from glucose and carbon metabolism pathways were enriched among amyloid- and tau-associated proteins, including malate dehydrogenase and aldolase A, whose associations with tau were replicated in an independent cohort (n = 717). CSF metabolomics identified and replicated an association of succinylcarnitine with phosphorylated tau and other biomarkers. DISCUSSION: These results implicate glucose and carbon metabolic dysregulation and increased CSF succinylcarnitine levels with amyloid and tau pathology in AD. HIGHLIGHTS: Cerebrospinal fluid (CSF) proteome enriched for extracellular, neuronal, immune, and protein processing. Glucose/carbon metabolic pathways enriched among amyloid/tau-associated proteins. Key glucose/carbon metabolism protein associations independently replicated. CSF proteome outperformed other omics data in predicting amyloid/tau positivity. CSF metabolomics identified and replicated a succinylcarnitine-phosphorylated tau association.

Associations between self-reported sleep patterns and health, cognition and amyloid measures: results from the Wisconsin Registry for Alzheimer's Prevention.

Previous studies suggest associations between self-reported sleep problems and poorer health, cognition, Alzheimer's disease pathology and dementia-related outcomes. It is important to develop a deeper understanding of the relationship between these complications and sleep disturbance, a modifiable risk factor, in late midlife, a time when Alzheimer's disease pathology may be accruing. The objectives of this study included application of unsupervised machine learning procedures to identify distinct subgroups of persons with problematic sleep and the association of these subgroups with concurrent measures of mental and physical health, cognition and PET-identified amyloid. Dementia-free participants from the Wisconsin Registry for Alzheimer's Prevention (n = 619) completed sleep questionnaires including the Insomnia Severity Index, Epworth Sleepiness Scale and Medical Outcomes Study Sleep Scale. K-means clustering analysis identified discrete sleep problem groups who were then compared across concurrent health outcomes (e.g. depression, self-rated health and insulin resistance), cognitive composite indices including episodic memory and executive function and, in a subset, Pittsburgh Compound B PET imaging to assess amyloid burden. Significant omnibus tests (P < 0.05) were followed with pairwise comparisons. Mean (SD) sample baseline sleep assessment age was 62.6 (6.7). Cluster analysis identified three groups: healthy sleepers [n = 262 (42.3%)], intermediate sleepers [n = 229 (37.0%)] and poor sleepers [n = 128 (20.7%)]. All omnibus tests comparing demographics and health measures across sleep groups were significant except for age, sex and apolipoprotein E e4 carriers; the poor sleepers group was worse than one or both of the other groups on all other measures, including measures of depression, self-reported health and memory complaints. The poor sleepers group had higher average body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance. After adjusting for covariates, the poor sleepers group also performed worse on all concurrent cognitive composites except working memory. There were no differences between sleep groups on PET-based measures of amyloid. Sensitivity analyses indicated that while different clustering approaches resulted in different group assignments for some (predominantly the intermediate group), between-group patterns in outcomes were consistent. In conclusion, distinct sleep characteristics groups were identified with a sizable minority (20.7%) exhibiting poor sleep characteristics, and this group also exhibited the poorest concurrent mental and physical health and cognition, indicating substantial multi-morbidity; sleep group was not associated with amyloid PET estimates. Precision-based management of sleep and related factors may provide an opportunity for early intervention that could serve to delay or prevent clinical impairment.

The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults.

BACKGROUND: Insulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer's clinical syndrome in epidemiologic studies but have not been associated with tau tangles in neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships. METHODS: Participants were enrolled in either the Wisconsin Registry for Alzheimer's Prevention (WRAP) or Wisconsin Alzheimer's Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR (n=280 WRAP participants) and a sample characterized on diabetic status (n=285 WRAP and n=109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand 18F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status. RESULTS: Neither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic (n=6) relative to the nondiabetic group (n=88). CONCLUSION: Findings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.

Effect of Metabolic Syndrome Risk Factors on Processing Speed and Executive Function in Three Racialized Groups.

BACKGROUND: Metabolic syndrome (MetS) has been associated with increased risk for Alzheimer's disease and related dementias (ADRD). Understanding the association of MetS risk factors to processing speed and executive function in the pre-clinical stages of ADRD in under-represented groups would offer insight on potential mechanisms through which MetS associates with ADRD risk. OBJECTIVE: Examine association of MetS features and processing speed and executive function across three racial groups. METHODS: Cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Disease Prevention completed blood-draws and neuropsychological testing. Six cognitive outcomes were assessed in association to MetS risk factors: Trailmaking Tests A and B, Animal Fluency, Digit Symbol, and composite scores for Processing Speed and Executive Function. Linear mixed effect models were used to assess the relationship between MetS risk factor count and longitudinal cognitive performance across three racialized groups. RESULTS: Participant sample sizes varied by outcome analyzed (N = 714-1,088). African American and Native American groups exhibited higher rates of MetS than non-Hispanic Whites. MetS was associated with processing speed and executive function across all racialized groups. Three-way interaction by racialized group was limited to one cognitive outcome: Trailmaking Test A. CONCLUSION: Metabolic dysfunction incrementally affects cognitive trajectory, with generally similar associations across racial groups. Since racialized groups exhibit higher levels of both MetS and ADRD, MetS may represent a driving factor for increased ADRD risk experience by racialized group and an important and modifiable target through which to reduce risk of ADRD.

Insulin resistance is related to cognitive decline but not change in CSF biomarkers of Alzheimer's disease in non-demented adults.

INTRODUCTION: We investigated whether insulin resistance (IR) was associated with longitudinal age-related change in cognition and biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration in middle-aged and older adults who were non-demented at baseline. METHODS: IR was measured with homeostatic model assessment of insulin resistance (HOMA2-IR). Core AD-related cerebrospinal fluid (CSF) biomarkers and cognition were assessed, respectively, on n = 212 (1 to 5 visits) and n = 1299 (1 to 6 visits). Linear mixed models tested whether HOMA2-IR moderated age-related change in CSF biomarkers and cognition. Linear regressions tested whether HOMA2-IR x apolipoprotein E ε4 allele (APOE ε4) carrier status predicted amyloid beta [Aß] chronicity (estimated duration of amyloid positron emission tomography [PET] positivity) (n = 253). RESULTS: Higher HOMA2-IR was associated with greater cognitive decline but not with changes in CSF biomarkers. HOMA2-IR x APOE4 was not related to Aß chronicity but was significantly associated with CSF phosphorylated tau (P-tau)181/Aß42 level. DISCUSSION: In non-demented adults IR may not be directly associated with age-related change in AD biomarkers. Additional research is needed to determine mechanisms linking IR to cognitive decline.

The relationship of glucose-stimulated insulin secretion to cerebral glucose metabolism and cognition in healthy middle-aged and older adults.

Insulin resistance (IR) has been related to reduced cerebral glucose metabolism in regions identified as hypometabolic in Alzheimer's clinical syndrome. Insulin secretion (IS) has been less studied than IR despite findings that decreased IS is an early indicator of future type 2 diabetes and a potential predictor of Alzheimer's clinical syndrome. We investigated whether higher IR and lower IS would be associated with greater age-related reductions in regional cerebral glucose metabolism and worse cognitive performance. Two-hour oral glucose tolerance testing and 18F-fluorodeoxyglucose positron emission tomography were performed on 1-2 occasions on a sample of healthy middle-aged and older adults from the Wisconsin Alzheimer's Disease Research Center. Neuropsychological tests were completed during Alzheimer's Disease Research Center Clinical Core visits. Pattern of findings suggested that lower (not higher) IS was related to higher regional cerebral glucose metabolism in middle aged but not older adults, and lower (not higher) IS was also related to better immediate recall. In the context of healthy insulin sensitivity, lower IS may be beneficial to brain health.

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.

Prediabetes and working memory in older adults.

Insulin sensitivity, pancreatic ß-cell function, fasting glucose, and 2-h post-load glucose were related to cognition in cognitively healthy nondiabetic older adults. Thirty-five adults (⩾65 years) underwent a 2-h oral glucose tolerance test and cognitive testing. Seventeen had normal glucose tolerance and 18 had intermediate hyperglycaemia or prediabetes (World Health Organization criteria). Fasting glucose and 2-h post-load glucose and oral glucose tolerance test-derived measures of ß-cell function (oral disposition index) and insulin sensitivity were analysed as predictors of four cognitive domains: verbal episodic memory, verbal fluency, executive function, and working memory. The prediabetes group had significantly worse working memory performance than the normal glucose tolerance group. Controlling for age and education, decreased oral disposition index, and increased 2-h post-load glucose were significantly related to worse working memory performance. Prediabetes may worsen working memory in healthy older adults. Reduced pancreatic ß-cell function should be investigated as a contributor to age-related cognitive decline.

Cortisol relates to regional limbic system structure in older but not younger adults.

We investigated if the relationship between age and regional limbic system brain structure would be moderated by diurnal cortisol output and diurnal cortisol slope. Participants aged 23-83 years collected seven salivary cortisol samples each day for 10 consecutive days and underwent magnetic resonance imaging. Age, sex, cortisol, and an age x cortisol interaction were tested as predictors of hippocampal and amygdalar volume and caudal and rostral anterior cingulate cortex (ACC) thickness. We found significant interactions between age and cortisol on left and right amygdalar volumes and right caudal ACC thickness. Older adults with higher cortisol output had smaller left and right amygdalar volumes than older adults with lower cortisol output and younger adults with higher cortisol output. Older and younger adults with lower cortisol output had similar amygdalar volumes. Older adults with a steeper decline in diurnal cortisol had a thicker right caudal ACC than younger adults with a similarly shaped cortisol slope. Hippocampal volume was not related to either cortisol slope or output, nor was pallidum volume which was assessed as an extra-limbic control region. Results suggest that subtle differences in cortisol output are related to differences in limbic system structure in older but not younger adults.

Long-term cortisol measures predict Alzheimer disease risk.

OBJECTIVE: To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. METHOD: We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. RESULTS: UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. CONCLUSIONS: Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD.

The cortisol awakening response and cognition across the adult lifespan.

Although the hippocampus is thought to play a central role in the regulation of the cortisol awakening response (CAR), results from past studies examining the relationship between the CAR and hippocampal-mediated memory and cognition have been mixed. Inconsistent findings may be due to the use of cortisol samples collected on only 1-2days since reduced sampling can permit unstable situational factors to bias results. We used cortisol assessments from 10 consecutive days to test the relationship of the CAR to episodic memory, working memory, and processing speed in a sample of healthy young, middle-aged, and older adults (age range: 23-79years; N=56). We tested if the relationship between the CAR and cognition would depend upon age and also tested if other cortisol measures, specifically waking cortisol, diurnal cortisol output (i.e., area under the curve) and diurnal cortisol slope (linear and quadratic), would be related to cognition. We found that a more positive CAR slope was related to better episodic memory and that this relationship did not depend upon age. The CAR was not significantly related to working memory. The relationship of the CAR to processing speed was not significant when using a CAR measure that corrected for non-compliant cortisol sampling. We also found that higher waking cortisol was significantly related to better working memory, but not episodic memory or processing speed. Neither diurnal cortisol output nor diurnal linear cortisol slope was significantly related to cognitive functioning. Future work should investigate the mechanisms underpinning the relationship of the cortisol awakening process to cognitive functioning.

Solving Tomorrow's Problems Today? Daily Anticipatory Coping and Reactivity to Daily Stressors.

OBJECTIVES: The present study examined the day-to-day fluctuation of state-like anticipatory coping (coping employed prior to stressors) and how these coping processes relate to important outcomes for older adults (i.e., physical health, affect, memory failures). METHOD: Forty-three older adults aged 60-96 (M = 74.65, SD = 8.19) participated in an 8-day daily diary study of anticipatory coping, stressors, health, affect, and memory failures. Participants reported anticipatory coping behaviors on one day with respect to 6 distinct stressor domains that could occur the following day. RESULTS: Multilevel models indicated that anticipatory coping changes from day to day and within stressor domains. Lagged associations suggested that yesterday's anticipatory coping for potential upcoming arguments is related to today's physical health and affect. Increased stagnant deliberation is associated with reduced cognitive reactivity (i.e., fewer memory failures) to arguments the next day. DISCUSSION: Taken together, these findings suggest that anticipatory coping is dynamic and associated with important daily outcomes.

Assessment of Adult Age differences in Task Engagement: The Utility of Systolic Blood Pressure.

The constructs of effort and engagement are central to many theoretical frameworks associated with the study of aging. Age differences in the effort associated with effortful cognitive operations have been hypothesized to account for aging effects in ability, and shifting goals and motivation have been hypothesized to be associated with differential levels of engagement across situations in younger and older adults. Unfortunately, the assessment of effort and engagement-constructs that we view as relatively synonymous-has suffered in the field of aging due to the lack of well-validated measures. We suggest that systolic blood pressure might provide an easy and valid means for examining age differences in mental effort, and present evidence in support of its usage. Existing findings clearly support its potential utility, but further empirical and theoretical work is necessary.

The impact of age and motivation on cognitive effort: implications for cognitive engagement in older adulthood.

We examined age differences in the effort required to perform the basic cognitive operations needed to achieve a specified objective outcome, and how hypothesized increases in effort requirements in later life are related to intrinsic motivation associated with enjoyment of and participation in effortful cognitive activities. Young (N = 59; 20-40 years) and older (N = 57; 64-85 years) adults performed a memory-search task varying in difficulty across trials, with systolic blood pressure responsivity-calculated as the increase over baseline during task performance-used as a measure of effort expenditure and task engagement. Consistent with expectations, older adults exhibited greater levels of responsivity (i.e., effort) at all levels of objective task difficulty, and this increase was reflected in subjective perceptions of difficulty. Older adults also exhibited greater levels of disengagement (i.e., effort withdrawal) than younger adults at higher levels of task difficulty, conceivably reflecting the disproportionately greater effort required for successful performance in the former group. We also found that, relative to younger adults, older adults' engagement was more sensitive to the importance attached to the task (i.e., motivation to do well). Finally, we also obtained evidence that increased costs associated with cognitive engagement in later life were negatively associated with intrinsic levels of motivation to engage in effortful cognitive activity. The results support the general conclusion that the costs of cognitive activity increase with age in adulthood, and that these costs influence individuals' willingness to engage resources in support of demanding cognitive activities.

Age and self-relevance effects on information search during decision making.

OBJECTIVES: We investigated how information search strategies used to support decision making were influenced by self-related implications of the task to the individual. Consistent with the notion of selective engagement, we hypothesized that increased self-relevance would result in more adaptive search behaviors and that this effect would be stronger in older adults than in younger adults. METHOD: We examined search behaviors in 79 younger and 81 older adults using a process-tracing procedure with 2 different decision tasks. The impact of motivation (i.e., self-related task implications) was examined by manipulating social accountability and the age-related relevance of the task. RESULTS: Although age differences in search strategies were not great, older adults were more likely than younger adults to use simpler strategies in contexts with minimal self-implications. Contrary to expectations, young and old alike were more likely to use noncompensatory than compensatory strategies, even when engaged in systematic search, with education being the most important determinant of search behavior. DISCUSSION: The results support the notion that older adults are adaptive decision makers and that factors other than age may be more important determinants of performance in situations where knowledge can be used to support performance.

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.

Age differences in the effort and costs associated with cognitive activity.

OBJECTIVES: We tested the hypothesis that aging is associated with an increase in the effort and costs associated with cognitive activity using systolic blood pressure (SBP) as a measure of effort. METHOD: Younger and older adults engaged in an initial task (Phase 1) for 5 min that was relatively low (adding single digits) or high (subtracting by 3 s) in cognitive demands. They then solved a series of multiplication problems for 3 min (Phase 2). Cardiovascular measures were collected throughout, and reactivity was examined as a function of age, initial task difficulty, and test phase. RESULTS: Older adults exhibited higher levels of reactivity than younger adults to cognitive engagement, with reactivity increasing with task difficulty. Difficulty of the initial task was also associated with greater effort and lower performance on the subsequent multiplication task, suggestive of fatigue or depletion. These fatigue effects were stronger for older adults. DISCUSSION: The results were consistent with expectations and provided support for the utility of SBP reactivity as a measure of cognitive effort in studies of aging.