Biomedical subjects

Rhoda Au

Publications and source records attributed to Rhoda Au.

17 recordsLinked to original sources

PubMed2026

A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.

Previously derived polygenic risk scores (PRSs) for Alzheimer's disease (AD) perform inconsistently across diverse ancestries. We developed an APOE-independent multiancestry AD PRS using genome-wide association study summary statistics applied to European ancestry, African American, Caribbean Hispanic and East Asian cohorts. PRS performance was evaluated in a large independent multiancestry dataset and validated in several additional multiancestry cohorts. The PRS was significantly associated with AD in European ancestry, African American, Caribbean Hispanic and Native American Hispanic groups with adjusted odds ratios between 1.14 and 1.52 per PRS standard deviation. PRS performance was validated in the replication cohorts (odds ratios: 1.21-1.65). The PRS was also associated with poorer memory, executive function and language performance, greater AD-related neuropathological burden, reduced hippocampal volume, lower cerebrospinal fluid amyloid-β42 and elevated total tau and phosphorylated tau, with stronger phosphorylated tau associations observed in women. Our findings support the value of ancestry-aware PRSs as a component of broader multimodal risk stratification frameworks.

Aged↗

PubMed2025

A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.

Alzheimer disease (AD) has a strong genetic basis, yet previously derived polygenic risk scores (PRS) are heavily weighted by the APOE locus and perform inconsistently across diverse ancestries. We developed an APOE-independent multi-ancestry AD PRS using genome-wide association study summary statistics from cohorts in the United States, Europe and East Asia that were applied to European ancestry (EA), African American (AA), Caribbean Hispanic (CH), and East Asian cohorts from the Alzheimer's Disease Genetics Consortium. PRS performance was evaluated in the multi-ancestry Alzheimer's Disease Sequencing Project (ADSP) dataset and validated in several additional multi-ancestry cohorts. The PRS was significantly associated with AD in the ADSP EA, AA, CH, and Native American Hispanic groups with adjusted odds ratios (ORs) between 1.14 and 1.52 per standard deviation of the PRS. PRS performance was validated in the replication cohorts (ORs 1.21-1.65). The PRS was also associated with poorer memory, executive function, and language performance; greater AD-related neuropathological burden (including CERAD, Braak stage, and Thal phase scores); reduced hippocampal volume; lower CSF Aβ42; and elevated total tau and phosphorylated tau (p-tau), with stronger p-tau associations observed in women. Longitudinal analyses revealed that individuals in the highest PRS decile exhibited the steepest cognitive decline, particularly among those who progressed to AD. Our findings demonstrate the utility of an ancestry-aware and APOE-independent PRS for advancing understanding of the genetic basis of AD across diverse populations. Associations observed with early biological and cognitive changes and potential sex-specific differences support the incorporation of a PRS in clinical trials and personalized intervention and prevention strategies.

Journal Article↗

PubMed2007

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

Blood Pressure↗

PubMed2006

The lifetime risk of stroke: estimates from the Framingham Study.

BACKGROUND AND PURPOSE: The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. METHODS: Framingham Original cohort participants (n=4897) who were stroke- and dementia-free at 55 years of age were followed biennially for up to 51 years (115 146 person years). We estimated the sex-specific 10-, 20-, and 30-year risks and LTR of developing a stroke by baseline age and blood pressure (BP) and compared it with the risk of developing Alzheimer disease (AD). RESULTS: A total of 875 participants (522 women) developed a first-ever stroke; 749 (448 women) had an ischemic stroke. LTR of stroke was high and remained similar at ages 55, 65, and 75 years, approximating 1 in 5 for women and 1 in 6 for men. Participants with a normal BP (<120/80 mm Hg) had approximately half the LTR of stroke compared with those with high BP (> or =140/90 mm Hg). The LTR of AD at age 65 (292 participants; 211 women) approximated 1 in 5 for women and 1 in 10 for men. The LTR of developing either stroke or dementia approximated 1 in 3 in both sexes. CONCLUSIONS: The LTR of stroke in middle-aged adults is 1 in 6 or more, which is equal to or greater than the LTR of AD. Women had a higher risk because of longer life expectancy. BP is a significant determinant of the LTR of stroke, and promotion of normal BP levels in the community might be expected to substantially reduce this risk.

Age Factors↗

PubMed2006

Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study.

BACKGROUND: Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. OBJECTIVE: To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. DESIGN, SETTING, AND PARTICIPANTS: A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. MAIN OUTCOME MEASURES: Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels. RESULTS: Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the follow-up. After adjustment for age, sex, apolipoprotein E epsilon4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all-cause dementia (95% confidence interval, 0.29-0.97; P=.04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P=.14). Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P<.001) in a subset of 488 participants. We found no other significant associations. CONCLUSION: The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study.

Aged↗

PubMed2006

Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study.

BACKGROUND: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. OBJECTIVE: To compare the risk of developing AD in subjects with and without DM. DESIGN: Prospective community-based cohort study. PARTICIPANTS: Framingham Study Original cohort participants who were dementia free and attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). MAIN OUTCOME MEASURES: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose >or=200 mg/dL [>or=11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. RESULTS: At baseline, 202 participants (9.1%) had DM. During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E epsilon4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). CONCLUSION: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors.

Aged↗

PubMed2006

Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study.

OBJECTIVE: To examine the relationship between white matter hyperintensity (WMH) volume on magnetic resonance images and cognitive tests in a large, population-based sample. METHODS: Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort. The WMH volume relative to total cranial volume was computed; WMH volumes more than 1 SD above the age-predicted mean were defined as large. Adjusting for age, sex, education, height, and Framingham Stroke Risk Profile, we examined the relationship between WMH and 3 cognitive factors derived from a neuropsychological test battery (verbal memory, visuospatial memory and organization, and visual scanning and motor speed) and 3 individual measures of new learning, abstract reasoning, and naming. RESULTS: Compared with those with no or little WMH volume, participants with large WMH volume performed worse on the cognitive factors of visuospatial memory and organization (P = .04) and visual scanning and motor speed (P = .01), as well as on new learning (P = .04), but not on verbal memory (P = .52). CONCLUSIONS: In this younger community-based population of nondemented individuals, those with large WMH volume, as compared with those with less or no WMH volumes, performed significantly worse in cognitive domains generally associated with frontal lobe systems and, to a lesser extent, the medial temporal area. Further study will clarify whether large WMH volume and associated cognitive impairment lead to future risk of stroke or dementia.

Age Factors↗

PubMed2006

Visual association pathology in preclinical Alzheimer disease.

The transition from normal aging to mild cognitive impairment to Alzheimer disease (AD) is often indistinct. Imaging studies suggest early changes in posterior brain regions, including posterior temporoparietal and occipital cortex, but pathologic studies show initial changes in the medial temporal lobe with progressive neocortical involvement as cognition deteriorates. We evaluated the regional distribution of AD pathology in 41 elderly brain donors from the Framingham Heart Study who were cognitively intact, mildly impaired, or demented on the basis of probable AD. We found that 52% of the cognitively intact subjects, and all subjects with mild cognitive impairment or dementia, had dense neurofibrillary tangles (NFTs), neuropil threads, and tau-immunoreactive neurites surrounding neuritic plaques (NPs) in visual association cortex Brodmann area 19. All cognitively intact subjects with area 19 NFTs also had dense core NP and beta amyloid (Abeta) angiopathy in area 19. Area 19 pathology was occasionally present in the absence of substantial pathology in the hippocampus or entorhinal cortex and was not correlated with medial temporal lobe pathology. Dense AD pathology in area 19 is present in some cognitively intact subjects with preclinical AD. The unique metabolic, connectional, and vascular features of this region may confer enhanced vulnerability to neurodegeneration.

Aged↗

PubMed2005

Genome-wide scan for white matter hyperintensity: the Framingham Heart Study.

BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. METHODS: Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16+/-12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098+/-0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. RESULTS: A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. CONCLUSIONS: We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

Adult↗

PubMed2005

Homocysteine and cognitive performance in the Framingham offspring study: age is important.

Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

Adult↗

PubMed2005

Bone mineral density and the risk of Alzheimer disease.

BACKGROUND: Some, but not all, studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women. Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration. OBJECTIVE: To examine whether low BMD in elderly individuals is associated with an increased risk of developing Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 987 subjects (610 women) who were cognitively intact and had baseline BMD measured at the femoral neck, the trochanter, and the radial shaft between 1988 and 1989. MAIN OUTCOME MEASURES: Incidence of AD and all-cause dementia during an 8-year follow-up period. RESULTS: Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04; 95% confidence interval, 1.11-3.75) and all-cause dementia (hazard ratio, 2.01; 95% confidence interval, 1.16-3.49) compared with those in higher quartiles after adjusting for age, sex, apolipoprotein E epsilon4, baseline homocysteine level, education, estrogen use, smoking, and stroke. A similar but statistically nonsignificant relationship was observed between BMD of the femoral trochanter and AD, while no such relationship was seen between radial BMD and AD or all-cause dementia. In men, there was a trend toward an inverse relationship between BMD and the risk of AD, but the relationship was not statistically significant at any of the 3 sites. CONCLUSIONS: Low femoral neck BMD was associated with approximately 2 times the risk of AD and all-cause dementia in women but not men, suggesting the possibility that cumulative estrogen exposure may influence the risk of developing AD. Additional studies are needed to confirm this correlation.

Aged↗

PubMed2005

Measures of brain morphology and infarction in the framingham heart study: establishing what is normal.

Numerous anatomical and brain imaging studies find substantial differences in brain structure between men and women across the span of human aging. The ability to extend the results of many of these studies to the general population is limited, however, due to the generally small sample size and restrictive health criteria of these studies. Moreover, little attention has been paid to the possible impact of brain infarction on age-related differences in regional brain volumes. Given the current lack of normative data on gender and aging related differences in regional brain morphology, particularly with regard to the impact of brain infarctions, we chose to quantify brain MRIs from more than 2200 male and female participants of the Framingham Heart Study who ranged in age from 34 to 97 years. We believe that MRI analysis of the Framingham Heart Study more closely represents the general population enabling more accurate estimates of regional brain changes that occur as the consequence of normal aging. As predicted, men had significantly larger brain volumes than women, but these differences were generally not significant after correcting for gender related differences in head size. Age explained approximately 50% of total cerebral brain volume differences, but age-related differences were generally small prior to age 50, declining substantially thereafter. Frontal lobe volumes showed the greatest decline with age (approximately 12%), whereas smaller differences were found for the temporal lobes (approximately 9%). Age-related differences in occipital and parietal lobe were modest. Age-related gender differences were generally small, except for the frontal lobe where men had significantly smaller lobar brain volumes throughout the age range studied. The prevalence of MRI infarction was common after age 50, increased linearly with age and was associated with significantly larger white matter hyperintensity (WMH) volumes beyond that associated with age-related differences in these measures. Amongst men, the presence of MRI infarction was associated with significant age-related reductions in total brain volume. Finally, statistically significant associations were found between the volume of MRI infarcts in cubic centimeters and all brain measures with the exception of parietal lobe volume for individuals where the volume of MRI infarctions was measured. These data serve to define age and gender differences in brain morphology for the Framingham Heart Study. To the degree participants of the Framingham Heart Study are representative the general population, these data can serve as norms for comparison with morphological brain changes associated with aging and disease. In this regard, these cross-sectional quantitative estimates suggest that age-related tissue loss differs quantitatively and qualitatively across brain regions with only minor differences between men and women. In addition, MRI evidence of cerebrovascular disease is common to the aging process and associated with smaller regional brain volumes for a given age, particularly for men. We believe quantitative MRI studies of the Framingham community enables exploration of numerous issues ranging from understanding normal neurobiology of brain aging to assessing the impact of various health factors, particularly those related to cerebrovascular disease, that appear important to maintaining brain health for the general population.

Adult↗

PubMed2004

Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are areas of low signal intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI) corresponding to hemosiderin deposits in the perivascular space. Microangiopathy from atherosclerosis or amyloid angiopathy might lead to the formation of these lesions; therefore, there may be associations between CMBs and cardiovascular risk factors, APOE allele status, and brain morphology. We examined these relationships in the Framingham Study (FHS). METHODS: In 472 subjects from the FHS Offspring and Cohort, we related CMB status to age, sex, systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, smoking, diabetes, total hemispheric brain volume, white matter hyperintensity volume (WMHV), and APOE allele status. RESULTS: Overall prevalence of CMBs was 4.7%, but CMBs were more prevalent with advanced age and male sex. Blood pressure, brain volume, and WMHV were related to CMBs in crude analysis but not after adjustment for age and sex. There were no significant relationships demonstrated between CMBs and APOE allele status, cholesterol, smoking, or diabetes. CONCLUSIONS: There is a low prevalence of CMBs in the community and a strong relationship with increasing age and male sex. We found no independent relationships with cardiovascular risk factors, APOE status, brain volumes, or WMH.

Age Factors↗

PubMed2004

Dementia after stroke: the Framingham Study.

BACKGROUND AND PURPOSE: Identification of risk factors for dementia after stroke is best performed in comparison with stroke-free controls, because older subjects at high risk for stroke also have a substantial risk of dementia in the absence of stroke. Previous case-control studies were hospital-based. We used a nested case-control design to prospectively evaluate these risk factors in the community-based Framingham Study cohort. METHODS: We compared 212 subjects who were free of dementia in January 1982 and sustained a first stroke after this date, with 1060 age- and sex-matched, stroke- and dementia-free controls. We calculated 10-year risks of dementia (by Diagnostic and Statistical Manual of Mental Disorders, Volume IV criteria) developing in cases and controls and also estimated the hazard ratios within subgroups defined by exposure to various demographic factors (age, gender, education), stroke-related features (right or left hemisphere, stroke type, second stroke), stroke risk factors (hypertension, diabetes, atrial fibrillation, smoking) and apolipoprotein E genotype. RESULTS: Dementia developed in 19.3% of cases and 11.0% of controls. Baseline stroke doubled the risk of dementia (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.5 to 3.1) and adjustment for age, sex, education, and exposure to individual stroke risk factors did not diminish the risk (HR: 2.4; 95% CI: 1.6 to 3.7). The HR was higher in younger subjects (age younger than 80 years [HR: 2.6; 95% CI: 1.5 to 4.5]), apolipoprotein E 3/3 homozygotes (HR: 3.4; 95% CI: 2.0 to 5.8), and high school graduates (HR: 2.4; 95% CI: 1.5 to 3.9). CONCLUSIONS: Stroke increases a subject's risk of dementia as compared with age- and sex-matched controls. Primary and secondary prevention of stroke should significantly decrease the risk of all dementia.

Aged↗

PubMed2004

Managing and analysing data from a large-scale study on Framingham Offspring relating brain structure to cognitive function.

At the Framingham Heart Study under separate research grant funding from the National Institute of Aging, NIH, we are gathering brain structure and cognitive information on the Framingham Offspring, creating one of the largest known data sets to assess changes in brain structure associated with normative ageing and cognitive decline. Subject recruitment, data collection, data management and statistical analysis require a collaborative integrated effort on the part of the Framingham project team. Here we describe this effort, as well as the various brain structure and cognitive function parameters we are now collecting. We are currently performing analyses of data collected through 2002, and we discuss the statistical issues arising relating brain structure parameters to cognitive function.

Aged↗

PubMed2004

Framingham stroke risk profile and lowered cognitive performance.

BACKGROUND AND PURPOSE: The primary objective of this work was to describe the relationships between 10-year risk for stroke and multiple measures of cognitive performance for a large community-based sample of individuals who were free of clinical stroke and dementia at the time of risk assessment. METHODS: Participants were 1011 men and 1164 women from the Framingham Offspring Study. The Framingham Stroke Risk Profile was used to assess 10-year risk of stroke. Using a cross-sectional design, we assessed 10-year risk of stroke, the predictor variable, and cognitive performance, the outcome variable, at examination 7 of the Framingham Offspring Study. Multivariable linear regression models were used to relate 10-year risk of stroke to cognitive tests measuring multiple domains of cognitive functioning. RESULTS: With statistical adjustment for age, education, sex, and other correlates of both stroke and cognitive ability, an inverse association between increments in 10-year risk of stroke and cognitive performance level was observed for tests indexing visual-spatial memory, attention, organization, scanning, and abstract reasoning. CONCLUSIONS: In stroke- and dementia-free individuals, higher 10-year risk for stroke is associated with performance decrements in multiple cognitive domains.

Adult↗

PubMedDate not supplied

New norms for a new generation: cognitive performance in the framingham offspring cohort.

A previous publication presented normative data on neuropsychological tests stratified by age, gender, and education based on the Original Cohort of the Framingham Heart Study. Many contemporary investigations include subject samples with higher levels of education, a factor known to affect cognitive performance. Secular change in education prompted the reexamination of norms in the children of the Original Cohort. The study population consisted of 853 men and 988 women from the Offspring Study, free of clinical neurological disease, who underwent a neuropsychological examination, which included tests given to their parents in 1974 to 1976 as well as additional newer tests to provide a more comprehensive battery. The Offspring population overall was more evenly distributed by gender and better educated. Their performance on cognitive tests was superior to that of the Original Cohort. Multivariable analyses revealed that more years of education explained only a part of the cohort differences. These findings suggest that continued surveillance of each generation is necessary to document the impact that unique social and economic variables have on cognitive function. Here, the authors provide updated normative data.

Adult Children↗