The Observational Scale of Level of Arousal: A brief tool for assessing and monitoring level of arousal in patients with delirium outside the ICU.

OBJECTIVES: Altered level of arousal, encompassing drowsiness and hypervigilance, affects at least 10% of acutely unwell patients. Existing scales provide limited coverage of milder changes in level of arousal. We devised the Observational Scale of Level of Arousal (OSLA) to enable more detailed arousal assessment. Here, we provide a preliminary case-control study of performance of the OSLA in assessing abnormal level of arousal associated with delirium outside the ICU. METHODS: Hip fracture patients (N = 108, median age = 82 years) were assessed for delirium pre- and post-operatively using the Confusion Assessment Method and the Delirium Rating Scale-Revised-98. The OSLA has four graded items assessing eye opening, eye contact, posture, and movement (score range 0 [normal arousal]-15). We assessed the psychometric and diagnostic characteristics of the OSLA. Adjusted linear mixed effects models were used to explore responsiveness of the OSLA to within-patient change in delirium status. RESULTS: A total of 44 patients (40.7%) were diagnosed with delirium. OSLA scores were higher in delirium (pooled median = 3, InterQuartile Range [IQR] = 2-5) compared to no delirium (pooled median = 1, IQR = 1-2; P-values <.05 to <.001). The Area under the Receiver Operating Characteristic curve was 0.82 (95% Confidence Interval (CI) = 0.77-0.86). OSLA scores were responsive to change in delirium status (ß = -3.09. SE = 1.41, P < .03). CONCLUSIONS: This study provides preliminary evidence supporting use of the OSLA as an instrument for identifying abnormal level of arousal associated with delirium and monitoring this longitudinally. Further validation in larger cohorts with blinded raters is required. J Am Geriatr Soc 68:-, 2020.

Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study.

Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936 (n = 603); and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study (n = 155). Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32-0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease.

Sleep and cognitive aging in the eighth decade of life.

We examined associations between self-reported sleep measures and cognitive level and change (age 70-76 years) in a longitudinal, same-year-of-birth cohort study (baseline N = 1091; longitudinal N = 664). We also leveraged GWAS summary data to ascertain whether polygenic scores (PGS) of chronotype and sleep duration related to self-reported sleep, and to cognitive level and change. Shorter sleep latency was associated with significantly higher levels of visuospatial ability, processing speed, and verbal memory (ß ≥ |0.184|, SE ≤ 0.075, p ≤ 0.003). Longer daytime sleep duration was significantly associated slower processing speed (ß = -0.085, SE = 0.027, p = 0.001), and with steeper 6-year decline in visuospatial reasoning (ß = -0.009, SE = 0.003, p = 0.008), and processing speed (ß = -0.009, SE = 0.002, p < 0.001). Only longitudinal associations between longer daytime sleeping and steeper cognitive declines survived correction for important health covariates and false discovery rate (FDR). PGS of chronotype and sleep duration were nominally associated with specific self-reported sleep characteristics for most SNP thresholds (standardized ß range = |0.123 to 0.082|, p range = 0.003 to 0.046), but neither PGS predicted cognitive level or change following FDR. Daytime sleep duration is a potentially important correlate of cognitive decline in visuospatial reasoning and processing speed in older age, whereas cross-sectional associations are partially confounded by important health factors. A genetic propensity toward morningness and sleep duration were weakly, but consistently, related to self-reported sleep characteristics, and did not relate to cognitive level or change.

Development and feasibility of a smartphone-based test for the objective detection and monitoring of attention impairments in delirium in the ICU.

PURPOSE: Delirium in the ICU is under-diagnosed. We evaluated feasibility and performance of a novel smartphone-based test for objectively detecting inattention in delirium. MATERIAL AND METHODS: DelApp-ICU combines a behavioural assessment and an attention task, whereby participants follow simple commands and count serially presented circles (score range 0-12, lower scores indicating worse performance). We assessed feasibility through staff interviews. Then we performed a preliminary case-control study in patients with and without delirium (ascertained with the Confusion Assessment Method for the ICU) who underwent the DelApp-ICU on up to 4 days. RESULTS: Forty-six patients (median age = 57.5 years, range 18-83) were assessed 89 times in total (N's = 46, 29, 10 and 4 for subsequent assessments; 33.7% delirious). DelApp-ICU scores were lower in delirium (N = 20; median = 0.5, Inter-Quartile Range (IQR) = 0-4.75) compared to no delirium (N = 26, median = 12, IQR = 8-12) on days 1, 2 and 3 (p < 0.001, p < 0.001 and p < 0.05, respectively). A DelApp-ICU score ≤6 was 100% sensitive and 96% specific to delirium on day 1. Positive and Negative Predictive Values were 91% and 100%, respectively. DelApp-ICU scores were responsive to changes in CAM-ICU status. CONCLUSIONS: DelApp-ICU shows promise for assessing inattention and delirium in ICU patients, including longitudinally monitoring deficits and providing a metric of delirium severity.

Physical fitness and dementia risk in the very old: a study of the Lothian Birth Cohort 1921.

BACKGROUND: Previous studies have demonstrated that individual measures of fitness - such as reduced pulmonary function, slow walking speed and weak handgrip - are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old. METHODS: Subjects (n = 488) were enrolled in the Lothian Birth Cohort 1921 and aged 79 at baseline. Dementia cases arising after enrolment were determined using data from death certificates, electronic patient records and clinical reviews. Fitness measures included grip strength, forced expiratory volume in 1 s (FEV1) and walking speed over 6 m, measured at 79 years. Dementia risk associated with each fitness variable was initially determined by logistic regression analysis, followed by Cox regression analysis, where death was considered as a competing risk. APOE ε4 status, age, sex, height, childhood IQ, smoking, history of cardiovascular or cerebrovascular disease, hypertension and diabetes were included as additional variables. Cumulative incidence graphs were calculated using Aalen-Johansen Estimator. RESULTS: Although initial results indicated that greater FEV1 was associated with an increased risk of dementia (OR (odds ratio per unit increase) 1.93, p = 0.03, n = 416), taking into account the competing risk of mortality, none of the fitness measures were found to be associated with dementia; FEV1 (HR (hazard ratio per unit increase) 1.30, p = 0.37, n = 416), grip strength (HR 0.98, p = 0.35, n = 416), walking speed (HR 0.99, p = 0.90, n = 416). The presence of an APOE ɛ4 allele was however an important predictor for dementia (HR 2.85, p < 0.001, n = 416). Cumulative incidence graphs supported these findings, with an increased risk of dementia for APOE ɛ4 carriers compared with non-carriers. While increased FEV1 was associated with reduced risk of death, there was no reduction in risk for dementia. CONCLUSIONS: In contrast to previous studies, this study found that lower fitness beyond age 79 was not a risk factor for subsequent dementia. This finding is not explained by those with poorer physical fitness, who would have been more likely to develop dementia, having died before onset of dementia symptoms.

Longitudinal serum S100ß and brain aging in the Lothian Birth Cohort 1936.

Elevated serum and cerebrospinal fluid concentrations of S100ß, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100ß concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100ß and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume. Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100ß was cross-sectionally associated with poorer general fractional anisotropy (r = -0.150, p = 0.001), which was strongest in the anterior thalamic (r = -0.155, p < 0.001) and cingulum bundles (r = -0.111, p = 0.005), and survived false discovery rate correction. Longitudinally, there were no significant associations between changes in brain imaging parameters and S100ß after false discovery rate correction. These data provide some weak evidence that S100ß may be an informative biomarker of brain white matter aging.

A Novel Computerized Test for Detecting and Monitoring Visual Attentional Deficits and Delirium in the ICU.

OBJECTIVES: Delirium in the ICU is associated with poor outcomes but is under-detected. Here we evaluated performance of a novel, graded test for objectively detecting inattention in delirium, implemented on a custom-built computerized device (Edinburgh Delirium Test Box-ICU). DESIGN: A pilot study was conducted, followed by a prospective case-control study. SETTING: Royal Infirmary of Edinburgh General ICU. PATIENTS: A pilot study was conducted in an opportunistic sample of 20 patients. This was followed by a validation study in 30 selected patients with and without delirium (median age, 63 yr; range, 23-84) who were assessed with the Edinburgh Delirium Test Box-ICU on up to 5 separate days. Presence of delirium was assessed using the Confusion Assessment Method for the ICU. MEASUREMENTS AND MAIN RESULTS: The Edinburgh Delirium Test Box-ICU involves a behavioral assessment and a computerized test of attention, requiring patients to count slowly presented lights. Thirty patients were assessed a total of 79 times (n = 31, 23, 15, 8, and 2 for subsequent assessments; 38% delirious). Edinburgh Delirium Test Box-ICU scores (range, 0-11) were lower for patients with delirium than those without at the first (median, 0 vs 9.5), second (median, 3.5 vs 9), and third (median, 0 vs 10.5) assessments (all p < 0.001). An Edinburgh Delirium Test Box-ICU score less than or equal to 5 was 100% sensitive and 92% specific to delirium across assessments. Longitudinally, participants' Edinburgh Delirium Test Box-ICU performance was associated with delirium status. CONCLUSIONS: These findings suggest that the Edinburgh Delirium Test Box-ICU has diagnostic utility in detecting ICU delirium in patients with Richmond Agitation and Sedation Scale Score greater than -3. The Edinburgh Delirium Test Box-ICU has potential additional value in longitudinally tracking attentional deficits because it provides a range of scores and is sensitive to change.

Correction: Cognitive Test Scores in UK Biobank: Data Reduction in 480,416 Participants and Longitudinal Stability in 20,346 Participants.

[This corrects the article DOI: 10.1371/journal.pone.0154222.].

Cognitive Test Scores in UK Biobank: Data Reduction in 480,416 Participants and Longitudinal Stability in 20,346 Participants.

UK Biobank includes 502,649 middle- and older-aged adults from the general population who have undergone detailed phenotypic assessment. The majority of participants completed tests of cognitive functioning, and on average four years later a sub-group of N = 20,346 participants repeated most of the assessment. These measures will be used in a range of future studies of health outcomes in this cohort. The format and content of the cognitive tasks were partly novel. The aim of the present study was to validate and characterize the cognitive data: to describe the inter-correlational structure of the cognitive variables at baseline assessment, and the degree of stability in scores across longitudinal assessment. Baseline cognitive data were used to examine the inter-correlational/factor-structure, using principal components analysis (PCA). We also assessed the degree of stability in cognitive scores in the subsample of participants with repeat data. The different tests of cognitive ability showed significant raw inter-correlations in the expected directions. PCA suggested a one-factor solution (eigenvalue = 1.60), which accounted for around 40% of the variance. Scores showed varying levels of stability across time-points (intraclass correlation range = 0.16 to 0.65). UK Biobank cognitive data has the potential to be a significant resource for researchers looking to investigate predictors and modifiers of cognitive abilities and associated health outcomes in the general population.

Brain iron deposits and lifespan cognitive ability.

Several studies have reported associations between brain iron deposits and cognitive status, and cardiovascular and neurodegenerative diseases in older individuals, but the mechanisms underlying these associations remain unclear. We explored the associations between regional brain iron deposits and different factors of cognitive ability (fluid intelligence, speed and memory) in a large sample (n = 662) of individuals with a mean age of 73 years. Brain iron deposits in the corpus striatum were extracted automatically. Iron deposits in other parts of the brain (i.e., white matter, thalamus, brainstem and cortex), brain tissue volume and white matter hyperintensities (WMH) were assessed separately and semi-automatically. Overall, 72.8 % of the sample had iron deposits. The total volume of iron deposits had a small but significant negative association with all three cognitive ability factors in later life (mean r = -0.165), but no relation to intelligence in childhood (r = 0.043, p = 0.282). Regression models showed that these iron deposit associations were still present after control for a variety of vascular health factors, and were separable from the association of WMH with cognitive ability. Iron deposits were also associated with cognition across the lifespan, indicating that they are relevant for cognitive ability only at older ages. Iron deposits might be an indicator of small vessel disease that affects the neuronal networks underlying higher cognitive functioning.

Compensation or inhibitory failure? Testing hypotheses of age-related right frontal lobe involvement in verbal memory ability using structural and diffusion MRI.

Functional neuroimaging studies report increased right prefrontal cortex (PFC) involvement during verbal memory tasks amongst low-scoring older individuals, compared to younger controls and their higher-scoring contemporaries. Some propose that this reflects inefficient use of neural resources through failure of the left PFC to inhibit non-task-related right PFC activity, via the anterior corpus callosum (CC). For others, it indicates partial compensation - that is, the right PFC cannot completely supplement the failing neural network, but contributes positively to performance. We propose that combining structural and diffusion brain MRI can be used to test predictions from these theories which have arisen from fMRI studies. We test these hypotheses in immediate and delayed verbal memory ability amongst 90 healthy older adults of mean age 73 years. Right hippocampus and left dorsolateral prefrontal cortex (DLPFC) volumes, and fractional anisotropy (FA) in the splenium made unique contributions to verbal memory ability in the whole group. There was no significant effect of anterior callosal white matter integrity on performance. Rather, segmented linear regression indicated that right DLPFC volume was a significantly stronger positive predictor of verbal memory for lower-scorers than higher-scorers, supporting a compensatory explanation for the differential involvement of the right frontal lobe in verbal memory tasks in older age.

Sedentary behavior in the first year after stroke: a longitudinal cohort study with objective measures.

OBJECTIVE: To quantify longitudinal changes in sedentary behavior (ie, nonexercise seated or lying behavior) after stroke to ascertain whether reducing sedentary behavior might be a new therapeutic target. DESIGN: Longitudinal cohort study of patients with acute stroke who were followed over 1 year. SETTING: Acute teaching hospital or outpatient clinic, and the community after discharge. PARTICIPANTS: A convenience sample of patients with acute stroke (N=96; median age, 72y, interquartile range [IQR]=64-80y; 67% men; median National Institute of Health Stroke Scale score=2, IQR=1-3) who were assessed at 1, 6, and 12 months after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Objective measures of amount and pattern of time spent in sedentary behavior: total sedentary time, weighted median sedentary bout length, and fragmentation index. RESULTS: Stroke survivors were highly sedentary, spending on average 81% of the time per day in sedentary behavior: median=19.9 hours (IQR=18.4-22.1h), 19.1 hours (17.8-20.8h), and 19.3 hours (17.3-20.9h) at 1, 6, and 12 months, respectively. Longitudinal changes in sedentary behavior were estimated using linear mixed effects models. Covariates were age, sex, stroke severity (National Institute of Health Stroke Scale score), physical capacity (6-minute walk distance), and functional independence (Nottingham Extended Activities of Daily Living Questionnaire score). Higher stroke severity and less functional independence were associated cross-sectionally with more sedentary behavior (ß=.11, SE=.05, P=.020 and ß=-.11, SE=.01, P<.001, respectively). Importantly, the pattern of sedentary behavior did not change over the first year after stroke and was independent of functional ability. CONCLUSIONS: Stroke survivors were highly sedentary and remained so a year after stroke independently of their functional ability. Developing interventions to reduce sedentary behavior might be a potential new therapeutic target in stroke rehabilitation.

The dynamic relationship between cognitive function and positive well-being in older people: a prospective study using the English Longitudinal Study of Aging.

There is evidence that having a stronger sense of positive well-being may be a potential resource for healthier aging as represented by slower physical decline, reduced risk of frailty and longer survival. However, it is unclear whether positive well-being is protective of another crucial component of healthy aging, cognitive function, or whether it has a bidirectional relationship with cognitive function. We use multilevel models with within-person centering to estimate the within- and between-person association between cognitive function and positive well-being in 4 waves of data from the English Longitudinal Study of Ageing (ELSA), (N = 10985, aged 50-90 years at wave 1). Our findings show that, although most variation in cognitive function was explained by age, and most variation in well-being was explained by depression, small but significant associations between cognition and well-being remained after variation in age and depression were controlled. In models where cognition was the outcome, the association was mainly because of variation in mean levels of well-being between persons. In models where well-being was the outcome, the association was mainly because of within-person fluctuation in cognitive test performance. Exercise and depression were the most important moderating influences on the association between cognition and positive well-being. Depression had greater effect upon this association for those with higher well-being, but exercise protected cognitive performance against the adverse effects of lower well-being.

Life course influences of physical and cognitive function and personality on attitudes to aging in the Lothian Birth Cohort 1936.

ABSTRACT Background: Reports of attitudes to aging from older people themselves are scarce. Which life course factors predict differences in these attitudes is unknown. Methods: We investigated life course influences on attitudes to aging in healthy, community-dwelling people in the UK. Participants in the Lothian Birth Cohort 1936 completed a self-report questionnaire (Attitudes to Aging Questionnaire, AAQ) at around age 75 (n = 792, 51.4% male). Demographic, social, physical, cognitive, and personality/mood predictors were assessed, around age 70. Cognitive ability data were available at age 11. Results: Generally positive attitudes were reported in all three domains: low Psychosocial Loss, high Physical Change, and high Psychological Growth. Hierarchical multiple regression found that demographic, cognitive, and physical variables each explained a relatively small proportion of the variance in attitudes to aging, with the addition of personality/mood variables contributing most significantly. Predictors of attitudes to Psychosocial Loss were high neuroticism; low extraversion, openness, agreeableness, and conscientiousness; high anxiety and depression; and more physical disability. Predictors of attitudes to Physical Change were: high extraversion, openness, agreeableness, and conscientiousness; female sex; social class; and less physical disability. Personality predictors of attitudes to Psychological Growth were similar. In contrast, less affluent environment, living alone, lower vocabulary scores, and slower walking speed predicted more positive attitudes in this domain. Conclusions: Older people's attitudes to aging are generally positive. The main predictors of attitude are personality traits. Influencing social circumstances, physical well-being, or mood may result in more positive attitudes. Alternatively, interventions to influence attitudes may have a positive impact on associated physical and affective changes.

Selective white matter pathology induces a specific impairment in spatial working memory.

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice.

Assessing dual-task performance using a paper-and-pencil test: normative data.

Although several studies have described dual-tasking ability in normal aging, Mild Cognitive Impairment and Alzheimer's disease, no normative data for dual-task performance exist. Dual-tasking ability of 436 healthy individuals, aged 16-88 years, was assessed using a new paper-and-pencil dual-task paradigm. In this study, no age effect was detected, providing strong evidence that age does not affect dual-tasking abilities. Psychometric data for this new assessment are presented, which may enable clinicians and researchers to use this paradigm as a means of examining attentional control in dual-tasking.

Network generation enhances interpretation of proteomic data from induced apoptosis.

Thirteen proteins (identified with 2-D gels and MALDI-TOF MS) are significantly altered during staurosporine-induced apoptosis in SH-SY5Y cells. To gain further insight into the integrated cellular response to apoptosis, we have investigated whether a network can be generated of direct and indirect interactions between these 13 proteins. A network that contains 12 out of the 13 proteins was generated using Ingenuity Pathway Analysis (IPA) and this network is dominated (89%) by direct protein-protein interactions. This network scored 34 with IPA. Bootstrapping 1000 random lists of 13 proteins suggested that the frequency of this score occurring by chance was 1 in 500. We examined whether subsets of proteins such as HSPs, which were elevated after staurosporine, had a disproportionate impact on the network generated. There was no evidence that any subset of 8 from the 13 proteins contributed disproportionately to the network. Network generation, using IPA, identified common features (such as endoplasmic reticular stress protein interactions) in apoptotic studies from different laboratories. The generation of protein interaction networks clearly enhances the interpretation of proteomic data, but only when interpreted cautiously, particularly in respect of statistical analyses.

Age-related changes in memory and fluid reasoning in a sample of healthy old people.

UNLABELLED: Participants in the Healthy Old People in Edinburgh (HOPE) study (N = 398) were assessed on Raven's Progressive Matrices and Logical Memory on up to three occasions. Covariates included education, social class, disease and medication status, blood pressure and study outcome. Raven's score declined linearly with age, whereas decline in Logical Memory was accelerating. There was significant variation in individuals' rates of decline for Ravens but not Logical Memory. Slope-intercept covariances were not significant. Those who later developed dementia already exhibited lower scores, more so for Logical Memory than Raven's. Death and study attrition were related to performance, again greater for Logical Memory. CONCLUSIONS: The HOPE approach of progressive screening is a feasible and practical method for studying healthy cognitive ageing. As predicted for an initially healthy sample, rates of decline were relatively homogeneous. The hypothesis of differential decline was not supported, nor was a strict interpretation of the hypothesis that cognitive ageing is entirely pathology driven.

Cognitive ability at age 11 and 70 years, information processing speed, and APOE variation: the Lothian Birth Cohort 1936 study.

The e4 allele of the apolipoprotein E (APOE) gene confers risk of Alzheimer's disease and, in some studies, relates to cognitive ability and decline in older people without Alzheimer's disease. Its relationship with processing speed, a contributor to cognitive decline with age, is largely unknown. This study tests the association of APOE with cognition and speed, with and without covarying childhood mental ability. The 1,013 participants were tested on cognitive ability at age 11 as part of the Scottish Mental Survey of 1947 and, at age 70, were tested on reasoning, working memory, information processing speed, and executive function. The results showed that APOE was associated with the general cognitive factor, 2 nonverbal tests, and choice reaction time (RT) variability; as expected, the e4 allele was the risk allele. RT measures and a general speed factor were nonlinearly related to APOE when factoring childhood ability (p < .05): The correlation between childhood ability and speed was lower in e4 allele carriers. APOE has an influence on nonverbal cognition in old age and interacts with childhood IQ to influence processing speed.