Rate Of Cognitive Change Research Articles

The effect of vascular risk factors on the rate of cognitive change in older adults: Data from the Australian Imaging Biomarkers and Lifestyle (AIBL) flagship study

The effect of vascular risk factors on the rate of cognitive change in older adults: Data from the Australian Imaging Biomarkers and Lifestyle (AIBL) flagship study

BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimer's disease (AD)–related cognitive impairment. We aimed to determine the relationship between BDNF Val66Met and beta-amyloid (Aβ) on cognitive decline, hippocampal atrophy, and Aβ accumulation over 36 months in 165 healthy adults enrolled in the Australian Imaging, Biomarkers and Lifestyle study. In healthy adults with high Aβ, Met carriers showed significant and moderate-to-large declines in episodic memory, executive function, and language, and greater hippocampal atrophy over 36 months, compared with Val/Val homozygotes. BDNF Val66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low Aβ. BDNF Val66Met did not relate to the amount of Aβ or to the rate of Aβ accumulation in either group. High Aβ levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.

Rapid Decline in Episodic Memory in Healthy Older Adults with High Amyloid-β

High levels of amyloid-β (Aβ) have been associated with greater rates of decline in episodic memory over 18 months in healthy older adults. Serial assessments over shorter time intervals may facilitate earlier detection of Aβ-related memory decline in healthy older adults. In forty-four healthy older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Rate of Change Sub-Study, we compared rates of change in cognition over six months in healthy older adults with high and low levels of Aβ. High Aβ was associated with greater decline in episodic memory measures over 6 months in healthy older adults.

Relation of neuropathology with cognitive decline among older persons without dementia

Objective: Although it is now widely accepted that dementia has a long preclinical phase during which neuropathology accumulates and cognition declines, little is known about the relation of neuropathology with the longitudinal rate of change in cognition among older persons without dementia. We quantified the burden of the neuropathologies of the three most common causes of dementia [i.e., Alzheimer’s disease (AD), cerebrovascular disease (CVD), and Lewy body disease (LBD)] and examined their relation with cognitive decline in a large cohort of persons without dementia proximate to death.Methods: A total of 467 deceased participants without dementia from two longitudinal clinical-pathologic studies, Rush Memory and Aging Project and Religious Orders Study, completed a mean of 7 annual evaluations including 17 cognitive tests. Neuropathologic examinations provided quantitative measures of AD (i.e., amyloid load, tangle density), CVD (i.e., macroscopic infarcts, microinfarcts), and neocortical Lewy bodies. Random coefficient models were used to examine the relation of the neuropathologies with rates of global cognitive decline as well as decline in four specific cognitive systems.Results: At autopsy, 82% of persons without dementia had amyloid, 100% had tangles, 29% had macroscopic infarcts, 25% had microinfarcts, and 6% had neocortical Lewy bodies. Global cognition declined a mean of 0.034 unit per year (SE = 0.003, p < 0.001). In separate analyses, amyloid, tangles (p-values <0.001) and neocortical Lewy bodies (p = 0.015) were associated with an increased rate of global cognitive decline; macroscopic infarcts and microinfarcts were not. Further, when analyzed simultaneously, amyloid, tangles, and neocortical Lewy bodies remained associated with global cognitive decline (p-values <0.024). Finally, measures of AD were associated with decline in three of four systems, including episodic memory (i.e., tangles), semantic memory (i.e., amyloid and tangles), and working memory (i.e., amyloid). Lewy bodies also were associated with decline in three of four systems (i.e., semantic memory, working memory, and perceptual speed).Interpretation: The neuropathologies of the common causes of dementia, particularly AD and neocortical LBD, are associated with decline in multiple cognitive abilities among older persons without dementia.

Midlife stroke risk and cognitive decline: A 10-year follow-up of the Whitehall II cohort study

BackgroundStroke is associated with an increased risk of dementia. However, it is unclear whether risk of stroke in those free of stroke, particularly in nonelderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in mid life is associated with cognitive decline over 10 years of follow-up. MethodsWe studied 4153 men and 1657 women (mean age, 55.6 years at baseline) from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP), which incorporates age, sex, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over 10 years. Longitudinal associations between FSRP and its components were tested using mixed-effects models, and rates of cognitive change over 10 years were estimated. ResultsHigher stroke risk was associated with faster decline in verbal fluency, vocabulary, and global cognition. For example, for global cognition there was a greater decline in the highest FSRP quartile (−0.25 of a standard deviation; 95% confidence interval: −0.28 to −0.21) compared with the lowest risk quartile (P = .03). No association was observed for memory and reasoning. Of the individual components of FSRP, only diabetes mellitus was associated independently with faster cognitive decline (β = −0.06; 95% confidence interval, −0.01 to 0.003; P = .03). ConclusionElevated stroke risk at midlife is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.

Coevolution of white matter hyperintensities and cognition in the elderly

To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). A total of 150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function). WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures. Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences.

Effect of Cardiovascular and Metabolic Disease on Cognitive Test Performance and Cognitive Change in Older Adults

To examine the effect of cardiovascular and metabolic diseases on initial cognitive test performance and rate of change in three cognitive measures. Prospective cohort study. General practices in six towns throughout Germany. Three thousand three hundred twenty-seven participants aged 75 and older (average 79.7 ± 3.6). Data were collected during home visits every 18 months and included sociodemographic variables, depression, disease status, drug intake, and cognition. Although the presence of transient ischemic attack (TIA) or stroke and diabetes mellitus was related to poor initial cognitive test performance, the presence of those and other far-reaching chronic diseases or a higher disease burden were not related to the rate of change in cognition over time. Diabetes mellitus, stroke and TIA affect cognitive test performance beyond well-known sociodemographic variables and depressive symptoms, although none of these diseases contributed to cognitive decline over time. In practical terms, prevention and diagnosis of cardiovascular and metabolic diseases may be essential to cognitively healthy aging.

Cognitive functions after hemorrhagic stroke

Middle East Current Psychiatry 2011, 18:203–210 Objectives There are scarce data on long-term cognitive outcomes after first-ever hemorrhagic stroke. Aim This study was carried out to determine the frequency of cognitive impairment, no dementia after an intracerebral hemorrhagic stroke and to study their evolution toward dementia (transitions in cognitive state) during a 2-year follow-up. Methods Thirty-five patients with first-ever hemorrhagic strokes and in an age-matched and sexmatched comparison group (nonstroke, n=20) were followed up for 2 years by three serial assessments. Stroke patients at 3, 12, 24 months after discharge were evaluated together with nonstrokes, by an extensive neuropsychological battery and clinical psychiatric interview based on Diagnostic and Statistical Manual of Mental Disease, 4th edition TR criteria. Rates of cognitive change were compared using repeated-measures analyses. Factors associated with incident dementia and cognitive impairment, no dementia at 2 years were determined by multinomial logistic regression. Results The majority of patients (71.4%) were cognitively stable. Fewer cases improved (11.5%) and 71.1% of the stroke cases worsened at the end of the 24-month follow-up. There was impaired cognitive function in nearly all cognitive domains of stroke cases compared with nonstroke cases. Overall, stroke cases showed a statistically significant decline in mini-mental state examination (MMSE), spatial ability, and in the executive function domain; however, there was no improvement in attention nonverbal memory domains. Age at stroke onset was independently associated with cognitive impairment at the 2-year follow-up P=0.03. Conclusion Cognitive evolution 2 years after hemorrhagic stroke is different among patients, but a substantial number of patients remain stable. Additional studies are required to reliably identify individuals at risk for cognitive decline for whom pharmacologic or other therapeutic interventions would be more suitable and who will probably spontaneously improve. Classification of stroke by etiology may be more useful to determine patients at a higher risk of stroke and for its prevention.

An economic evaluation of early assessment for Alzheimer's disease in the United Kingdom

Diagnosing and treating patients with Alzheimer's disease (AD) at an early stage should improve the quality of life of the patient and caregiver. In the United Kingdom, cost-effectiveness of early assessment of individuals presenting with subjective memory complaints and treating those with AD with donepezil was evaluated. A discrete event simulation of AD progression and the effect of treatment interventions was developed. Patient-level data from donepezil trials and a 7-year follow-up registry were used to model correlated longitudinal rates of change in cognition, behavior, and function. Other epidemiological and health services data, including estimates of undiagnosed dementia and delays in diagnosis, were based on published sources. Simulated individuals were followed up for 10 years. In the base-case estimates, 17 patients need to be assessed to diagnose one patient with AD, resulting in an average assessment cost of £4100 ($6000; $1 US = £0.68 UK) per patient diagnosed (2007 cost year). In comparison with a scenario without early assessment or pharmacologic treatment, early assessment reduces health care costs by £3600 ($5300) per patient and societal costs by £7750 ($11,400). Savings are also substantial compared with treatment without early assessment, averaging £2100 ($3100) in health care costs, and £5700 ($8400) in societal costs. Results are most sensitive to estimates of patient care costs and the probability of patients reporting subjective memory complaints. In probabilistic sensitivity analysis, early assessment leads to savings or is highly cost-effective in the majority of cases. Although early assessment has significant up-front costs, identifying AD patients at an early stage results in cost savings and health benefits compared with no treatment or treatment in the absence of early assessment.

Designing clinical trials to test disease-modifying agents: application to the treatment trials of Alzheimer’s disease

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples of such designs. Crucial design parameters such as sample size and the time of treatment switch are important to understand in designing such clinical trials. The purpose of this article is to provide methods to determine sample sizes and time of treatment switch as well as optimum statistical tests of treatment efficacy for clinical trials of disease-modifying agents on AD. A general linear mixed effects model is proposed to test the disease-modifying efficacy of novel therapeutic agents on AD. This model links the longitudinal growth from both the placebo arm and the treatment arm at the time of treatment switch for these in the delayed treatment arm or early withdrawal arm and incorporates the potential correlation on the rate of cognitive change before and after the treatment switch. Sample sizes and the optimum time for treatment switch of such trials as well as optimum test statistic for the treatment efficacy are determined according to the model. Assuming an evenly spaced longitudinal design over a fixed duration, the optimum treatment switching time in a randomized start or a randomized withdrawal trial is half way through the trial. With the optimum test statistic for the treatment efficacy and over a wide spectrum of model parameters, the optimum sample size allocations are fairly close to the simplest design with a sample size ratio of 1:1:1 among the treatment arm, the delayed treatment or early withdrawal arm, and the placebo arm. The application of the proposed methodology to AD provides evidence that much larger sample sizes are required to adequately power disease-modifying trials when compared with those for symptomatic agents, even when the treatment switch time and efficacy test are optimally chosen. The proposed method assumes that the only and immediate effect of treatment switch is on the rate of cognitive change. Crucial design parameters for the clinical trials of disease-modifying agents on AD can be optimally chosen. Government and industry officials as well as academia researchers should consider the optimum use of the clinical trials design for disease-modifying agents on AD in their effort to search for the treatments with the potential to modify the underlying pathophysiology of AD.

MTHFR polymorphisms and cognitive ageing in the ninth decade: the Lothian Birth Cohort 1921

Low blood levels of B vitamins have been implicated in age-associated cognitive impairment. The present study investigated the association between genetic variation in folate metabolism and age-related cognitive decline in the ninth decade of life. Both the 677C>T (rs1801133) polymorphism and the scarcely studied 1298A>C (rs1801131) polymorphism of the MTHFR gene were assessed in relation to cognitive change over 8 years in older community-dwelling individuals. MTHFR genotype was determined in 476 participants of the Lothian Birth Cohort 1921, whose intelligence was measured in childhood in the Scottish Mental Survey of 1932. Cognitive performance on the domains of verbal memory, reasoning and verbal fluency was assessed at mean age of 79 (n = 476) and again at mean ages of 83 (n = 275) and 87 (n = 180). Using linear mixed models, the MTHFR 677C>T and 1298A>C variants were not associated with the rate of cognitive change between 79 and 87 years, neither in the total sample, nor in a subsample of individuals with erythrocyte folate levels below the median. APOE E4 allele carrier status did not interact with MTHFR genotype in affecting change in cognitive performance over 8 years. No significant combined effect of the two polymorphisms was found. In conclusion, MTHFR 677C>T and 1298A>C polymorphisms were not associated with individual change in cognitive functioning in the ninth decade of life. Although polymorphisms in the MTHFR gene may cause disturbances in folate metabolism, they do not appear to be accompanied by changes in cognitive functioning in old age.

Onset and Rate of Cognitive Change Before Dementia Diagnosis: Findings From Two Swedish Population-Based Longitudinal Studies

We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.

Higher mental stimulation at work is associated with improved cognitive functioning in both young and older workers

The study examined whether mental stimulation received in the workplace positively affects cognitive functioning and rate of cognitive change. Data taken from the VISAT (ageing, health and work) longitudinal study concerned 3237 workers who were seen three times (in 1996, 2001 and 2006) and who were aged between 32 and 62 years at baseline. Measures of cognitive stimulation both at work and outside work were available at baseline. Cognitive efficiency was assessed on the three occasions through episodic verbal memory, attention and processing speed tests. Greater cognitive stimulation (at work and outside work) was associated with higher levels of cognitive functioning and a more favourable change over the 10-year follow-up. These results were obtained after adjustment for age, education, sex and a variety of medical, physical and psychosocial confounders. The study thus supports the hypothesis that exposure to jobs that are mentally demanding and that offer learning opportunities increases the level of cognitive functioning and possibly attenuates age-related decline. Statement of Relevance: The effect of occupational activity on cognitive functioning is under-researched. This paper reports results from a substantive longitudinal study, with findings indicating that exposure to jobs that are mentally demanding are beneficial in increasing levels of cognitive functioning and possibly attenuating age-related decline.

Physical Frailty Is Associated with Incident Mild Cognitive Impairment in Community‐Based Older Persons

To test the hypothesis that physical frailty is associated with risk of mild cognitive impairment (MCI). Prospective, observational cohort study. Approximately 40 retirement communities across the Chicago metropolitan area. More than 750 older persons without cognitive impairment at baseline. Physical frailty, based on four components (grip strength, timed walk, body composition, and fatigue), was assessed at baseline, and cognitive function was assessed annually. Proportional hazards models adjusted for age, sex, and education were used to examine the association between physical frailty and the risk of incident MCI, and mixed effect models were used to examine the association between frailty and the rate of change in cognition. During up to 12 years of annual follow-up, 305 of 761 (40%) persons developed MCI. In a proportional hazards model adjusted for age, sex, and education, physical frailty was associated with a high risk of incident MCI, such that each one-unit increase in physical frailty was associated with a 63% increase in the risk of MCI (hazard ratio=1.63; 95% confidence interval=1.27-2.08). This association persisted in analyses that required MCI to persist for at least 1 year and after controlling for depressive symptoms, disability, vascular risk factors, and vascular diseases. Furthermore, a higher level of physical frailty was associated with a faster rate of decline in global cognition and five cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, and visuospatial abilities). Physical frailty is associated with risk of MCI and a rapid rate of cognitive decline in aging.

HIV-associated brain dysfunction in the era of HAART

Studies conducted following the advent of highly active antiretroviral therapy (HAART) over a decade ago demonstrated dramatic neurocognitive improvements among HIV-infected people,1 leading to initial optimism that brain dysfunction secondary to HIV might be eradicated. Yet neurocognitive disturbances continue to occur,2,3 and may be continuing to evolve in the HAART era,4 with the possibility that the proviral DNA remains despite treatment.5 There are still many important questions about the relationship between HIV-associated neurocognitive impairments and antiretroviral (ARV) treatment. The study by Cysique and colleagues6 provides insights into the timeline and biomarkers associated with cognitive changes following ARV initiation. Rapid cognitive improvements occurred within the first 12 weeks, which continued more gradually throughout the 48-week study period. The results provide a preliminary reference for the degree and rate of cognitive change that might be expected, and point to the potential value of short-term cognitive improvements as an independent marker of treatment outcome. Clinicians may then consider adjustment to treatment regimens if expected cognitive improvements are not observed despite …

Intelligence and Medial Temporal Lobe Function in Older Adults: A Functional MR Imaging–Based Investigation

The influence of general intelligence and formal education on functional MR imaging (fMRI) activation has not been thoroughly studied in older adults. Although these factors could be controlled for through study design, this approach makes sample selection more difficult and reduces power. This study was undertaken to examine our hypothesis that intelligence and education would impact medial temporal lobe (MTL) fMRI responses to an episodic memory task in healthy elderly subjects. Thirty-six women and 38 men, 50-83 years of age (mean, 63.4 +/- 7.9 years), completed an auditory paired-associates paradigm in a 1.5T magnet. The amplitude and volume of fMRI activation for both the right and left MTLs and MTL subregions were correlated with the intelligence quotients (IQs) and educational levels by using Pearson correlation coefficient tests and regression analyses. The participants' mean estimated full scale IQ and verbal IQ scores were 110.4 +/- 7.6 (range, 92-123) and 108.9 +/- 8.7 (range, 88-123), respectively. The years of education showed a mean of 16.1 +/- 3.2 years (range, 8-25 years). The paradigm produced significant activation in the MTL and subregions. However, the volume and amplitude of activation were unrelated to either IQ or years of schooling in men and/or women. We found no evidence of an effect of IQ or education on either the volume or amplitude of fMRI activation, suggesting that these factors do not necessarily need to be incorporated into study design or considered when evaluating other group relationships with fMRI.

Delirium accelerates cognitive decline in Alzheimer disease

To examine the impact of delirium on the trajectory of cognitive function in a cohort of patients with Alzheimer disease (AD). A secondary analysis of data collected from a large prospective cohort, the Massachusetts Alzheimer's Disease Research Center's patient registry, examined cognitive performance over time in patients who developed (n = 72) or did not develop (n = 336) delirium during the course of their illnesses. Cognitive performance was measured by change in score on the Information-Memory-Concentration (IMC) subtest of the Blessed Dementia Rating Scale. Delirium was identified using a previously validated chart review method. Using linear mixed regression models, rates of cognitive change were calculated, controlling for age, sex, education, comorbid medical diagnoses, family history of dementia, dementia severity score, and duration of symptoms before diagnosis. A significant acceleration in the slope of cognitive decline occurs following an episode of delirium. Among patients who developed delirium, the average decline at baseline for performance on the IMC was 2.5 points per year, but after an episode of delirium there was further decline to an average of 4.9 points per year (p = 0.001). Across groups, the rate of change in IMC score occurred about three times faster in those who had delirium compared to those who did not. Delirium can accelerate the trajectory of cognitive decline in patients with Alzheimer disease (AD). The information from this study provides the foundation for future randomized intervention studies to determine whether prevention of delirium might ameliorate or delay cognitive decline in patients with AD.

The role of occupational complexity in trajectories of cognitive aging before and after retirement.

We examined the association between complexity of the main lifetime occupation and changes in cognitive ability in later life. Data on complexity of work with data, people, and things and on 4 cognitive factors (verbal, spatial, memory, and speed) were available from 462 individuals in the longitudinal Swedish Adoption/Twin Study of Aging. Mean age at the first measurement wave was 64.3 years (SD = 7.2), and 65% of the sample had participated in at least three waves of data collection. Occupational complexity with people and data were both correlated with cognitive performance. Individuals with more complex work demonstrated higher mean performance on the verbal, spatial, and speed factors. Latent growth curve analyses indicated that, after correcting for education, only complexity with people was associated with differences in cognitive performance and rate of cognitive change. Continued engagement as a result of occupational complexity with people helped to facilitate verbal function before retirement, whereas a previous high level of complexity of work with people was associated with faster decline after retirement on the spatial factor.

Inflammation and Rate of Cognitive Change in High-Functioning Older Adults

Inflammatory proteins including interleukin-6 (IL-6) and C-reactive protein (CRP) have been associated with incident cognitive impairment, but little research has addressed their effects on the rate of cognitive change, and findings are mixed. The purpose of this study was to examine the relationship between serum levels of IL-6 and CRP and the rate of cognitive change across a range of cognitive domains in a sample of healthy older persons. Growth curve analysis was performed on data from the MacArthur Study of Successful Aging, a longitudinal cohort study of high-functioning older adults aged 70-79 years at baseline in 1988 and reinterviewed in 1991 and 1995 (N = 851). Individual growth curve parameters were derived from baseline and follow-up performance in abstraction, language, spatial ability, verbal recall, spatial recognition, and global cognitive function based on age, IL-6, CRP, and covariates. Cross-sectionally, there is a generally linear negative relationship between inflammation and cognition, such that higher levels of inflammation are associated with lower levels of baseline cognitive function. After controlling for potential confounders, there was no effect of inflammation on baseline cognitive function or the rate of longitudinal cognitive change. However, persons in the top tertile on IL-6 were at an increased risk of incident declines on the Short Portable Mental Status Questionnaire (SPMSQ). Although high levels of inflammation are associated with incident cognitive impairment, these results do not generalize to the full range of cognitive changes, where the role of inflammation appears to be marginal.

Poster 36: Cognitive Functioning in Older Adults Over Time: Effect of Traumatic Brain Injury and APOE ε4 Allele Status

Objective: To determine the relative contributions of traumatic brain injury (TBI) and APOE ε4 allele status to cognitive functioning over time in people 55 years and older. Design: Observational. Setting: Research center at an urban medical center. Participants: 54 subjects with TBI and 41 participants with no history of TBI. Interventions: Not applicable. Main Outcome Measures: Factor scores measuring memory, processing speed, verbal fluency, and executive functioning derived from standardized neuropsychologic tests. Results: The neuropsychologic battery was administered twice postinjury, with a mean interval of 31.9±12 months between assessments. An initial analysis of covariance (ANCOVA), controlling for age and education, comparing the positive and negative APOE ε4 status groups yielded no significant differences between groups at either time point for any of the factors. However, when the TBI and non-TBI groups were compared, a main effect for group was found on the processing speed factor, with the TBI group performing worse than the non-TBI group at both time points (P<.001). ANCOVAs comparing both the positive and negative APOE ε4 status among TBI and non-TBI groups showed no significant between-group differences in cognitive functioning over time. Conclusions: In this study, older adults with TBI did not exhibit different rates of cognitive change over time from non-TBI counterparts and APOE ε4 status did not contribute significantly to changes in cognitive function. However, older adults with TBI did have greater cognitive impairment than their non-TBI counterparts at both assessment points on a factor measuring processing speed.