Practice effects persist over two decades of cognitive testing: Implications for longitudinal research

Evidence is accumulating from in vitro and rodent studies that vitamin K plays a role in brain and could have a positive effect on cognitive function, especially during aging. The present study examined cross‐sectional associations between vitamin K status and cognitive performance in 320 cognitively‐healthy men and women aged 70–85 y from the Québec Longitudinal Study on Nutrition and Successful Aging. Vitamin K status was measured as serum phylloquinone concentrations. Verbal and non‐verbal episodic memory, executive functions, and speed of processing were assessed using 13 cognitive scores from 6 tests. The median serum phylloquinone concentration was 1.06 nmol/L (range, 0.08–23.57 nmol/L). After adjustment for covariates including diet quality and serum lipid profile, higher serum phylloquinone concentration (log‐transformed) was associated with better cognitive scores (Z‐transformed) on the second (β = 0.47; 95% CI = 0.13 to 0.82), the third (β = 0.41; 95% CI = 0.06 to 0.75), and the 20‐min delayed (β = 0.47; 95% CI = 0.12 to 0.82) trials of the RL/RI‐16 Free and Cued Recall Task, a test of verbal episodic memory. No associations were found with non‐verbal episodic memory, executive functions, and speed of processing. Overall, our study provides evidence for a role of vitamin K in episodic verbal memory among healthy older adults. This research was supported by the Canadian Institutes of Health Research.

Abstract. Individuals between the ages of 18 and 94 (N = 326) completed a battery of episodic memory tasks, as well as several measures of spatial visualization. A female advantage in verbal episodic memory and a male advantage in spatial and visual episodic memory were observed. Mediation analyses provided evidence that performance on spatial visualization tasks greatly influences the magnitude of the effect for sex differences among the different episodic memory constructs. In particular, the spatial visualization construct fully mediated the relationship between sex and episodic spatial memory performance. Further, when spatial visualization was included as a mediator in the model the relationship between sex and episodic verbal memory increased, and the relationship between sex and episodic visual memory reversed, such that women scored higher than men.

Introduction: Cognitive function is an important outcome measure in patients with brain tumor, providing information about the patient’s clinical situation, treatment effects and possible progressive disease. The aim of this longitudinal study was to evaluate effects of the currently used radiation and chemotherapy treatment on cognitive function and to investigate associations between cognitive function at baseline and progression as well as overall survival.Methods: 32 patients newly diagnosed with malignant glioma were evaluated at baseline with CNS Vital Signs (CNS-VS), a computerized standardized neuropsychological test battery, prior to arc-based radiotherapy and concomitant chemotherapy with Temozolomide. CNS-VS measures the cognitive functions known to be affected in patients with brain tumor, covering nine cognitive domains. Follow-up cognitive evaluations were performed in 26 patients after 3.5 months and in 13 patients 1 year after treatment start.Results: Overall cognitive scores were lower in the studied patient cohort at baseline compared to standardized domain scores. At 3.5 months follow-up cognitive functioning was slightly decreased, but only in 1/9 cognitive domains – visual memory – where significant changes were found compared to baseline test results. Similarly, at 12 months follow-up no significant changes in cognitive test results were seen compared to baseline examination, except for a decrease in the visual memory domain. In relation to early progression, the most significant cognitive deficits were dysfunctional visual memory and low executive functioning at baseline. Low executive function at baseline correlated most significantly with shorter overall survival.Conclusion: The present study suggests that the currently used arc-based radiotherapy and chemotherapy might affect cognitive function less negatively than previously described during treatment and in the first year after treatment in malignant glioma patients. In general, a high cognitive test score at baseline was associated with longer time to progression and with longer survival.

Genome-wide association studies are instrumental in quantifying genetic influences underlying Alzheimer's disease (AD), and applications of polygenic scores derived from association studies have already shed light on early disease pathology. For example, AD polygenic scores (AD-PGS) are associated with amnestic mild cognitive impairment (MCI) diagnoses in midlife. What remains unclear is how AD-PGS relate to objectively measured cognitive changes across midlife. Moreover, executive function abilities have been somewhat neglected despite prominent executive impairments in MCI and AD. Here we tested the hypothesis that an AD-PGS would be associated with executive function and episodic memory changes across late midlife.We examined 1412 men in the Vietnam Era Twin Study of Aging (VETSA) who were cognitively normal at their first assessment and had up to 3 cognitive assessments across 10-12 years (mean ages 56, 62, and 68). Latent growth models of executive function were based on 6 tasks spanning inhibition, shifting, and working memory subdomains and growth models of episodic memory were based on 7 subtests from the Logical Memory, Visual Reproductions, and California Verbal Learning tests. The AD-PRS (Lambert et al. 2013) significantly differentiated MCI and cognitively normal participants in earlier VETSA investigations.Latent growth models of executive function and memory indicated that, compared to baseline performance (i.e., intercept at mean age 56), 10-year variability in cognitive change was comparatively larger for executive function (e.g., slope variance/intercept variance ratio=39% for executive function, 22% for memory). Importantly, individuals with higher AD-PGS had sharper declines in executive functioning (r= -.24, 95% CI [-.41, -.08]) but not episodic memory (r= -.11, 95% CI [-.25, .04]). Baseline executive function (r=.00) and memory (r=-.02) were not associated with PD-PGS.AD genetic risk was associated with executive function changes, but not episodic memory changes, across midlife. These findings highlight the importance of considering executive function changes in midlife, especially for predicting disease progression and AD biology. Executive functions are one of the first cognitive abilities to decline in midlife in normal aging. This study is among the first to demonstrate that this decline also relates to AD genetic influences.

Cognitive factor structure and measurement invariance between healthy controls and patients with major depressive disorder

Previous studies in pre-clinical Alzheimer’s disease have found associations between amyloid and practice effects. Additionally, studies within our research group have found associations between practice effects and cognitive tests, including language-based measures, as well as associations between language-based measures and Alzheimer’s disease biomarkers. The purpose of this study is to bridge the gaps between these areas to further understand how practice effects may or may not explain additional variance between biomarker groups and to expand on current literature by incorporating tau status into these models. Our study had three main aims: (1) determine which of our proposed operationalizations of practice effects performed best, (2) explore the impact of amyloid on practice effects and (3) explore the impact of combined amyloid and tau status on practice effects for language-based measures: the proper names composite from the Logical Memory story recall task, as well as the total score, animal fluency, and letter fluency tasks. Participants from the Wisconsin Registry for Alzheimer’s Prevention study with amyloid positron emission tomography (PET) scans and item-level Logical Memory data were included in these analyses (n = 442); the Aim 3 subset, requiring both amyloid and tau PET scans, included n = 397. Linear mixed effects models were used to explore our aims; for Aim 1 we utilized Akaike information criteria (AIC) to determine which operationalization performed best and for Aims 2 and 3 we used an interaction of biomarker * practice to determine if biomarker status(es) moderated the impact of practice on our measures of interest. Comparing the base model AIC to the models including practice showed that inclusion improved model fit for all outcomes Proper names from Logical Memory and the total score of Logical Memory showed a moderating effect of amyloid status on practice effects. Sensitivity analyses indicated that it may be age that is driving the association, however. A similar pattern was seen upon testing amyloid/tau (A/T) status and practice effect moderation on our outcomes, such that participants who were A+T+ did not appear to benefit from practice as much as the A−T− participants did. Future studies should seek to tease apart the intertwined impacts of age, practice and cognitive decline.

BackgroundVascular cognitive impairment and dementia (VCID) is the second most common cause of cognitive impairment in older adults. However, identifying reliable biomarkers for VCID remains challenging. Cerebral Oxygen‐extraction‐fraction (OEF), a key hemodynamic parameter of brain function, has been found elevated in cerebrovascular disorders such as carotid steno‐occlusive disease and ischemic stroke. In this study, we employed a novel non‐invasive, non‐contrast MRI technique to measure OEF in a VCID‐enriched cohort. We hypothesized that elevated OEF would be associated with worse cognition and vascular risk factors in this cohort.MethodEighty‐seven older adults were enrolled from the MarkVCID2 cohort, which is enriched for vascular risk factors and brain white matter lesions and/or microbleeds. Table 1 summarizes the demographic information. Cortical and subcortical OEF values were measured using a technique called accelerated‐T2‐relaxation‐under‐phase‐contrast (aTRUPC) MRI. A comprehensive neuropsychological battery provided five cognitive domain scores: episodic memory, executive function, processing speed, attention, and language. A composite cognitive score was derived by averaging Z‐scores across all domains. A composite vascular‐risk‐score (VRS) was obtained from the number of vascular risk factors present in each patient. Linear regression models were used to analyze the associations between regional OEF, cognitive scores, and VRS.ResultFigure 1 displays representative MRI . OEF was negatively correlated with the composite cognitive score (cortical: β=‐0.035±0.010, p = 0.0012; subcortical: β=‐0.028±0.011, p = 0.0093). We next examined the associations between domain‐specific Z‐scores and regional OEF, as summarized in Table 2. After Bonferroni correction, only executive function showed a significant negative correlation with OEF (cortical: β=‐0.044±0.012, p = 0.0043; subcortical: β=‐0.038±0.012, p = 0.030). Notably, elevated OEF was associated with declines in executive function (characteristic of VCID) but not with declines in episodic memory (characteristic of Alzheimer’s disease). These findings suggest that elevated OEF is primarily related to VCID rather than Alzheimer’s dementia. Additionally, we observed that OEF was positively associated with VRS (cortical: β=1.451±0.610, p = 0.020; subcortical: β=1.335±0.605, p = 0.030), further supporting the relationship between elevated OEF and neurovascular pathology.ConclusionWe showed that elevated cortical and subcortical OEF was associated with poorer cognition (particularly in executive function) among older adults with vascular risks, suggesting that OEF may be a useful biomarker for VCID.

Episodic memory and executive function are two cognitive domains that have been studied extensively in older adults and have been shown to decline in normally-aging older individuals. However, one of the problems with characterizing cognitive changes in longitudinal studies has been separating effects attributable to normal aging from effects created by repeated testing or practice. In the present study, 166 people aged 65 and older were enrolled over several years and tested at least 3 times at variable intervals (M = 3.2 yrs). The cognitive measures were composite scores. Each composite was made up of five neuropsychological tests, previously identified through factor analysis. For one pair of composite scores, variance attributable to age was removed from each subtest through regression analyses before z-scores were computed, creating two age-corrected composites. A second pair of composites were not age-corrected. Using linear mixed-effects models, we first explored retest effects for each cognitive domain, independent of age, using the age-corrected composites. We then modeled aging effects using the age-uncorrected composites after subtracting out retest effects. Results indicated significant retest effects for memory but not for executive function, such that memory performance improved across the three testing sessions. When these practice effects were removed from the age-uncorrected data, effects of aging were evident for both executive and memory function with significant declines over time. We also explored several individual difference variables including sex, IQ, and age at the initial testing session and across time. Although sex and IQ affected performance on both cognitive factors at the initial test, neither was related to practice effects, although young-older adults tended to benefit from practice to a greater extent than old-older adults. In addition, people with higher IQs showed slower age-related declines in memory, but no advantages in executive function. These findings suggest that (a) aging affects both memory and executive function similarly, (b) higher IQ, possibly reflecting cognitive reserve, may slow age-related declines in memory, and (c) practice through repeated testing enhances performance in memory particularly in younger-older adults, and may therefore mask aging effects if not taken into account.

Prior work has shown that certain modifiable health, Alzheimer's disease (AD) biomarker, and demographic variables are associated with cognitive performance. However, less is known about the relative importance of these different domains of variables in predicting longitudinal change in cognition. Identify novel relationships between modifiable physical and health variables, AD biomarkers, and slope of cognitive change over two years in a cohort of older adults with mild cognitive impairment (MCI). Metrics of cardiometabolic risk, stress, inflammation, neurotrophic/growth factors, and AD pathology were assessed in 123 older adults with MCI at baseline from the Alzheimer's Disease Neuroimaging Initiative (mean age = 73.9; SD = 7.6; mean education = 16.0; SD = 3.0). Partial least squares regression (PLSR)-a multivariate method which creates components that best predict an outcome-was used to identify whether these physiological variables were important in predicting slope of change in episodic memory or executive function over two years. At two-year follow-up, the two PLSR models predicted, respectively, 20.0% and 19.6% of the variance in change in episodic memory and executive function. Baseline levels of AD biomarkers were important in predicting change in both episodic memory and executive function. Baseline education and neurotrophic/growth factors were important in predicting change in episodic memory, whereas cardiometabolic variables such as blood pressure and cholesterol were important in predicting change in executive function. These data-driven analyses highlight the impact of AD biomarkers on cognitive change and further clarify potential domain specific relationships with predictors of cognitive change.

BackgroundA key component of cognitive aging is episodic memory decline. Here we examined to which degree structural integrity of (para)limbic cortex and amyloid load contribute to normal episodic memory variation in subjects between 50 and 80 years old using mediation analysis. The main hypothesis was that the effect of age on episodic memory would be mediated through hippocampal volume.Method180 community‐recruited cognitively intact older adults belonging to the Flemish Prevent Alzheimer's Disease Cohort KU Leuven (F‐PACK) cohort had cognitive test scores within norms as inclusion criterion, genotyping (APOE ε4 and BDNF), MRI and [18F]flutemetamol‐PET. Factor analysis was applied to determine the latent structure in the neuropsychological dataset. The primary factor (variance explained: 23%, Eigenvalue: 2.26) mainly contained episodic memory test scores: Buschke selective reminding (loadings: learning: 0.83, delayed‐recall: 0.96) and Rey Auditory Verbal Learning Test (0.60). Structural T1‐weigthed MRI were processed using voxel‐based morphometry. Hippocampal, entorhinal, perirhinal and parahippocampal volumes were derived by intersecting the modulated gray matter with Brainnetome parcellations. Amyloid load was quantified in a composite neocortical volume on [18F]flutemetamol SUVR with cerebellar grey matter reference. Linear regressions or Mann‐Whitney U tests investigated associations with episodic memory, which were further analyzed with bootstrapped mediation (R‐package ‘lavaan’).ResultHigher age was negatively related to lower episodic memory scores (β=‐0.066, p<0.001), to lower hippocampal volume (β=‐0.005, p<0.001) and to lower entorhinal cortex volume (β=‐0.003, p<0.001). Lower hippocampal volume (β=3.80, p=0.0004) as well as entorhinal cortex volume (β=3.67, p<0.001) were related to lower episodic memory. There was no significant correlation of amyloid nor a genetic effect regarding age or episodic memory (p>0.12). Hence, we did not include amyloid or genotypes in further analyses. In the mediation analysis, hippocampal volume did not mediate the relation between age and episodic memory (Figure 1A). By contrast, entorhinal cortex volume did mediate the relation between age and episodic memory, however the direct path coefficient was also significant (Figure 1B). No significant indirect effects were found in the path analysis for the perirhinal cortex or parahippocampus (p>0.14).ConclusionThe effect of age on episodic memory is partly mediated by entorhinal rather than hippocampal volume in cognitive aging.

Lifestyle and the aging brain: interactive effects of modifiable lifestyle behaviors and cognitive ability in men from midlife to old age

Association between the self-reported duration and quality of sleep and cognitive function among middle-aged and older adults in China

Longitudinal study of the effects of occupational aluminium exposure on workers’ cognition

Thirty-five patients with probable Alzheimer's disease who were enrolled in an experimental drug trial of linopirdine underwent repeated testing that included recording the middle latency auditory evoked potential (MLAEP), the Mini-Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCOG). Patients lacking the P1 component of the MLAEP exhibited a significantly greater decline in cognitive function as measured by the ADASCOG over 56 weeks. This decline appeared to be due to a less robust practice effect, which was maximal in all patients at 16 weeks. At the end of 56 weeks the entire group of patients was near baseline with respect to the ADASCOG. This lack of the annualized decline expected from other longitudinal studies may be explained by practice and placebo effects. The MMSE did not exhibit a practice effect and showed the expected decline in scores.

Cognitive deficits in recent-onset and chronic schizophrenia