Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

INTRODUCTION: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume. DISCUSSION: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. HIGHLIGHTS: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative.

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Aging Enhances Neural Activity in Auditory, Visual, and Somatosensory Cortices: The Common Cause Revisited.

In humans, age-related declines in vision, hearing, and touch coincide with changes in amplitude and latency of sensory-evoked potentials. These age-related differences in neural activity may be related to a common deterioration of supra-modal brain areas (e.g., PFC) that mediate activity in sensory cortices or reflect specific sensorineural impairments that may differ between sensory modalities. To distinguish between these two possibilities, we measured neuroelectric brain activity while 37 young adults (18-30 years, 18 males) and 35 older adults (60-88 years, 20 males) were presented with a rapid randomized sequence of lateralized auditory, visual, and somatosensory stimuli. Within each sensory domain, we compared amplitudes and latencies of sensory-evoked responses, source activity, and functional connectivity (via phase-locking value) between groups. We found that older adults' early sensory-evoked responses were greater in amplitude than those of young adults in all three modalities, which coincided with enhanced source activity in auditory, visual, and somatosensory cortices. Older adults also showed stronger neural synchrony than young adults between superior prefrontal and sensory cortices; and in older adults, the degree of phase synchrony was positively correlated with the magnitude of source activity in sensory areas. Critically, older adults who showed enhanced neural activity in one sensory domain also showed enhanced activity in other modalities. Together, these findings support the common cause hypothesis of aging and highlight the role of prefrontal regions in exerting top-down control over sensory cortices.SIGNIFICANCE STATEMENT A prominent theory of aging posits that age-related declines in sensory processing across domains are related to a single common neurobiological mechanism. However, the neural evidence supporting this common cause hypothesis has remained elusive. Our study revealed robust age-related changes in three sensory domains across a range of neural metrics. Importantly, older adults who showed increased neural activity within one sensory domain also showed enhanced neural activity in the other two sensory modalities. No such relation among activity in sensory cortices was observed in young adults. Age-related increases in neural activity in sensory cortices coincided with enhanced neural synchrony between the PFC and sensory cortices, underlining the importance of the PFC in regulating sensory processing.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Relationships between neuropsychiatric symptoms and cognitive profiles in Alzheimer's disease and related syndromes.

OBJECTIVES: To investigate the rate of occurrence of neuropsychiatric symptoms (NPS) and their relationship with age, sex and cognitive performance in subjects with Alzheimer's disease and related dementias (Alzheimer's disease and related dementias [ADRD]). METHODS: This is a retrospective matched case-control study. Data from memory clinic patients included demographic information presence of NPS, and cognitive testing of Orientation, Immediate and Delayed Memory, Visuospatial Function, Working Memory, Attention, Executive Control and Language. Participants were Individuals with subjective cognitive impairment (n = 352), mild cognitive impairment (MCI) (n = 369), vascular MCI (n = 80), Alzheimer's disease (n = 147), vascular dementia (n = 41), mixed dementia (n = 33), and healthy controls (n = 305). Logistic regression was used to investigate the relationship between the presence of NPS, age and sex. A generalised additive model was used to investigate the relationship between presence of NPS, age and cognitive impairment. Analysis of variance was used to investigate differences in cognition between younger and older groups with and without NPS. RESULTS: We found an increased likelihood of occurrence of NPS in younger individuals and females across cohorts. Anxiety, depression, agitation, and apathy were associated with higher overall rate of NPS. We also found that individuals under 65 years of age with NPS had worse cognitive scores than their counterpart without NPS. CONCLUSION: The younger group with ADRD and NPS had lower cognitive scores, probably reflecting more aggressive neurodegenerative disease. Further work will be needed to elicit the degree to which imaging or mechanistic abnormalities distinguish this group.

Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function.

OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Small and Large Magnetic Resonance Imaging-Visible Perivascular Spaces in the Basal Ganglia of Parkinson's Disease Patients.

BACKGROUND: Although previously thought to be asymptomatic, recent studies have suggested that magnetic resonance imaging-visible perivascular spaces (PVS) in the basal ganglia (BG-PVS) of patients with Parkinson's disease (PD) may be markers of motor disability and cognitive decline. In addition, a pathogenic and risk profile difference between small (≤3-mm diameter) and large (>3-mm diameter) PVS has been suggested. OBJECTIVE: The aim of this study was to examine associations between quantitative measures of large and small BG-PVS, global cognition, and motor/nonmotor features in a multicenter cohort of patients with PD. METHODS: We performed a cross-sectional study examining the association between large and small BG-PVS with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-IV and cognition (Montreal Cognitive Assessment) in 133 patients with PD enrolled in the Ontario Neurodegenerative Disease Research Initiative study. RESULTS: Patients with PD with small BG-PVS demonstrated an association with MDS-UPDRS Parts I (P = 0.008) and II (both P = 0.02), whereas patients with large BG-PVS demonstrated an association with MDS-UPDRS Parts III (P < 0.0001) and IV (P < 0.001). BG-PVS were not correlated with cognition. CONCLUSIONS: Small BG-PVS are associated with motor and nonmotor aspects of experiences in daily living, while large BG-PVS are associated with the motor symptoms and motor complications. © 2022 International Parkinson and Movement Disorder Society.

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative.

OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.

Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury.

OBJECTIVE: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. PARTICIPANTS: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. METHODS: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. RESULTS: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. CONCLUSION: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.

Parkinson's Disease, NOTCH3 Genetic Variants, and White Matter Hyperintensities.

BACKGROUND: White matter hyperintensities (WMH) on magnetic resonance imaging may influence clinical presentation in patients with Parkinson's disease (PD), although their significance and pathophysiological origins remain unresolved. Studies examining WMH have identified pathogenic variants in NOTCH3 as an underlying cause of inherited forms of cerebral small vessel disease. METHODS: We examined NOTCH3 variants, WMH volumes, and clinical correlates in 139 PD patients in the Ontario Neurodegenerative Disease Research Initiative cohort. RESULTS: We identified 13 PD patients (~9%) with rare (<1% of general population), nonsynonymous NOTCH3 variants. Bayesian linear modeling demonstrated a doubling of WMH between variant negative and positive patients (3.1 vs. 6.9 mL), with large effect sizes for periventricular WMH (d = 0.8) and lacunes (d = 1.2). Negative correlations were observed between WMH and global cognition (r = -0.2). CONCLUSION: The NOTCH3 rare variants in PD may significantly contribute to increased WMH burden, which in turn may negatively influence cognition. © 2020 International Parkinson and Movement Disorder Society.

Methods for Improving Screening for Vascular Cognitive Impairment Using the Montreal Cognitive Assessment.

BACKGROUND: Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke. AIM: We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery. METHODS: We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone. RESULTS: Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%. CONCLUSIONS: The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.

The utility of multivariate outlier detection techniques for data quality evaluation in large studies: an application within the ONDRI project.

BACKGROUND: Large and complex studies are now routine, and quality assurance and quality control (QC) procedures ensure reliable results and conclusions. Standard procedures may comprise manual verification and double entry, but these labour-intensive methods often leave errors undetected. Outlier detection uses a data-driven approach to identify patterns exhibited by the majority of the data and highlights data points that deviate from these patterns. Univariate methods consider each variable independently, so observations that appear odd only when two or more variables are considered simultaneously remain undetected. We propose a data quality evaluation process that emphasizes the use of multivariate outlier detection for identifying errors, and show that univariate approaches alone are insufficient. Further, we establish an iterative process that uses multiple multivariate approaches, communication between teams, and visualization for other large-scale projects to follow. METHODS: We illustrate this process with preliminary neuropsychology and gait data for the vascular cognitive impairment cohort from the Ontario Neurodegenerative Disease Research Initiative, a multi-cohort observational study that aims to characterize biomarkers within and between five neurodegenerative diseases. Each dataset was evaluated four times: with and without covariate adjustment using two validated multivariate methods - Minimum Covariance Determinant (MCD) and Candès' Robust Principal Component Analysis (RPCA) - and results were assessed in relation to two univariate methods. Outlying participants identified by multiple multivariate analyses were compiled and communicated to the data teams for verification. RESULTS: Of 161 and 148 participants in the neuropsychology and gait data, 44 and 43 were flagged by one or both multivariate methods and errors were identified for 8 and 5 participants, respectively. MCD identified all participants with errors, while RPCA identified 6/8 and 3/5 for the neuropsychology and gait data, respectively. Both outperformed univariate approaches. Adjusting for covariates had a minor effect on the participants identified as outliers, though did affect error detection. CONCLUSIONS: Manual QC procedures are insufficient for large studies as many errors remain undetected. In these data, the MCD outperforms the RPCA for identifying errors, and both are more successful than univariate approaches. Therefore, data-driven multivariate outlier techniques are essential tools for QC as data become more complex.

Response Time Consistency Is an Indicator of Executive Control Rather than Global Cognitive Ability.

OBJECTIVES: Intraindividual variability increases with age, but the relative strength of association with cognitive domains is still unclear. The objective of this study was to examine the relation between cognitive domains and the shape and spread of response time (RT) distributions as indexed by intraindividual standard deviation (ISD), and ex-Gaussian parameters (µ, σ, τ). METHODS: Healthy adults (40 young [aged 18-30 years], 40 young-old [aged 65-74 years], and 41 old-old [aged 75-85 years]) completed neuropsychological testing and a touch-screen attention task from which ISD and ex-Gaussian parameters were derived. The relation between RT performance and cognitive domains (memory, processing speed, executive functioning) was examined with structural equation modeling (SEM), and the predictive power of RT distribution indices over age was investigated with linear regression. RESULTS: ISD, µ, and τ, but not σ, showed a linear increase with age group. An SEM showed that independent of age, τ was most strongly associated with executive functioning, while µ exhibited less critical associations. Linear regression indicated that µ and τ explained a significant portion of variance in processing speed and executive ability in addition to age group. Memory was more parsimoniously predicted by age, without any significant contribution of ex-Gaussian parameters. CONCLUSIONS: The findings suggest that exceptionally slow responses convey attention lapses through wavering of cognitive control, which strongly correspond to executive functioning tests. General slowing and extremely slow responses predicted processing speed and executive performance beyond age group, indicating that RT metrics are sensitive to differences in cognitive ability. (JINS, 2018, 24, 456-465).

Fit for Dialysis: a qualitative exploration of the impact of a research-based film for the promotion of exercise in hemodialysis.

BACKGROUND: Exercise improves functional outcomes and quality of life of older patients with end-stage renal disease undergoing hemodialysis. Yet exercise is not promoted as part of routine care. Health care providers and family carers rarely provide encouragement for patients to exercise, and the majority of older patients remain largely inactive. There is thus the need for a shift in the culture of hemodialysis care towards the promotion of exercise for wellness, including expectations of exercise participation by older patients, and encouragement by health care providers and family carers. Film-based educational initiatives hold promise to effect cultures of best practice, but have yet to be utilized in this population. METHODS: We developed a research-based film, Fit for Dialysis, to promote exercise for wellness in hemodialysis care. Using a qualitative approach, we evaluated the effects that resulted from engagement with this film (e.g. knowledge/attitudes regarding the importance of exercise-based principles of wellness) as well as the generative mechanisms of these effects (e.g. realism, aesthetics). We also explored the factors related to patients, family carers, and health care providers that influenced engagement with the film, and the successful uptake of the key messages of Fit for Dialysis. We conducted qualitative interviews with 10 patients, 10 health care providers, and 10 family carers. Data were analyzed using thematic analysis. RESULTS: The film was perceived to be effective in increasing patients', family carers' and health care providers' understanding of the importance of exercise and its benefits, motivating patients to exercise, and in increasing encouragement by family carers and health care providers of patient exercise. Realism (e.g. character identification) and aesthetic qualities of the film (e.g. dialogue) were identified as central generative mechanisms. CONCLUSIONS: Fit for Dialysis is well-positioned to optimize the health and wellbeing of older adults undergoing hemodialysis. TRIAL REGISTRATION: NCT02754271 ( ClinicalTrials.gov ), retroactively registered on April 21, 2016.

Effects of divided attention at encoding and retrieval: Further data.

Division of attention (DA) at the time of learning has large detrimental effects on subsequent memory performance, but DA at retrieval has much smaller effects (Baddeley, Lewis, Eldridge, & Thomson, 1984, Journal of Experimental Psychology: General, 113, 518-540; Craik, Govoni, Naveh-Benjamin, & Anderson, 1996, Journal of Experimental Psychology: General, 125, 159-180). Experiment 1 confirmed the relatively small effects of DA on retrieval and also showed that retrieval operations do consume processing resources. The experiment also found that the effect is not attributable to a trade-off in performance with the concurrent task or to recognition decisions made on the basis of familiarity judgments. Participants made levels-of-processing (LOP) judgments during encoding to check whether deeper semantic judgments were differentially vulnerable to the effects of DA. In fact DA did not interact with LOP. Experiment 2 explored reports that the comparatively slight effect of DA on recognition accuracy is accompanied by a compensatory increase in recognition latency (Baddeley et al., 1984). The experiment replicated findings that neither DA nor differential emphasis between recognition and a concurrent continuous reaction time (CRT) task affected recognition accuracy, but also found evidence for a lawful trade-off in decision latencies between recognition and CRT performance. Further analysis showed that the relationship between response rates on the two tasks was well described by a linear function, and that this function was demonstrated by the majority of individual participants. It is concluded that the small effect of DA on recognition performance is attributable to a trade-off within the recognition task itself; accuracy is maintained by a compensatory increase in decision latency.

Cognitive Contributors to Multiple Errands Test (MET) Performance.

OBJECTIVE: The Multiple Errands Test (MET) was designed to measure the effect of executive dysfunction on everyday life activities, but little is known about the cognitive requirements for successful performance. This study's objective was to investigate cognitive functions associated with successful MET performance, specifically, the Baycrest-MET. METHOD: Correlation analysis examined relationships between Baycrest-MET performance and neuropsychological functioning in participants with acquired brain injury (ABI; N = 27). RESULTS: The association of tasks omitted with executive function (EF) accounted for 15.2%-42.3% of the variance; the association of tasks omitted with attention and processing speed, for 16.8%-24.0%; and the association of tasks omitted and total rule breaks with visuospatial memory, for 18.5%-31.4%. CONCLUSION: Poor performance on the Baycrest-MET in people with ABI is associated with impairments of EF, attention, memory, and processing speed. Different patterns of performance may arise from different constellations of impairments.

Cognitive and psychosocial function in retired professional hockey players.

BACKGROUND AND OBJECTIVE: The relationship between repeated concussions and neurodegenerative disease has received significant attention, particularly research in postmortem samples. Our objective was to characterise retired professional ice hockey players' cognitive and psychosocial functioning in relation to concussion exposure and apolipoprotein ε4 status. METHODS: Alumni athletes (N=33, aged 34-71 years) and an age-matched sample of comparison participants (N=18) were administered measures of cognitive function and questionnaires concerning psychosocial and psychiatric functioning. RESULTS: No significant group differences were found on neuropsychological measures of speeded attention, verbal memory or visuospatial functions, nor were significant differences observed on computerised measures of response speed, inhibitory control and visuospatial problem solving. Reliable group differences in cognitive performance were observed on tests of executive and intellectual function; performance on these measures was associated with concussion exposure. Group differences were observed for cognitive, affective and behavioural impairment on psychosocial questionnaires and psychiatric diagnoses. There was no evidence of differential effects associated with age in the alumni athletes. Possession of an apolipoprotein ε4 allele was associated with increased endorsement of psychiatric complaints, but not with objective cognitive performance. CONCLUSIONS: We found only subtle objective cognitive impairment in alumni athletes in the context of high subjective complaints and psychiatric impairment. Apolipoprotein ε4 status related to psychiatric, but not cognitive status. These findings provide benchmarks for the degree of cognitive and behavioural impairment in retired professional athletes and a point of comparison for future neuroimaging and longitudinal studies.

A prospective 2-site parallel intervention trial of a research-based film to increase exercise amongst older hemodialysis patients.

BACKGROUND: Evidence suggests that exercise training for hemodialysis patients positively improves morbidity and mortality outcomes, yet exercise programs remain rare and are not systematically incorporated into care. We developed a research-based film, Fit for Dialysis, designed to introduce, motivate, and sustain exercise for wellness amongst older hemodialysis patients, and exercise counseling and support by nephrologists, nurses, and family caregivers. The objective of this clinical trial is to determine whether and in what ways Fit for Dialysis improves outcomes and influences knowledge/attitudes regarding the importance of exercise for wellness in the context of end-stage renal disease. METHODS/DESIGN: This 2-site parallel intervention trial will recruit 60 older hemodialysis patients from two urban hospitals. The trial will compare the film + a 16-week exercise program in one hospital, with a 16-week exercise-only program in another hospital. Physical fitness and activity measures will be performed at baseline, 8 and 16 weeks, and 12 weeks after the end of the program. These include the 2-min Walk Test, Grip Strength, Duke Activity Status Index, and the Timed Up-and-Go Test, as well as wearing a pedometer for one week. Throughout the 16-week exercise program, and at 12 weeks after, we will record patients' exercise using the Godin Leisure-time Exercise Questionnaire. Patients will also keep a diary of the exercise that they do at home on non-dialysis days. Qualitative interviews, conducted at baseline, 8, and 16 weeks, will explore the impact of Fit for Dialysis on the knowledge/attitudes of patients, family caregivers, and nephrology staff regarding exercise for wellness, and in what ways the film is effective in educating, motivating, or sustaining patient exercise during dialysis, at home, and in the community. DISCUSSION: This research will determine for whom Fit for Dialysis is effective, why, and under what conditions. If Fit for Dialysis is proven beneficial to patients, nephrology staff and family caregivers, research-based film as a model to support exercise promotion and adherence could be used to support the National Kidney Foundation's guideline recommendation (NKF-KDOQI) that exercise be incorporated into the care and treatment of dialysis patients. TRIAL REGISTRATION: NCT02754271 (ClinicalTrials.gov), retroactively registered on April 21, 2016.