Mike Allerhand

Sedentary Behavior in the First Year After Stroke: A Longitudinal Cohort Study With Objective Measures

OBJECTIVEnTo 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.nnnDESIGNnLongitudinal cohort study of patients with acute stroke who were followed over 1 year.nnnSETTINGnAcute teaching hospital or outpatient clinic, and the community after discharge.nnnPARTICIPANTSnA 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.nnnINTERVENTIONSnNot applicable.nnnMAIN OUTCOME MEASURESnObjective measures of amount and pattern of time spent in sedentary behavior: total sedentary time, weighted median sedentary bout length, and fragmentation index.nnnRESULTSnStroke 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).xa0Higher stroke severity and less functional independence were associated cross-sectionally with more sedentary behavior (β=.11, SE=.05, P=.020 and β=-.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.nnnCONCLUSIONSnStroke 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.

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 Alzheimers 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.

Age-related Changes in Memory and Fluid Reasoning in a Sample of Healthy Old People

ABSTRACT Participants in the Healthy Old People in Edinburgh (HOPE) study (N = 398) were assessed on Ravens Progressive Matrices and Logical Memory on up to three occasions. Covariates included education, social class, disease and medication status, blood pressure and study outcome. Ravens 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 Ravens. 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.

Do white matter hyperintensities mediate the association between brain iron deposition and cognitive abilities in older people

Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined.

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.

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 (nu2009=u2009662) of individuals with a mean age of 73xa0years. 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, 72.8xa0% 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 ru2009=u2009−0.165), but no relation to intelligence in childhood (ru2009=u20090.043, pu2009=u20090.282). 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.

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.

Longitudinal serum S100β and brain ageing in the Lothian Birth Cohort 1936

Elevated serum and cerebrospinal fluid concentrations of S100β, 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 S100β 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 S100β 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 S100β 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 S100β after false discovery rate correction. These data provide some weak evidence that S100β may be an informative biomarker of brain white matter aging.

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 (Ns = 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.