Lateral thinking: Neurodegeneration of the cortical cholinergic system in Alzheimer's disease.

INTRODUCTION: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. METHODS: 187 participants were included in this study who were either healthy controls (HC; n = 50) or had early mild cognitive impairment (EMCI; n = 50), late MCI (LMCI; n = 37), or AD (n = 50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. RESULTS: NBM volume was smallest in AD followed by LMCI (p < 0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p < 0.001). Both MCI groups had higher lateral tract MD compared to HC (p < 0.05). Medial tract MD was higher in LMCI (p = 0.008), but not EMCI (p = 0.09) compared to HC. Higher lateral tract MD was associated with executive function (p = 0.001) and language (p = 0.02). DISCUSSION: Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.

Lateral Thinking: Pathway Specific Neurodegeneration of the Cortical Cholinergic System in Alzheimer's Disease.

INTRODUCTION: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. METHODS: 187 participants were included in this study who were either healthy controls (HC; n=50) or had early mild cognitive impairment (EMCI; n=50), late MCI (LMCI; n=37), or AD (n=50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. RESULTS: NBM volume was smallest in AD followed by LMCI (p<0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p<0.001). Both MCI groups had higher lateral tract MD compared to HC (p<0.05). Medial tract MD was higher in LMCI (p=0.008), but not EMCI (p=0.09) compared to HC. Higher lateral tract MD was associated with executive function (p=0.001) and language (p=0.02). DISCUSSION: Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.

An Individualized Tractography Pipeline for the Nucleus Basalis of Meynert Lateral Tract.

Background: At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in PD. Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM. Methods: Using structural and diffusion weighted imaging, we developed a tractography pipeline for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual pipeline is more reliable than an existing automated pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients. Results: The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p<0.001) and the reconstruction of the target lateral tract (p=0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p=0.25), which showed high inter- (mean Dice coefficient >0.6) and intra-rater (mean Dice coefficient >0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts. Conclusion: We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical grade imaging of healthy young adult and PD patient scans.

No laughing white matter: Reduced integrity of the cortical cholinergic pathways in Parkinson's disease-related cognitive impairment.

BACKGROUND: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory. However, research is needed to determine which pathway, if any, are associated with PD-related cognitive decline. METHODS: Thirty-seven PD patients with no mild cognitive impairment (MCI) were included in this study. Participants either developed MCI at 1-year follow up (PD MCI-Converters; n = 16) or did not (PD no-MCI; n = 21). Mean diffusivity (MD) and fractional anisotropy (FA) of the medial and lateral NBM tracts were extracted using probabilistic tractography. Between-group differences in MD and FA for each tract was compared using ANCOVA, controlling for age, sex, and disease duration. Control comparisons of the internal capsule MD and FA were also performed. Associations between baseline MD or FA and cognitive outcomes (working memory, psychomotor speed, delayed recall, and visuospatial function) were assessed using linear mixed models. RESULTS: PD MCI-Converters had significantly greater MD and lower FA (p < .001) of both NBM tracts compared to PD no-MCI. No difference was found in the MD (p = .06) or FA (p = .31) of the control region. Trends were identified between: 1) lateral tract MD and FA with working memory decline; and 2) medial tract MD and reduced psychomotor speed. CONCLUSIONS: Reduced integrity of the NBM tracts is evident in PD patients up to one year prior to the development of MCI. Thus, deterioration of the NBM tracts in PD may be an early marker of those at risk of cognitive decline.

Resistance Training Maintains White Matter and Physical Function in Older Women with Cerebral Small Vessel Disease: An Exploratory Analysis of a Randomized Controlled Trial.

Background: As the aging population grows, there is an increasing need to develop accessible interventions against risk factors for cognitive impairment and dementia, such as cerebral small vessel disease (CSVD). The progression of white matter hyperintensities (WMHs), a key hallmark of CSVD, can be slowed by resistance training (RT). We hypothesize RT preserves white matter integrity and that this preservation is associated with improved cognitive and physical function. Objective: To determine if RT preserves regional white matter integrity and if any changes are associated with cognitive and physical outcomes. Methods: Using magnetic resonance imaging data from a 12-month randomized controlled trial, we compared the effects of a twice-weekly 60-minute RT intervention versus active control on T1-weighted over T2-weighted ratio (T1w/T2w; a non-invasive proxy measure of white matter integrity) in a subset of study participants (N = 21 females, mean age = 69.7 years). We also examined the association between changes in T1w/T2w with two key outcomes of the parent study: (1) selective attention and conflict resolution, and (2) peak muscle power. Results: Compared with an active control group, RT increased T1w/T2w in the external capsule (p = 0.024) and posterior thalamic radiations (p = 0.013) to a greater degree. Increased T1w/T2w in the external capsule was associated with an increase in peak muscle power (p = 0.043) in the RT group. Conclusion: By maintaining white matter integrity, RT may be a promising intervention to counteract the pathological changes that accompany CSVD, while improving functional outcomes such as muscle power.

No Laughing White Matter: Cortical Cholinergic Pathways and Cognitive Decline in Parkinson's Disease.

Background: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory. However, research is needed to determine which pathway, if any, are associated with PD-related cognitive decline. Methods: Thirty-seven PD patients with no mild cognitive impairment (MCI) were included in this study. Participants either developed MCI at 1-year follow up (PD MCI-Converters; n=16) or did not (PD no-MCI; n=21). Mean diffusivity (MD) of the medial and lateral NBM tracts were extracted using probabilistic tractography. Between-group differences in MD for each tract was compared using ANCOVA, controlling for age, sex, and disease duration. Control comparisons of the internal capsule MD were also performed. Associations between baseline MD and cognitive outcomes (working memory, psychomotor speed, delayed recall, and visuospatial function) were assessed using linear mixed models. Results: PD MCI-Converters had significantly greater MD of both NBM tracts compared to PD no-MCI (p<.001). No difference was found in the control region (p=.06). Trends were identified between: 1) lateral tract MD, poorer visuospatial performance (p=.05) and working memory decline (p=.04); and 2) medial tract MD and reduced psychomotor speed (p=.03). Conclusions: Reduced integrity of the NBM tracts is evident in PD patients up to one year prior to the development of MCI. Thus, deterioration of the NBM tracts in PD may be an early marker of those at risk of cognitive decline.

Weight for It: Resistance Training Mitigates White Matter Hyperintensity-Related Disruption to Functional Networks in Older Females.

BACKGROUND: White matter hyperintensities (WMH) are associated with impaired cognition and increased falls risk. Resistance training (RT) is a promising intervention to reduce WMH progression, improve executive functions, and reduce falls. However, the underlying neurobiological process by which RT improves executive functions and falls risk remain unclear. We hypothesized that: 1) RT reduces the level of WMH-related disruption to functional networks; and 2) reduced disruption to the sensorimotor and attention networks will be associated with improved executive function and reduced falls risk. OBJECTIVE: Investigate the impact of 52 weeks of RT on WMH-related disruption to functional networks. METHODS: Thirty-two older females (65-75 years) were included in this exploratory analysis of a 52-week randomized controlled trial. Participants received either twice-weekly RT or balance and tone training (control). We used lesion network mapping to assess changes in WMH-related disruption to the sensorimotor, dorsal attention, and ventral attention networks. Executive function was measured using the Stroop Colour-Word Test. Falls risk was assessed using the Physiological Profile Assessment (PPA) and the foam sway test. RESULTS: RT significantly reduced the level of WMH-related disruption to the sensorimotor network (p = 0.012). Reduced disruption to the dorsal attention network was associated with improvements in Stroop performance (r = 0.527, p = 0.030). Reduced disruption to the ventral attention network was associated with reduced PPA score (r = 0.485, p = 0.049)Conclusion:RT may be a promising intervention to mitigate WMH-related disruption to the sensorimotor network. Additionally, reducing disruption to the dorsal and ventral attention networks may contribute to improved executive function and reduced falls risk respectively.

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function.

BACKGROUND: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. METHODS: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). DISCUSSION: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Alcohol Packaging As a Promotional Tool: A Focus Group Study With Young Adult Drinkers in Scotland.

OBJECTIVE: Little research has been conducted on consumer perceptions of alcohol packaging as a marketing tool. The aim of this study was to explore how young adults view and engage with alcohol packaging. METHOD: Eight focus groups were conducted in Glasgow (Scotland) with current drinkers (n = 50), segmented by age (18-24, 25-35), gender (female, male), and social grade (ABC1, C2DE). Participants were shown, allowed to handle, and asked about a range of alcoholic products. RESULTS: Five main themes emerged from the data. The first was the ubiquity of alcohol packaging, with frequent exposure reported in different settings, such as shops and drinking venues, and via marketing. The second was appeal, with pack graphics (e.g., color), structure (e.g., shape, size), and promotions (e.g., gifts, limited editions) allowing alcohol packs to catch attention, enabling products to stand out on shelves, and helping to create product and brand liking, interest, and choice. Third, alcohol packaging was frequently associated with specific occasions and activities. Fourth, alcohol packaging informed perceptions of product-consumer targeting, suitability, and intended drinker profiles. Fifth, alcohol packaging also engaged nonvisual senses (e.g., touch, sound, smell), guiding expectations of product taste and palatability. CONCLUSIONS: For young adult drinkers in Scotland, alcohol packaging can capture attention, create appeal, and help shape perceptions of the product, drinker, and drinking experience.

The role of alcohol packaging as a health communications tool: An online cross-sectional survey and experiment with young adult drinkers in the United Kingdom.

INTRODUCTION: Alcohol packaging is a potentially valuable means of communicating product and health-related information, with growing academic and political interest in its role as a health communications vehicle. METHODS: An online cross-sectional survey and experiment were conducted with a non-probability sample of 18-35-year-old drinkers in the United Kingdom (n = 1360). The survey assessed exposure to, and engagement with, current messaging on packs, and support for displaying product and health-related information. For the randomised experiment, participants were shown, and asked questions about, a vodka bottle with either no warnings (control), small text warnings, large text warnings or pictorial (image-and-text) warnings; the main binary outcome measures were negative product appeal and social acceptability, and positive cognitive and behavioural impact. RESULTS: Two-fifths of the sample rarely or never saw on-pack health-related information, with almost three-quarters rarely or never reading or looking closely at this. There was strong support for displaying a range of product and health-related information (e.g. units, ingredients) on packs. Relative to the control, products with warnings were more likely to be perceived as unappealing and socially unacceptable, and to positively impact alcohol-related cognitions and behaviours. For example, pictorial warnings were 10 times as likely to positively influence cognitions and behaviours (AOR = 10.01, 95% CI: 8.09, 17.46). DISCUSSION AND CONCLUSIONS: Alcohol packaging could have an important role in delivering health messaging. Large pictorial or text warnings may help counteract the appeal and social acceptability of alcohol products and increase awareness of risks, potentially supporting a reduction in consumption and related harms.

Mind the gaps: functional networks disrupted by white matter hyperintensities are associated with greater falls risk.

White matter hyperintensities (WMH) are associated with greater falls risk and slow gait speed. Whether these deficits are caused by the disruption of large-scale functional networks remains inconclusive. Further, physical activity moderates the association between WMHs and falls, but whether this extends to the disruption of functional networks remains unknown. One hundred and sixty-four adults (>55 years old) were included in this study. Using lesion network mapping, we identified significant correlations between the percentage of WMH-related disruption of the dorsal attention network and Physiological Profile Assessment (PPA) score (r = 0.24, p < 0.01); and between disruption of both the sensorimotor (r = 0.23, p < 0.01) and ventral attention networks (r = 0.21, p = 0.01) with foam sway. There were no significant associations with floor sway or gait speed. Physical activity moderated the association between the dorsal attention network and PPA score (p = 0.045). Thus, future research should investigate whether physical activity should be recommended in the clinical management of older adults with cerebral small vessel disease.

Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults.

Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk. Methods: Seventy-six community-dwelling older adults aged 70-80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models. Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (ß = -0.26 ± 0.11; p = 0.022) and WMH volume (ß = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (ß = -0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk. Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA.

Intensity Matters for Musculoskeletal Health: A Cross-Sectional Study on Movement Behaviors of Older Adults from High-Income Scottish and Low-Income South African Communities.

This study aimed to investigate differences in physical activity (PA) patterns and the associations between objectively measured 24-h movement behaviors and musculoskeletal measures (muscle strength, muscle mass, physical performance, and bone mineral density) in a high-income and a low-income community. This cross-sectional study recruited independent living older adults aged 60-85 years from high-income Scottish (n = 150) and low-income South African (n = 138) settings. Participants completed demographic and health questionnaires, and testing included body composition and bone mineral density (dual energy X-ray absorptiometry), physical performance (grip strength, gait speed), and PA (accelerometry). Participants accumulated similar amounts of weekly total PA, however, the Scottish cohort engaged in more moderate-to-vigorous intensity PA (MVPA) and sedentary behavior (SB), while the South African cohort spent more time sleeping and in light intensity PA (LPA). From compositional data analysis, more time spent in MVPA relative to the other movement behaviors was positively associated with higher muscle mass (p < 0.001) and strength (p = 0.001) in the Scottish cohort. Conversely, more time spent in MVPA was associated with faster gait speed (p < 0.001) and greater hip bone mineral density (p = 0.011) in the South African cohort. Our findings confirm the beneficial role of MVPA in both high- and low-income cohorts, however, the relationship MVPA had with components of musculoskeletal health in older adults differed between settings.

Painting by lesions: White matter hyperintensities disrupt functional networks and global cognition.

White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p<.001) and ventral attention network (p <. 001) was significantly correlated with MoCA score. Thus, the greater the disruption to the sensorimotor and ventral attention networks, the poorer the global cognition. Our results reveal that the visual, ventral attention, and frontoparietal networks are most vulnerable to disruptions stemming from WMHs. Additionally, we identified that disruption to the sensorimotor and ventral attention networks, as a result of WMHs, may underlie deficits in global cognition in older adults with cerebral small vessel disease.

Reshaping the path of vascular cognitive impairment with resistance training: a study protocol for a randomized controlled trial.

BACKGROUND: Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its modifiable risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities (WMHs), research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, the primary aim of this proof-of-concept randomized controlled trial is to investigate the efficacy of a 12-month, twice-weekly progressive resistance training program on cognitive function and WMH progression in adults with SIVCI. We will also assess the efficiency of the intervention. METHODS: Eighty-eight community-dwelling adults, aged > 55 years, with SIVCI from metropolitan Vancouver will be recruited to participate in this study. SIVCI will be determined by the presence of cognitive impairment (Montreal Cognitive Assessment < 26) and cerebral small vessel disease using computed tomography or magnetic resonance imaging. Participants will be randomly allocated to a twice-weekly exercise program of (1) progressive resistance training or (2) balance and tone training (i.e., active control). The primary outcomes are cognitive function measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-13 with additional cognitive tests) and WMH progression. DISCUSSION: The burden of SIVCI is immense, and to our knowledge, this will be the first study to quantify the effect of progressive resistance training on cognitive function and WMH progression among adults with SIVCI. Slowing the rate of cognitive decline and WMH progression could preserve functional independence and quality of life. This could lead to reduced health care costs and avoidance of early institutional care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02669394 . Registered on February 1, 2016.

Shining the Light on the MotionWatch8 Light Sensor for Sleep and Aging Research: What Can We Measure and What Are We Missing?

BACKGROUND: Poor sleep is common among older adults at risk for dementia and may be due to circadian dysregulation. Light is the most important external stimulus to the circadian clock and bright light therapy (BLT) has been used for >20 years to help realign circadian rhythms. However, the ability of field methods (e.g., actigraphy) to accurately determine the type and intensity of light is unknown. OBJECTIVE: We examined the ability of the MotionWatch8 (MW8) light sensor to determine: 1) light versus dark, 2) electrical light versus daylight, and 3) device-based BLT versus light which was not BLT. METHODS: We tested the MW8 under 17 daily light scenarios. Light exposure data was collected for 5 minutes during each scenario. Concurrently, we measured light exposure using the LT40 Light Meter, a sensitive measure of light intensity. We then developed individual cut-points using receiver operator characteristics analyses to determine optimal MW8 cut-points for 1) light versus dark; 2) electrical light versus daylight; and 3) light from a BLT box versus light which was not BLT. Bland-Altman plots tested the precision of the MW8 compared to the LT40. RESULTS: The MW8 accurately discriminated light versus dark (>32 lux), and electrical light versus daylight (<323 lux). However, the MW8 had poor accuracy for 1) discriminating BLT from light which was not BLT; and 2) low precision compared to the LT40. CONCLUSION: The MW8 appears to be able to discern light versus dark and electrical light versus daylight; however, there remains a need for accurate field methods capable of measuring light exposure.

Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease.

BACKGROUND: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. OBJECTIVE: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. METHODS: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. RESULTS: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (ß â€Š= -0.29, p = 0.037) and poorer working memory (ß= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132). CONCLUSION: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

Functional connectivity underpinning changes in life-space mobility in older adults with mild cognitive impairment: A 12-month prospective study.

Subtle changes in mobility exist among older adults with mild cognitive impairment (MCI). Life-space mobility defines the frequency and extent of movements in the environment, and lower life-space mobility is associated with adverse health outcomes and MCI. Currently, the underlying mechanism of this association is not well understood. This study examined the functional neural correlates of life-space mobility in community-dwelling older adults with MCI. We first conducted a cross-sectional investigation of the association between resting-state default mode network (DMN) and sensori-motor network (SMN) connectivity and life-space mobility (assessed by the Life-Space Assessment (LSA)) among 60 community-dwelling older adults with MCI using aggregated data from two studies - baseline data from a randomized controlled trial (n = 20) and baseline data from a 12-month prospective study (n = 40). Using data from the 12-month prospective study (n = 35), we then examined whether baseline internetwork connectivity predicts reduced life-space mobility over 12 months. The cross-sectional analysis showed higher DMN-SMN connectivity was associated with lower LSA scores after adjusting for baseline global cognitive function and baseline age (p < 0.01). A significant reduction in LSA scores was observed in the 35 participants of the 12-month prospective study (paired sample t-test mean change = -6.53, p = 0.01). Greater baseline DMN-SMN connectivity was associated with greater reduction in life-space mobility at 12 months (p = 0.04) after adjusting for baseline age, global cognitive function, and LSA score. Our findings suggest that lower and reduced life-space mobility in older adults with MCI may be due to altered functional architecture of the brain such that normal neuro-cognitive motor behaviours may be disrupted.

Registered nurses' perceptions and experiences of autonomy: a descriptive phenomenological study.

BACKGROUND: Professional autonomy is a key concept in understanding nurses' roles in delivering patient care. Recent research exploring the role of autonomy in the nursing work environment indicated that English and American nurses had differing perceptions of autonomy. This qualitative study aimed to explore the understanding and experiences of autonomy of nurses working in England. METHODS: A descriptive phenomenological analysis of data from 48 semi-structured interviews with registered nurses from two National Health Service (NHS) hospitals (purposive sample) was used to explore the concept of autonomy. RESULTS: Six themes were identified: working independently; working in a team; having professional skills and knowledge; involvement in autonomy; boundaries around autonomy; and developing autonomy requires support. A key finding was that nurses related autonomy to their clinical work and to the immediate work environment of their ward, rather than to a wider professional context. Nurses also perceived that autonomy could be turned off and on rather than comprising an integrated aspect of nursing. CONCLUSIONS: Findings suggest that nurses in England, as framed by the sample, had a local ward-focused view of autonomy in comparison to nurses in America, who were reported to relate autonomy to a wider involvement in hospital level committees. Findings further indicate that autonomy was practiced occasionally, rather than incorporated into practice. Findings highlight the need for nurses in England to adopt a broader perspective and actively contribute to writing hospital guidelines and policies that recognise the importance of autonomy to nurse training and practice.

The nursing work environment and quality of care: Content analysis of comments made by registered nurses responding to the Essentials of Magnetism II scale.

AIM: To report a qualitative study of themes Registered Nurses raised spontaneously about their work environment, in a cross-sectional survey study when responding to the Essentials of Magnetism II (EOMII) scale. DESIGN: Qualitative descriptive survey. METHODS: At the end of the EOMII scale, a free form text section was included asking nurses to add comments about their ward/work environment. Of the 247 nurses who completed the EOMII scale, 30% (N = 75) provided comments. Inductive content analysis was used to analyse the textual information generated. RESULTS: Three key themes emerged: "nurses need nurses to nurse"; working as a team and workplace environment. Participants described issues they were facing which comprised high turnover rates, inadequate staffing levels, increasing workload and high stress levels. Particular attention was drawn to the role of the ward manager in promoting a positive work environment, good teamwork and quality patient care.