Search

In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline. • We identified two morphometric brain signatures of cognitive resilience • Larger anterior and medial temporal volumes were associated with higher resilience • Larger ventricles were associated with lower resilience • Six previously identified cortical resilience proteins were linked to the volumes • RPH3A and CPLX1 were related to smaller ventricles beyond neuropathological burden. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that dividing attention would strengthen the ability to detect mild cognitive impairment (MCI) and specific cognitive abilities from Timed Up and Go (TUG) performance in the community setting. While wearing a belt-worn sensor, 757 dementia-free older adults completed TUG during two conditions, with and without a concurrent verbal serial subtraction task. We segmented TUG into its four subtasks (i.e., walking, turning, and two postural transitions), and extracted 18 measures that were summarized into nine validated sensor metrics. Participants also underwent a detailed cognitive assessment during the same visit. We then employed a series of regression models to determine the combinations of subtask sensor metrics most strongly associated with MCI and specific cognitive abilities for each condition. We also compared subtask performances with and without dividing attention to determine whether the costs of divided attention were associated with cognition. While slower TUG walking and turning were associated with higher odds of MCI under normal conditions, these and other subtask associations became more strongly linked to MCI when TUG was performed under divided attention. Walking and turns were also most strongly associated with executive function and attention, particularly under divided attention. These differential associations with cognition were mirrored by performance costs. However, since several TUG subtasks were more strongly associated with MCI and cognitive abilities when performed under divided attention, future work is needed to determine how instrumented dual-task TUG testing can more accurately estimate risk for late-life cognitive impairment in older adults. [ABSTRACT FROM AUTHOR]

• Metabolic syndrome is the clustering of 3 or more cardiovascular risk factors. • Connectivity between core brain networks and rest of the brain voxels were evaluated. • Metabolic syndrome group showed hyperconnectivity and loss of modularity across brain networks. • Most of the core networks showed higher between-network metabolic syndrome -related associations. The objective of this study is to examine whether metabolic syndrome (MetS), the clustering of 3 or more cardiovascular risk factors, disrupts the resting-state functional connectivity (FC) of the large-scale cortical brain networks. Resting-state functional magnetic resonance imaging data were collected from seventy-eight middle-aged and older adults living with and without MetS (27 MetS; 51 non-MetS). FC maps were derived from the time series of intrinsic activity in the large-scale brain networks by correlating the spatially averaged time series with all brain voxels using a whole-brain seed-based FC approach. Participants with MetS showed hyperconnectivity across the core brain regions with evidence of loss of modularity when compared with non-MetS individuals. Furthermore, patterns of higher between-network MetS-related effects were observed across most of the seed regions in both right and left hemispheres. These findings indicate that MetS is associated with altered intrinsic communication across core neural networks and disrupted between-network connections across the brain due to the co-occurring vascular risk factors in MetS. [ABSTRACT FROM AUTHOR]

Background: In older adults, compromised white matter tract integrity within the brain has been linked to impairments in mobility. We contend that poorer integrity disrupts mobility by altering the processing of sensorimotor and cognitive and attentional resources in neural networks. The richness of information processing in a given network can be quantified by calculating the complexity of resting-state functional MRI time series. We hypothesized that (i) older adults with lower brain complexity, specifically within sensorimotor, executive, and attention networks, would exhibit slower walking speed and greater dual-task costs (ie, dual-task cost) and (ii) such complexity would mediate the effect of white matter integrity on these metrics of mobility.Methods: Fifty-three older adults completed a walking assessment and a neuroimaging protocol. Brain complexity was quantified by calculating the multiscale entropy of the resting-state functional MRI signal within seven previously defined functional networks. The white matter integrity across structures of the corpus callosum was quantified using fractional anisotropy.Results: Participants with lower resting-state complexity within the sensorimotor, executive, and attention networks walked more slowly under single- and dual-task (ie, walking while performing a serial-subtraction task) conditions (β > 0.28, p ≤ .01) and had a greater dual-task cost (β < -0.28, p < .04). Complexity in these networks mediated the influence of the corpus callosum genu on both single- (indirect effects > 0.15, 95% confidence intervals = 0.02-0.32) and dual-task walking speeds (indirect effects > 0.13, 95% confidence intervals = 0.02-0.33).Conclusion: These results suggest that the multiscale dynamics of resting-state brain activity correlate with mobility and mediate the effect of the microstructural integrity in the corpus callosum genu on walking speed in older adults. [ABSTRACT FROM AUTHOR]

Background: Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced task-related ΔCBF is associated with reduced neural activity in specific brain regions, as measured by blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI).Methods: We assessed the regional changes in neural activity associated with reduced middle cerebral artery (MCA) task-related ΔCBF to an executive task and slow walking speed in 67 community-dwelling older adults from the MOBILIZE Boston Study. Participants underwent walking assessments and TCD ultrasonography measures of MCA ΔCBF during the n-back task of executive function. A subset of participants (n = 27) completed the same task during fMRI. Individual BOLD activation maps for the n-back task were correlated with TCD measures and network-level averages were associated with TCD and preferred walking speed.Results: Participants with diminished task-related ΔCBF walked more slowly (β = .39, p = .001). fMRI revealed significant associations between task-related ΔCBF and regional BOLD activation in several brain regions/networks supplied by the MCA. Of these regions and networks, those within the executive network were most strongly associated with walking speed (β = .36, p = .01).Conclusions: Task-related ΔCBF during an executive function task is related to activation in several neural networks and impairment in the ability to recruit the executive network in particular is associated with slow walking speed in older adults. [ABSTRACT FROM AUTHOR]

Distractor suppression, the ability to filter and ignore task-irrelevant information, is critical for efficient task performance. While successful distractor suppression relies on a balance of activity in neural networks responsible for attention maintenance (dorsal attention network; DAN), reorientation (ventral attention network; VAN), and internal thought (default mode network, DMN), the degree to which intrinsic connectivity within and between these networks contributes to individual differences in distractor suppression ability is not well-characterized. For the purposes of understanding these interactions, the current study collected resting-state fMRI data from 32 Veterans and, several months later (7±5 months apart), performance on the additional singleton paradigm, a measure of distractor suppression. Using multivariate support vector regression models composed of resting state connectivity between regions of the DAN, VAN, and DMN, and a leave-one-subject-out cross-validation procedure, we were able to predict an individual's task performance, yielding a significant correlation between the actual and predicted distractor suppression (r=0.48, p =0.0053). Network-level analyses revealed that greater within-network DMN connectivity was predictive of better distractor suppression, while greater connectivity between the DMN and attention networks was predictive of poorer distractor suppression. The strongest connection hubs were determined to be the right frontal eye field and temporoparietal junction of the DAN and VAN, respectively, and medial (ventromedial prefrontal and posterior cingulate cortices) and bilateral prefrontal regions of the DMN. These results are amongst a small but growing number of studies demonstrating that resting state connectivity is related to stable individual differences in cognitive ability, and suggest that greater integrity and independence of the DMN is related to better attentional ability. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy and helmet telemetry were used to monitor the neural metabolic response to repetitive head collisions in 25 high school American football athletes. Specific hit characteristics were determined highly predictive of metabolic alterations, suggesting that sub-concussive blows can produce biochemical changes and potentially lead to neurological problems. [ABSTRACT FROM PUBLISHER]

With growing evidence of long-term neurological damage in individuals enduring repetitive head trauma, it is critical to detect lower-level damage accumulation for the early diagnosis of injury in at-risk populations. Proton magnetic resonance spectroscopic scans of the dorsolateral prefrontal cortex and primary motor cortex were collected from high school American (gridiron) football athletes, prior to and during their competition seasons. Although no concussions were diagnosed, significant metabolic deviations from baseline and non-collision sport controls were revealed. Overall the findings indicate underlying biochemical changes, consequential to repetitive hits, which have previously gone unnoticed due to a lack of traditional neurological symptoms. [ABSTRACT FROM PUBLISHER]

Abstract: Prior research has linked visual perception of tools with plausible motor strategies. Thus, observing a tool activates the putative action-stream, including the left posterior parietal cortex. Observing a hand functionally grasping a tool involves the inferior frontal cortex. However, tool-use movements are performed in a contextual and grasp specific manner, rather than relative isolation. Our prior behavioral data has demonstrated that the context of tool-use (by pairing the tool with different objects) and varying hand grasp postures of the tool can interact to modulate subjects'' reaction times while evaluating tool-object content. Specifically, perceptual judgment was delayed in the evaluation of functional tool-object pairings (Correct context) when the tool was non-functionally (Manipulative) grasped. Here, we hypothesized that this behavioral interference seen with the Manipulative posture would be due to increased and extended left parietofrontal activity possibly underlying motor simulations when resolving action conflict due to this particular grasp at time scales relevant to the behavioral data. Further, we hypothesized that this neural effect will be restricted to the Correct tool-object context wherein action affordances are at a maximum. 64-channel electroencephalography (EEG) was recorded from 16 right-handed subjects while viewing images depicting three classes of tool–object contexts: functionally Correct (e.g. coffee pot–coffee mug), functionally Incorrect (e.g. coffee pot–marker) and Spatial (coffee pot–milk). The Spatial context pairs a tool and object that would not functionally match, but may commonly appear in the same scene. These three contexts were modified by hand interaction: No Hand, Static Hand near the tool, Functional Hand posture and Manipulative Hand posture. The Manipulative posture is convenient for relocating a tool but does not afford a functional engagement of the tool on the target object. Subjects were instructed to visually assess whether the pictures displayed correct tool-object associations. EEG data was analyzed in time–voltage and time–frequency domains. Overall, Static Hand, Functional and Manipulative postures cause early activation (100–400ms post image onset) of parietofrontal areas, to varying intensity in each context, when compared to the No Hand control condition. However, when context is Correct, only the Manipulative Posture significantly induces extended neural responses, predominantly over right parietal and right frontal areas [400–600ms post image onset]. Significant power increase was observed in the theta band [4–8Hz] over the right frontal area, [0–500ms]. In addition, when context is Spatial, Manipulative posture alone significantly induces extended neural responses, over bilateral parietofrontal and left motor areas [400–600ms]. Significant power decrease occurred primarily in beta bands [12–16, 20–25Hz] over the aforementioned brain areas [400–600ms]. Here, we demonstrate that the neural processing of tool-object perception is sensitive to several factors. While both Functional and Manipulative postures in Correct context engage predominantly an early left parietofrontal circuit, the Manipulative posture alone extends the neural response and transitions to a late right parietofrontal network. This suggests engagement of a right neural system to evaluate action affordances when hand posture does not support action (Manipulative). Additionally, when tool-use context is ambiguous (Spatial context), there is increased bilateral parietofrontal activation and, extended neural response for the Manipulative posture. These results point to the existence of other networks evaluating tool-object associations when motoric affordances are not readily apparent and underlie corresponding delayed perceptual judgment in our prior behavioral data wherein Manipulative postures had exclusively interfered in judging tool-object content. [Copyright &y& Elsevier]

With growing evidence of long-term neurological damage in individuals enduring repetitive head trauma, it is critical to detect lower-level damage accumulation for the early diagnosis of injury in at-risk populations. Proton magnetic resonance spectroscopic scans of the dorsolateral prefrontal cortex and primary motor cortex were collected from high school American (gridiron) football athletes, prior to and during their competition seasons. Although no concussions were diagnosed, significant metabolic deviations from baseline and non-collision sport controls were revealed. Overall the findings indicate underlying biochemical changes, consequential to repetitive hits, which have previously gone unnoticed due to a lack of traditional neurological symptoms. [ABSTRACT FROM AUTHOR]

Objectives : Our objectives were to determine whether pregnancy intendedness changes as the pregnancy progresses and, if so, in what direction. Methods : Intendedness questions similar to those used in the 1988 National Survey of Family Growth were administered in the second trimester of pregnancy (16–18 weeks) and again in the third trimester (30–32 weeks) to a population of 1223 low-income women who were medically at high risk. Information was also collected on characteristics identified in previous studies as being associated with intendedness. Changes in reported intendedness status were categorized as positive if the woman switched from unwanted to mistimed or intended or from mistimed to intended. Changes were categorized as negative if the woman switched from intended to mistimed or unwanted or from mistimed to unwanted. Results : Among the 436 women who reported an intended pregnancy at midpregnancy, 79.1% still reported the pregnancy as intended in late pregnancy, while 15.9% moved to mistimed and 6.4% to unwanted. Of the 601 women who reported a mistimed pregnancy in midpregnancy, 80.9% still reported it as mistimed in late pregnancy, with 13.9% switching to intended and 5.2% switching to unwanted. Of the 186 women who reported an unwanted pregnancy at midpregnancy, 62.9% remained unwanted, 30.7% switched to mistimed, and 6.4% switched to intended. Conclusions : This study indicates that intendedness is not fixed during pregnancy. Between the first and the second administration of the intendedness questions, 275 (22.5%) of the women changed their responses and the larger percentage (12.5%) changed them in a positive direction. These findings have both policy and clinical implications. [ABSTRACT FROM AUTHOR]

At autopsy, African American decedents often have mixed Alzheimer's and cerebrovascular brain pathologies including arteriolosclerosis. We applied a novel in-vivo classifier of ARTerioloSclerosis (ARTS) in 167 older African Americans (∼75y of age) with > 2 biennial 3 T MRI scans and > 3 years of associated cognitive follow-up to determine if ARTS scores (higher score=higher likelihood of arteriolosclerosis) changed over time and if this change associated with changes in cognition in the same individuals. Mixed effects regression models tested whether ARTS scores increased over time, while simultaneous mixed effects regression models estimated the simultaneous rates of change in both ARTS and cognition and the correlation of these changes. ARTS scores increased over time (estimate=0.030, SE=0.002, p < 0.0001). Faster increases in ARTS were associated with faster rates of global cognitive decline (r = −0.447, p = 0.006) and domain-specific cognitive functions. Applying an in-vivo marker of arteriolosclerosis in an African American cohort revealed that the likelihood of arteriolosclerosis increases over time, and participants whose ARTS scores increased more rapidly tended to have faster than average rates of cognitive decline. • Many cerebrovascular pathologies cannot be directly measured in-vivo. • We applied a novel in-vivo classifier of ARTerioloSclerosis in African Americans. • ARTS scores increased over time. • More rapidly increasing ARTS scores associated with more rapid cognitive decline. [ABSTRACT FROM AUTHOR]

Several studies have examined how individual differences in sustained attention relate to functional brain measures (e.g., functional connectivity), but far fewer studies relate sustained attention ability, or cognition in general, to individual differences in cortical structure. Functional magnetic resonance imaging meta‐analyses and patient work have highlighted that frontoparietal regions, lateralized to the right hemisphere, are critical for sustained attention, though recent work implicates a broader expanse of brain regions. The current study sought to determine if and where variation in cortical thickness is significantly associated with sustained attention performance. Sustained attention was measured using the gradual onset continuous performance task and the Test of Variables of Attention in 125 adult Veteran participants after acquiring two high‐resolution structural MRI scans. Whole‐brain vertex‐wise analyses of the cortex demonstrated that better sustained attention was associated with increased thickness in visual, somatomotor, frontal, and parietal cortices, especially in the right hemisphere. Network‐based analyses revealed relationships between sustained attention and cortical thickness in the dorsal attention, ventral attention, somatomotor, and visual networks. These results indicate cortical thickness in multiple regions and networks is associated with sustained attention, and add to the growing knowledge of how structural MRI can help explain individual differences in cognition. [ABSTRACT FROM AUTHOR]

Presents the six cultural phenomena that must be considered when delegating to a nursing staff with a culturally diverse background in the United States. Need to be aware of communication patterns; Four distinct zones of interpersonal space; Family unit as the single most important social organization; Time orientation; Environmental control; Biological variations; Art of delegating.

Introduction Interpersonal early life trauma (I- ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning are well characterized, deficits in general cognitive functioning have also been documented. However, the neural underpinnings of cognitive dysfunction in adults with a history of I- ELT and the potential relationship between amygdala-based functional connectivity and behavioral performance are currently poorly understood. This study examined how I- ELT affects the cognitive and neural mechanisms supporting sustained attention. Methods A total of 66 Veterans (18 with and 48 without a history of I- ELT) completed a nonemotional sustained attention task during functional MRI. Results The individuals with I- ELT showed significant impairments in sustained attention (i.e., higher error rates, greater response variability). This cohort exhibited increased amygdala functional connectivity with the prefrontal cortex and decreased functional connectivity with the parahippocampal gyrus when compared to those without I- ELT. These connections were significantly correlated with individual differences in sustained attention performance. Notably, classification analyses revealed that the pattern of amygdala connectivity across the whole brain was able to classify I- ELT status with 70% accuracy. Conclusion These results provide evidence of a lasting negative impact for those with a history of I- ELT on sustained attention ability. They also highlight a critical role for amygdala functioning in cognitive control and sustained attention for those with a history of I- ELT, which may underlie the observed attention deficits in clinical assessments and cognitive tests involving both emotional and nonemotional stimuli. [ABSTRACT FROM AUTHOR]

While there has been a proliferation of neuroimaging studies on cognitive decline in older non‐Hispanic White adults, there is a dearth of knowledge regarding neuroimaging correlates of cognitive decline in Black adults. Resting‐state functional neuroimaging approaches may be particularly sensitive to early cognitive decline, but there are no studies that we know of that apply this approach to examining associations of brain function to cognition in older Black adults. We investigated the association of cognitive decline with whole‐brain voxel‐wise functional connectivity to the hippocampus, a key brain region functionally implicated in early Alzheimer's dementia, in 132 older Black adults without dementia participating in the Minority Aging Research Study and Rush Memory and Aging Project, two longitudinal studies of aging that include harmonized annual cognitive assessments and magnetic resonance imaging brain imaging. In models adjusted for demographic factors (age, education, sex), global cognitive decline was associated with functional connectivity of the hippocampus to three clusters in the right and left frontal regions of the dorsolateral prefrontal cortex. In domain‐specific analyses, decline in semantic memory was associated with functional connectivity of the hippocampus to bilateral clusters in the precentral gyrus, and decline in perceptual speed was inversely associated with connectivity of the hippocampus to the bilateral intracalcarine cortex and the right fusiform gyrus. These findings elucidate neurobiological mechanisms underlying cognitive decline in older Black adults and may point to specific targets of intervention for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Sub-concussive head impacts are identified as a source of accrued damage. Football athletes experience hundreds of such blows each season. Resting state functional magnetic resonance imaging was used to prospectively study changes in Default Mode Network connectivity for clinically asymptomatic high school football athletes. Athletes exhibited short-term changes relative to baseline and across sessions. [ABSTRACT FROM PUBLISHER]

• Identification of race-relevant biomarkers is critically needed • Examined within-Black variability in associations of DBM to cognitive decline • Less hippocampal tissue related to lower episodic memory but not decline • Less non-hippocampal, temporal & frontal tissue related to cognitive decline • Less parietal WM & splenium tissue related to cognitive level & decline respectively Blacks are at higher risk of developing cognitive impairment with age than non-Hispanic Whites, yet most brain morphometry and cognition research is performed with White samples or with mixed samples that control for race or compare across racial groups. A deeper understanding of the within-group variability in associations between brain structure and cognitive decline in Blacks is critically important for designing appropriate outcomes for clinical trials, predicting adverse outcomes, and developing interventions to preserve cognitive function, but no studies have examined these associations longitudinally within Blacks. We performed deformation-based morphometry in 376 older Black participants without dementia and examined associations of deformation-based morphometry with cognitive level and decline for global cognition and five cognitive domains. After correcting for widespread age-associated effects, there remained regions with less tissue and more cerebrospinal fluid associated with level and rate of decline in global cognition, memory, and perceptual speed. Further study is needed to examine the moderators of these associations, identify adverse outcomes predicted by brain morphometry, and deepen knowledge of underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To test whether postmortem MRI captures brain tissue characteristics that mediate the association between physical activity and cognition in older adults. Methods: Participants (N = 318) were older adults from the Rush Memory and Aging Project who wore a device to quantify physical activity and also underwent detailed cognitive and motor testing. Following death, cerebral hemispheres underwent MRI to quantify the transverse relaxation rate R2, a metric related to tissue microstructure. For analyses, we reduced the dimensionality of the R2 maps from approximately 500,000 voxels to 30 components using spatial independent component analysis (ICA). Via path analysis, we examined whether these R2 components attenuated the association between physical activity and cognition, controlling for motor abilities and indices of common brain pathologies. Results: Two of the 30 R2 components were associated with both total daily physical activity and global cognition assessed proximate to death. We visualized these components by highlighting the clusters of voxels whose R2 values contributed most strongly to each. One of these spatial signatures spanned periventricular white matter and hippocampus, while the other encompassed white matter of the occipital lobe. These two R2 components partially mediated the association between physical activity and cognition, accounting for 12.7% of the relationship (p =.01). This mediation remained evident after controlling for motor abilities and neurodegenerative and vascular brain pathologies. Conclusion: The association between physically activity and cognition in older adults is partially accounted for by MRI-based signatures of brain tissue microstructure. Further studies are needed to elucidate the molecular mechanisms underlying this pathway. [ABSTRACT FROM AUTHOR]

Human brains develop across the life span and largely vary in morphology. Adolescent collision-sport athletes undergo repetitive head impacts over years of practices and competitions, and therefore may exhibit a neuroanatomical trajectory different from healthy adolescents in general. However, an unbiased brain atlas targeting these individuals does not exist. Although standardized brain atlases facilitate spatial normalization and voxel-wise analysis at the group level, when the underlying neuroanatomy does not represent the study population, greater biases and errors can be introduced during spatial normalization, confounding subsequent voxel-wise analysis and statistical findings. In this work, targeting early-to-middle adolescent (EMA, ages 13–19) collision-sport athletes, we developed population-specific brain atlases that include templates (T1-weighted and diffusion tensor magnetic resonance imaging) and semantic labels (cortical and white matter parcellations). Compared to standardized adult or age-appropriate templates, our templates better characterized the neuroanatomy of the EMA collision-sport athletes, reduced biases introduced during spatial normalization, and exhibited higher sensitivity in diffusion tensor imaging analysis. In summary, these results suggest the population-specific brain atlases are more appropriate towards reproducible and meaningful statistical results, which better clarify mechanisms of traumatic brain injury and monitor brain health for EMA collision-sport athletes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Random effects meta-analysis is not suitable when the number of MRI scanners is small. • Pooling performs poorly when there is undue variation due to scanner differences. • The proposed approach performs better than random effects meta-analysis and pooling. Neuroimaging data from large epidemiologic cohort studies often come from multiple scanners. The variations of MRI measurements due to differences in magnetic field strength, image acquisition protocols, and scanner vendors can influence the interpretation of aggregated data. The purpose of the present study was to compare methods that meta-analyze findings from a small number of different MRI scanners. We proposed a bootstrap resampling method using individual participant data and compared it with two common random effects meta-analysis methods, DerSimonian-Laird and Hartung-Knapp, and a conventional pooling method that combines MRI data from different scanners. We first performed simulations to compare the power and coverage probabilities of the four methods in the absence and presence of scanner effects on measurements. We then examined the association of age with white matter hyperintensity (WMH) volumes from 787 participants. In simulations, the bootstrap approach performed better than the other three methods in terms of coverage probability and power when scanner differences were present. However, the bootstrap approach was consistent with pooling, the optimal approach, when scanner differences were absent. In the association of age with WMH volume, we observed that age was significantly associated with WMH volumes using the bootstrap approach, pooling, and the DerSimonian-Laird method, but not using the Hartung-Knapp method (p < 0.0001 for the bootstrap approach, DerSimonian-Laird, and pooling but p = 0.1439 for the Hartung-Knapp approach). The bootstrap approach using individual participant data is suitable for integrating outcomes from multiple MRI scanners regardless of absence or presence of scanner effects on measurements. [ABSTRACT FROM AUTHOR]