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Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network.

ABSTRACT: BACKGROUND/OBJECTIVES:Memory clinic patients commonly also have declined physical performance. This may be attributable to white matter injury, due to vascular damage or neurodegeneration. Quantifying white matter injury is made possible by new magnetic resonance imaging (MRI) techniques, including diffusion-weighted imaging (DWI) of network connectivity. We investigated whether physical performance in memory clinic patients is related to white matter network connectivity. DESIGN:Observational cross-sectional study. SETTING:Memory clinic. PARTICIPANTS:Patients referred to a memory clinic with vascular brain injury on MRI (n = 90; average age = 72?years; 60% male; 34% with diagnosis Alzheimer disease). MEASUREMENTS:We reconstructed structural brain networks from DWI with fiber tractography and used graph theory to calculate global efficiency, fractional anisotropy (FA), and mean diffusivity (MD) of the white matter, and nodal strength (mean FA or MD of all white matter tracts connected to a node). Assessment of physical performance included gait speed, chair stand time, and Short Physical Performance Battery (SPPB) score. RESULTS:Lower global efficiency, lower FA, and higher MD correlated with poorer gait speed, SPPB scores, and chair stand times (R range = 0.23-0.42). Global efficiency and FA explained 5% to 16% of the variance in gait speed, chair stand times, and SPPB scores, independent of age and sex. Moreover, global efficiency and FA explained an additional 4% to 5% of variance on top of lacunar infarcts and white matter hyperintensities. Regional analyses showed that, in particular, the connectivity strength of prefrontal, occipital, striatal, and thalamic nodes correlated with gait speed. CONCLUSION:Poorer physical performance is related to disrupted white matter network connectivity in memory clinic patients with vascular brain injury. The associations of these network abnormalities are partially independent of visible vascular injury. J Am Geriatr Soc 67:1880-1887, 2019.

SUBMITTER: Verwer JH

PROVIDER: S-EPMC6851861 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network.

Verwer Jurre H JH Reijmer Yael D YD Koek Huiberdina L HL Biessels Geert Jan GJ

Journal of the American Geriatrics Society 20190528 9

<h4>Background/objectives</h4>Memory clinic patients commonly also have declined physical performance. This may be attributable to white matter injury, due to vascular damage or neurodegeneration. Quantifying white matter injury is made possible by new magnetic resonance imaging (MRI) techniques, including diffusion-weighted imaging (DWI) of network connectivity. We investigated whether physical performance in memory clinic patients is related to white matter network connectivity.<h4>Design</h4> ...[more]

PMID: 31135061

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Project description:Background and purpose: Cerebral microinfarcts (CMIs) are associated with cognitive impairment and dementia. CMIs might affect cognitive performance through disruption of cerebral networks. We investigated in memory clinic patients whether cortical CMIs are clustered in specific brain regions and if presence of cortical CMIs is associated with reduced white matter (WM) connectivity in tracts projecting to these regions. Methods:164 memory clinic patients with vascular brain injury with a mean age of 72 ± 11 years (54% male) were included. All underwent 3 tesla MRI, including a diffusion MRI and cognitive testing. Cortical CMIs were rated according to established criteria and their spatial location was marked. Diffusion imaging-based tractography was used to reconstruct WM connections and voxel based analysis (VBA) to assess integrity of WM directly below the cortex. WM connectivity and integrity were compared between patients with and without cortical CMIs for the whole brain and regions with a high CMI burden. Results:30 patients (18%) had at least 1 cortical CMI [range 1-46]. More than 70% of the cortical CMIs were located in the superior frontal, middle frontal, and pre- and postcentral brain regions (covering 16% of the cortical surface). In these high CMI burden regions, presence of cortical CMIs was not associated with WM connectivity after correction for conventional neuroimaging markers of vascular injury. WM connectivity in the whole brain and WM voxels directly underneath the cortical surface did not differ between patients with and without cortical CMIs. Conclusion:Cortical CMIs displayed a strong local clustering in highly interconnected frontal, pre- and postcentral brain regions. Nevertheless, WM connections projecting to these regions were not disproportionally impaired in patients with compared to patients without cortical CMIs. Alternative mechanisms, such as focal disturbances in cortical structure and functioning, may better explain CMI associated cognitive impairment.

Project description:ObjectiveRisk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE.MethodsOne hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry).ResultsHigher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation).ConclusionsThese preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

Project description:Background and purposeSecondary-progressive MS is characterized by reduced acute inflammation and contrast enhancement but with increased axonal degeneration and cognitive/clinical disability that worsens with advanced disease. Relative recirculation, extracted from DSC is a surrogate measure of BBB integrity. We hypothesized that normal-appearing white matter relative recirculation is reduced in cognitively impaired compared with nonimpaired secondary-progressive MS, reflecting more advanced disease.Materials and methodsCognitive performance was classified as impaired or nonimpaired by use of Minimal Assessment of Cognitive Function In MS test components. Demographic data, brain parenchymal fraction, WM lesion fraction, and weighted mean normal-appearing white matter relative recirculation were compared in cognitively dichotomized groups. Univariate and multivariate logistic regressions were used to study the association between cognitive test results and normal-appearing white matter relative recirculation.ResultsThe mean (SD) age of 36 patients with secondary-progressive MS studied was 55.9 ± 9.3 years; 13 of 36 (36%) patients were male. A highly significant difference between normal-appearing white matter relative recirculation and WM lesion relative recirculation was present for all patients (P < .001). Normal-appearing white matter relative recirculation in impaired patients was significantly lower than in nonimpaired subjects for the Symbol Digit Modalities Test (P = .007), Controlled Word Association Test (P = .008), and Paced Auditory Serial Addition Test (P = .024). The Expanded Disability Status Scale demonstrated an inverse correlation with normal-appearing white matter relative recirculation (r = -0.319, P = .075). After adjustment for confounders, significant normal-appearing white matter relative recirculation reduction persisted for the Symbol Digit Modalities Test (P = .023) and the Paced Auditory Serial Addition Test (P = .047) but not for the Controlled Word Association Test (P = .13) in impaired patients.ConclusionsSignificant normal-appearing white matter relative recirculation reduction exists in cognitively impaired patients with secondary-progressive MS, localizing to the domains of processing speed and working memory.

Project description:It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition.

Project description:Cerebral small vessel diseases play a crucial role in both vascular and non-vascular dementias. The location of white matter hyperintensities (WMHs), a neuroimaging marker of cerebral small vessel disease, has been found to vary between different types of dementias, and those in the basal ganglia (BG) have been particularly associated with vascular cognitive impairment (VCI). However, anatomical variation of WMHs across BG nuclei and its effect on brain network dysconnectivity has not been clearly elucidated. The study sample consisted of 40 patients with amnestic mild cognitive impairment (aMCI), 40 with subcortical vascular MCI (SVMCI), and 40 healthy control subjects. We examined the volume of WMH using T2-weighted magnetic resonance imaging. We also assessed the disturbances in BG-cortical communication by measuring resting-state functional connectivity (rsFC) from the functional magnetic resonance imaging signal. WMHs were more pronounced in the SVMCI group particularly in the caudate regions. In SVMCI patients, while higher WMHs in the dorsal caudate correlated with weaker FC with executive control regions and worse immediate recall performance, WMHs in the ventral caudate were associated with weaker FC with anterior default mode regions and worse delayed recall performance. In contrast, in aMCI patients, BG WMHs were not correlated with their changes in functional connectivity changes, which showed weaker connectivity with almost all BG structures, rather than restricting to specific BG subdivisions as observed in the SVMCI group. Our findings demonstrate that heterogeneously distributed BG WMHs are associated with changes in functional network interactions and verbal episodic memory performance only in SVMCI patients, which establishes a link between cerebrovascular-related structural abnormality, functional integrity of BG circuits, and episodic memory impairments in SVMCI, and may reflect a differential role of the cerebrovascular pathology in disrupting network-level communications and cognition between Alzheimer's and subcortical vascular dementia.

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Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network.

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Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network.

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