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Introduction: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS)., Methods: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters., Results: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed., Discussion: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments., Highlights: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.

Purpose: This paper aims to examine the effectiveness of structural imaging as an aid in the diagnosis of Parkinson's disease (PD)., Methods: High-resolution T 1 -weighted magnetic resonance imaging was performed in 72 patients with idiopathic PD (mean age, 61.08 years) and 73 healthy subjects (mean age, 58.96 years). The whole brain was parcellated into 95 regions of interest using composite anatomical atlases, and region volumes were calculated. Three diagnostic classifiers were constructed using binary multiple logistic regression modeling: the (i) basal ganglion prior classifier, (ii) data-driven classifier, and (iii) basal ganglion prior/data-driven hybrid classifier. Leave-one-out cross validation was used to unbiasedly evaluate the predictive accuracy of imaging features. Pearson's correlation analysis was further performed to correlate outcome measurement using the best PD classifier with disease severity., Results: Smaller volume in susceptible regions is diagnostic for Parkinson's disease. Compared with the other two classifiers, the basal ganglion prior/data-driven hybrid classifier had the highest diagnostic reliability with a sensitivity of 74%, specificity of 75%, and accuracy of 74%. Furthermore, outcome measurement using this classifier was associated with disease severity., Conclusions: Brain structural volumetric analysis with multiple logistic regression modeling can be a complementary tool for diagnosing PD.

Objective: The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM)., Methods: We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses., Results: A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at multiple brain areas including the frontal, temporal and occipital lobes, precuneus and cerebellum., Conclusions: Our study showed GMV changes in CMwMO patients compared to the CMwoMO patients. These three cerebral regions accounted for significant variance in analgesics use frequency. Moreover, the GMV of the orbitofrontal cortex was predictive of the response to MO treatments., (© International Headache Society 2016.)

Background: Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH., Methods: Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed., Results: Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-of-bout scans, in-bout scans revealed decreased hypothalamic FC with the medial frontal gyrus, precuneus, and cerebellar areas (tonsil, declive and culmen). Additionally, the annual bout frequency correlated significantly with the hypothalamic FC in the cerebellar culmen (r=-0.576, p=0.02) and cerebellar declive (r=-0.522, p=0.038)., Conclusions: Our findings suggest that in CH, FC differences between the hypothalamus and its regional distribution extends beyond traditional pain processing areas, primarily to the cerebellar, frontal and occipital areas. These changes may be important and associated with CH pathophysiology., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The present study aimed to determine whether a recently proposed cerebral small vessel disease (CSVD) classification scheme could differentiate the 5-year all-cause mortality in middle-to-old aged asymptomatic CSVD. Stroke-free and non-demented participants recruited from the community-based I-Lan Longitudinal Aging Study underwent baseline brain magnetic resonance imaging (MRI) between 2011 and 2014 and were followed-up between 2018 and 2019. The study population was classified into control (non-CSVD) and CSVD type 1–4 groups based on MRI markers. We determined the association with mortality using Cox regression models, adjusting for the age, sex, and vascular risk factors. A total of 735 participants were included. During a mean follow-up of 5.7 years, 62 (8.4%) died. There were 335 CSVD type 1 (57.9 ± 5.9 years), 249 type 2 (65.6 ± 8.1 years), 52 type 3 (67.8 ± 9.2 years), and 38 type 4 (64.3 ± 9.0 years). Among the four CSVD types, CSVD type 4 individuals had significantly higher all-cause mortality (adjusted hazard ratio = 5.0, 95% confidence interval 1.6–15.3) compared to controls. This novel MRI-based CSVD classification scheme was able to identify individuals at risk of mortality at an asymptomatic, early stage of disease and might be applied for future community-based health research and policy. [ABSTRACT FROM AUTHOR]

Background: The increase of headache frequency is associated with higher headache related disability and lower quality of life in patients with migraine. However, the pathophysiology of migraine progression, persistence, or remission is elusive. The purpose of this study is to identify the brain signatures that are predictive of the long-term outcomes among patients with high-frequency migraine (HFM: 10–30 headache days/month). Methods: We prospectively enrolled patients with HFM and healthy controls and collected their baseline clinical profiles and brain-MRI data at first visit. We longitudinally followed the patients and determined their outcomes at 2-year follow-up. Good outcome was defined as ≥50% reduction of baseline headache days and poor outcome was defined as reduction < 50% or frequency increase. Voxel-based morphometry was used to study gray matter volume (GMV), and structural covariance was used to investigate structural connectivity. Results: Among 56 patients with HFM, 37 had good outcome and 19 poor outcome. Compared to the healthy controls (n = 37), patients with poor outcome had decreased GMV over the left posterior cingulate gyrus, and increased GMV over the bilateral cerebellum and the right precentral gyrus. Further, patients with poor outcome had greater GMV over the right and the left cerebella compared to patients with good outcome, and the GMVs of the cerebella were correlated to 2-year headache frequencies (right: r = 0.38, P = 0.005; left: r = 0.35, P = 0.009). Structural connectivity were increased between the cerebellum and the cuneus, the calcarine cortex, and the temporal lobe, respectively, in patients with poor outcome, and was decreased between the cerebellum and the prefrontal cortex in patients with poor outcome. The structural covariance integrities between the right cerebellum and the right cuneus were correlated to 2-year headache frequencies (r = 0.36, P = 0.008). Conclusions: Structural volume and connectivity changes of the cerebellum may underlie headache persistence in patients with HFM. [ABSTRACT FROM AUTHOR]

Background: Despite evidently distinct symptoms, tension-type headache (TTH) and migraine are highly comorbid and exhibit many similarities in clinical practice. The purpose of this study was to investigate whether both types of headaches are similar in brain morphology. Methods: Consecutive patients with TTH and age- and sex-matched patients with migraine and healthy controls were enrolled for brain magnetic resonance imaging examination. Patients with TTH were excluded if they reported any headache features or associated symptoms of migraine. Changes in gray matter (GM) volume associated with headache diagnosis (TTH vs. migraine) and frequency (episodic vs. chronic) were examined using voxel-based morphometry. The correlation with headache profile and the discriminative ability between TTH and migraine were also investigated for these GM changes. Results: In comparison with controls ( n = 43), the patients with TTH (25 episodic and 24 chronic) exhibited a GM volume increase in the anterior cingulate cortex, supramarginal gyrus, temporal pole, lateral occipital cortex, and caudate. The patients with migraine (31 episodic and 25 chronic) conversely exhibited a GM volume decrease in the orbitofrontal cortex. These GM changes did not correlate with any headache profile. A voxel-wise 2 × 2 factorial analysis further revealed the substantial effects of headache types and frequency in the comparison of GM volume between TTH and migraine. Specifically, the migraine group (vs. TTH) had a GM decrease in the superior and middle frontal gyri, cerebellum, dorsal striatum, and precuneus. The chronic group (vs. episodic group) otherwise demonstrated a GM decrease in the bilateral insula and anterior cingulate cortex. In receiver operating characteristic analysis, the GM volumes of the left superior frontal gyrus and right cerebellum V combined had good discriminative ability for distinguishing TTH and migraine (area under the curve = 0.806). Conclusions: TTH and migraine are separate headache disorders with different characteristics in relation to GM changes. The major morphological difference between the two types of headaches is the relative GM decrease of the prefrontal and cerebellar regions in migraine, which may reflect a higher allostatic load associated with this disabling headache. [ABSTRACT FROM AUTHOR]

Physical frailty has been recognized as a clinical syndrome resulting from declines in various physiological systems; however, the role of the central nervous system in the pathophysiology of frailty remains unclear. The I-Lan Longitudinal Aging Study randomly sampled community-dwelling people aged 50 or older for a brain magnetic resonance imaging study. All participants were assessed for frailty status (robust, prefrail, and frail) based on the presence of five frailty components: slow walking speed, muscle weakness, low physical activity, exhaustion and weight loss (Fried criteria). Gray matter volume (GMV) changes associated with frailty status and individual frailty components were examined. Overall, 456 participants (64.0 ± 8.5 years, 47.6% women) were included in this study. The prefrail ( n = 178, 39.0%) and frail ( n = 19, 4.2%) subjects were grouped for analysis. The prefrail-frail group showed reduced GMV, compared to the robust group ( n = 259, 56.8%), in the cerebellum, hippocampi, middle frontal gyri, and several other cerebral regions (corrected P < 0.05). Each frailty component was associated with GMV changes in functionally related brain areas. Hierarchical cluster analysis categorized these components into three subsets. Motor-related components, including weakness, low activity, and slowness, comprised one subset with a common cerebellar involvement. Exhaustion and weight loss were the other two subsets without cerebellar changes. To conclude, physical frailty is associated with a decreased reserve in specific brain regions, especially cerebellum. Further longitudinal studies are needed to explore if the cerebellum- and noncerebellum-based frailty components reflect a distinctive future risk for developing frailty. Hum Brain Mapp 36:3666-3676, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel-wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra-striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato-cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato-cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567-1584, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Despite diffuse tenderness, patients with fibromyalgia (FM) have reported a wide range of areas with musculoskeletal pain. This study investigated the neural structures and neuroanatomical networks associated with self-reported widespread pain in FM using magnetic resonance imaging. We collected clinical profiles and brain magnetic resonance imaging data of newly diagnosed patients with FM. A total of 138 patients with FM were divided into 3 subgroups based on the number of pain areas, with 3 to 8, 9 to 12, and 13 to 19 areas, respectively. Using voxel-based morphometry analysis, we first identified the neural structure that showed a trend of volumetric change across the 3 subgroups. We then used it as a candidate seed of interest with a seed-to-voxel analytical approach to explore the structural covariance (SC) networks of the whole brain. Finally, we studied the trend of changes in the distribution and strength of SC networks across subgroups of patients. We found a decreasing trend in the volumes of the right anterior insular cortex (rAIC) across the 3 subgroups that had an increased number of pain areas. An increasing trend in the number of neural substrates over the subcortical regions, especially the basal ganglion, showed SC to the rAIC, and a decreasing trend of SC strength was shown between the rAIC and the precuneus, frontal cortex, anterior and posterior cingulate, and lingual gyri, across the patient subgroups with increased pain areas. The rAIC and its altered connection with specific brain regions indicates widespread pain in patients with FM. [ABSTRACT FROM AUTHOR]

• A potential predictor of dementia conversion in cerebral small vessel disease (CSVD). • CSVD people with mobility frailty had higher risk of dementia at 5.7 years. • Mobility frailty may serve as one clinical marker for adverse outcomes of CSVD. • Mobility frailty might be involved in the mechanism of cognitive declines in CSVD Frailty has been shown to predict adverse outcomes in several diseases. We aimed to evaluate the associations between frailty profiles, both severity and subtype, and dementia risk in a community-based population with asymptomatic (without stroke and dementia) cerebral small vessel disease (CSVD). Individuals with asymptomatic CSVD were recruited from the community-based I-Lan Longitudinal Aging Study between 2011 and 2014 (baseline) and were followed up between 2018 and 2019. All participants underwent CSVD assessment by 3T brain MRI, as well as physical and cognitive assessments at baseline. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between each factor and dementia conversion at follow-up. Among 261 participants with asymptomatic CSVD (64.8 [50.0-89.1, 8.4] years; 136 [52.1%] men), 13 (5.0%) developed dementia during a mean follow-up of 5.7 (0.7) years. Dementia converters were less likely to be robust (30.8% vs. 61.5%) and more likely to be pre-frail/frail (69.2% vs. 38.5%) than non-converters (p = 0.040). Meanwhile, there was significantly more frequent mobility frailty (53.8% vs. 19.8%, p = 0.009), but a similar prevalence of non-mobility frailty in dementia converters compared with non-converters. Univariate analyses showed that neither frailty severity nor CSVD burden was associated with a higher risk of dementia; it was the frailty subtype, the mobility frailty, which was significantly associated with dementia conversion in participants with asymptomatic CSVD, with an odds-ratio of 4.8 (95% CI = 1.5–14.8, p = 0.007). The significance remained after adjusting for age, sex, education and baseline cognitive function, respectively. Mobility frailty was associated with a higher risk of incident dementia in individuals with subclinical CSVD. Mobility frailty might be involved in the pathology of cognitive decline in CSVD and potentially serve as a marker to identify people at risk of cognitive impairment at an early stage of CSVD. [ABSTRACT FROM AUTHOR]