Bidirectional mediation of bone mineral density and brain atrophy on their associations with gait variability.

This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (ß = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (ß = 0.147, FDR = 0.006), sensorimotor cortex (ß = 0.153, FDR = 0.006), and entorhinal cortex (ß = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Analysis of gait pattern related to high cerebral small vessel disease burden using quantitative gait data from wearable sensors.

BACKGROUND AND OBJECTIVES: Sensor-based wearable devices help to obtain a wide range of quantitative gait parameters, which provides sufficient data to investigate disease-specific gait patterns. Although cerebral small vessel disease (CSVD) plays a significant role in gait impairment, the specific gait pattern associated with a high burden of CSVD remains to be explored. METHODS: We analyzed the gait pattern related to high CSVD burden from 720 participants (aged 55-65 years, 42.5 % male) free of neurological disease in the Taizhou Imaging Study. All participants underwent detailed quantitative gait assessments (obtained from an insole-like wearable gait tracking device) and brain magnetic resonance imaging examinations. Thirty-three gait parameters were summarized into five gait domains. Sparse sliced inverse regression was developed to extract the gait pattern related to high CSVD burden. RESULTS: The specific gait pattern derived from several gait domains (i.e., angles, phases, variability, and spatio-temporal) was significantly associated with the CSVD burden (OR=1.250, 95 % CI: 1.011-1.546). The gait pattern indicates that people with a high CSVD burden were prone to have smaller gait angles, more stance time, more double support time, larger gait variability, and slower gait velocity. Furthermore, people with this gait pattern had a 25 % higher risk of a high CSVD burden. CONCLUSIONS: We established a more stable and disease-specific quantitative gait pattern related to high CSVD burden, which is prone to facilitate the identification of individuals with high CSVD burden among the community residents or the general population.

The Effects of Brain Magnetic Resonance Imaging Indices in the Association of Olfactory Identification and Cognition in Chinese Older Adults.

Background: Olfactory identification dysfunction frequently occurs in individuals with cognitive decline; however, a pathological mechanism linking the two has not been discovered. We aimed to study the association between olfactory identification and cognitive function, and determine the effects of brain regions atrophy therein. Methods: A total of 645 individuals (57.5% were female) from the Taizhou Imaging Study, who underwent cognitive and olfactory identification measurements, were included. A subsample of participants underwent brain magnetic resonance imaging (n = 622). Cognition was assessed with a neuropsychological battery. Olfactory identification was measured using a 12-item Sniffin' Sticks test. Beta and logistic regressions were used to elucidate the association between olfactory identification and cognition, and the effects of brain regions atrophy in this association. Results: Dementia was diagnosed in 41 (6.4%) individuals (mean age = 64.8 years), and mild cognitive impairment (MCI) in 157 (24.3%) individuals (mean age = 64.4 years). Olfactory identification was associated with MMSE and MoCA (both P < 0.001) and specific cognitive domains (memory, executive function, visuospatial function, and language; all P < 0.05). Higher olfactory identification was associated with lower likelihood of MCI and dementia (P < 0.05). The amygdala volume was significantly related to olfactory identification, MMSE, MoCA, and language, and could attenuate the association between olfactory identification and cognitive function. Conclusion: The association between olfactory identification and cognition can be partly attributable to differences in amygdala volume, suggesting that the amygdala could be a shared neural substrate that links olfactory identification and cognitive function. Limitations of this study include that all these results were based on a cross-sectional study.

Cross-sectional associations between cortical thickness and independent gait domains in older adults.

BACKGROUND: Although the prevalence of gait disturbance is increasing with population aging, our understanding of its underlying neural basis is still limited. The precise brain regions linked to specific gait domains have not been well defined. In this study, we aim to investigate the associations of cortical thickness and different gait domains, and to explore whether these associations could be explained by cerebral small vessel disease. METHODS: A total of 707 community-dwelling participants from the Taizhou Imaging Study (mean age: 60.2 ± 3.0 years, 57.4% female) were involved. All participants underwent brain MRI and gait assessment. We obtained quantitative gait parameters using wearable devices and then summarized them into three independent gait domains through factor analysis. Cortical thickness was analyzed and visualized using FreeSurfer and Surfstat. RESULTS: Three independent domains (pace, rhythm, and variability) were summarized from 12 gait parameters. Among gait domains, poorer pace was associated with the thinner cortical thickness of multiple regions, which included areas related with motor function (e.g., the primary motor cortex, premotor cortex, and supplementary motor area), sensory function (e.g., the postcentral gyrus and paracentral lobule), visuospatial attention (e.g., the lateral occipital cortex and lingual gyrus), and identification and cognition (e.g., the fusiform gyrus and entorhinal cortex). Such a relationship was only slightly attenuated after adjustment for cerebrovascular risk factors and cerebral small vessel disease. No statistically significant association was found between cortical thickness and the rhythm or variability domains. CONCLUSIONS: Poorer pace is independently associated with thinner cortical thickness in areas important for motor, sensory, cognitive function, and visuospatial attention. Our study emphasizes the importance of cortical thickness in gait control and adds value in investigating neural mechanisms of gait.

Spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels in 204 countries and territories from 1990 to 2019.

Exposure to household air pollution from solid fuels (HAP) is associated with stroke. However, few studies have assessed stroke burden attributable to HAP globally and made comparisons across countries. We aimed to estimate the spatiotemporal trends in stroke burden and mortality attributable to household air pollution from solid fuels (HAP) in 204 countries and territories from 1990 to 2019. Data on stroke burden and mortality attributable to HAP from 1990 to 2019 were obtained from Global Burden of Disease Study 2019. We estimated the numbers and age-standardized rates (ASRs) of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) by sex, age, and subtype, at global, regional, and national levels. Estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends in ASDR and ASMR from 1990 to 2019. In 2019, globally, 14.7 million DALYs and 0.6 million deaths were caused by stroke attributable to HAP. The corresponding ASDR and ASMR increased with age, were highest in males and for intracerebral hemorrhage, with highest ASRs in the low sociodemographic index (SDI) regions and Solomon Islands, and varied greatly at the national level. From 1990 to 2019, the corresponding EAPCs in ASDR and ASMR were -4.00 (95% confidence interval [CI]: -4.21 to -3.80) and -4.12 (95% CI: -4.37 to -3.87), respectively. Stroke burden attributable to HAP decreased in all age groups. Females had a lower decreasing trend in ASDR and ASMR, compared with males. The decline was more significant for subarachnoid hemorrhage, while proportions of ischemic stroke in the numbers of stroke burden increased worldwide and in all SDI regions. Although most of countries and territories were in a decreasing trend in ASRs over the past three decades, Zimbabwe and Philippines showed an undesirable increased trend. Stroke burden attributable to HAP is still pronounced in males, old-age populations, low-income countries, and for intracerebral hemorrhage. Despite its decreasing spatiotemporal trends in most countries, continued efforts on HAP control are needed to reduce related stroke burden, especially in those countries with increased trends.

Stroke burden and mortality attributable to ambient fine particulate matter pollution in 195 countries and territories and trend analysis from 1990 to 2017.

BACKGROUND: Fine particulate matter (PM2.5) exposure is associated with stroke incidence and mortality. However, the global distribution and trends of stroke burden and mortality attributable to PM2.5 are rarely studied. We estimated the spatial patterns and temporal trends of PM2.5-attributable stroke burden in 195 countries and territories from 1990 to 2017. METHODS: Detailed data on stroke burden attributable to PM2.5 were extracted from the Global Burden of Disease Study (GBD) 2017. The numbers and age-standardized rates of stroke disability-adjusted life years (DALYs) and mortality (ASDR and ASMR) were estimated by age, sex, subtype, region, and country. Temporal trends in ASDR and ASMR were analyzed using estimated annual percentage change (EAPC). RESULTS: Globally, in 2017, 10.5 million DALYs and 0.4 million deaths related to stroke were attributable to PM2.5. The corresponding ASDR and ASMR increased with age, were highest in males and for intracerebral hemorrhage, and varied greatly across countries, with the largest burden in high-middle sociodemographic index (SDI) regions and East Asia. The global ASDR and ASMR decreased by 7.2% and 12.2% from 1990 to 2017, with EAPCs of -0.42 (95% confidence interval [CI]: -0.55, -0.28) and -0.57 (95% CI: -0.72, -0.42), respectively. Age-specific stroke burden rates declined significantly, except in the middle-aged population. The decrease was more pronounced in women and for subarachnoid hemorrhage, while proportions of ischemic stroke burden increased globally and in all SDI regions. Most geographic regions achieved significant declines in ASDR and ASMR since 1990; however, Asia and approximately 30% of countries and territories, especially in low-income countries, showed undesirable increasing trends. CONCLUSIONS: The patterns and trends were heterogeneous across countries. Strengthened and tailored approaches for stroke prevention and air pollution management are still needed to reduce the disease burden associated with PM2.5, particularly in males, middle-age populations, and low-income countries and for ischemic stroke.