Impact of small vessel disease in the brain on gait and balance

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71–74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI. We investigated the impact of individual SVD markers (white matter hyperintensity – WMH, microbleeds, lacunes, enlarged perivascular spaces, brain atrophy) as seen on structural brain MRI and of a global SVD score on the patients’ performance. A regression model revealed that age, sex, and hypertension significantly explained gait speed. Among SVD markers white matter hyperintensity (WMH) score or volume were additional significant and independent predictors of gait speed in the regression model. A similar association was seen with the global SVD score. Our study confirms a negative impact of SVD-related morphologic brain changes on gait speed in addition to age, sex and hypertension independent from brain atrophy. The presence of WMH seems to be the major driving force for SVD on gait impairment in healthy elderly subjects

Aging associated changes in the motor control of ankle movements in the brain.

Although age-related gait changes have been well characterized, little is known regarding potential functional changes in central motor control of distal lower limb movements with age. We hypothesized that there are age-related changes in brain activity associated with the control of repetitive ankle movements, an element of gait feasible for study with functional magnetic resonance imaging. We analyzed standardized functional magnetic resonance imaging data from 102 right-foot dominant healthy participants aged 20-83 years for age-associated effects using FSL and a meta-analysis using coordinate-based activation likelihood estimation. For the first time, we have confirmed age-related changes in brain activity with this gait-related movement of the lower limb in a large population. Increasing age correlated strongly with increased movement-associated activity in the cerebellum and precuneus. Given that task performance did not vary with age, we interpret these changes as potentially compensatory for other age-related changes in the sensorimotor network responsible for control of limb function

Aging associated changes in the motor control of ankle movements in the brain

Although age-related gait changes have been well characterized, little is known regarding potential functional changes in central motor control of distal lower limb movements with age. We hypothesized that there are age-related changes in brain activity associated with the control of repetitive ankle movements, an element of gait feasible for study with functional magnetic resonance imaging. We analyzed standardized functional magnetic resonance imaging data from 102 right-foot dominant healthy participants aged 20-83years for age-associated effects using FSL and a meta-analysis using coordinate-based activation likelihood estimation. For the first time, we have confirmed age-related changes in brain activity with this gait-related movement of the lower limb in a large population. Increasing age correlated strongly with increased movement-associated activity in the cerebellum and precuneus. Given that task performance did not vary with age, we interpret these changes as potentially compensatory for other age-related changes in the sensorimotor network responsible for control of limb function. © 2014 Elsevier Inc

Differences and similarities in the evolution of morphologic brain abnormalities between paediatric and adult-onset multiple sclerosis

BACKGROUND: Paediatric-onset multiple sclerosis (pMS) is multiple sclerosis (MS) occurring before the age of 18 years and may present and develop differently from adult-onset MS (aMS). Whether there are also differences regarding the accrual of brain changes is largely unknown. METHODS: We compared the evolution of the T2- and T1-lesion load (LL), the black hole ratio (BHR), and annualised brain volume change (aBVC) between 21 pMS patients (age at onset: 14.4±2.3 years) and 21 aMS patients (age at onset: 29.4±6.5 years) matched for disease duration (pMS: 1.0±1.8 years; aMS: 1.6±1.7 years, p=0.27). Follow-up was for 4.2±3.7 years in pMS and 3.1±0.6 years in aMS. Clinical comparisons included the course of disability assessed with the Expanded Disability Status Scale (EDSS) score and annualised relapse rate (ARR). RESULTS: At baseline, pMS and aMS had similar EDSS, T1-LL, BHR, whereas T2-LL was higher in aMS (aMS: 9.2±11.6 ccm; pMS: 4.1±6.2 ccm, p=0.02). The change of T2-LL and T1-LL during the observation period was similar in both groups. At follow-up, disability was lower in pMS (EDSS score in pMS: 0.9±0.9; aMS: 1.7±1.3, p=0.04), despite a significantly higher accrual of destructive brain lesions (BHR in pMS: 23.7±23.7%; aMS: 5.9±4.0%, p=0.02) and a similar rate of brain volume loss. CONCLUSION: Our observation of a morphologically more aggressive disease evolution paralleled by less disability in pMS than in aMS (defined using EDSS) suggests a higher compensatory capacity in pMS. This fact may obscure the need for treatment of pMS patients with disease modifying treatments (DMTs) based solely on clinical observation

Soluble TREM2 is elevated in Parkinson’s disease subgroups with increased CSF tau

Abstract Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and affects 1% of the population above 60 years old. Although Parkinson’s disease commonly manifests with motor symptoms, a majority of patients with Parkinson’s disease subsequently develop cognitive impairment, which often progresses to dementia, a major cause of morbidity and disability. Parkinson’s disease is characterized by α-synuclein accumulation that frequently associates with amyloid-β and tau fibrils, the hallmarks of Alzheimer’s disease neuropathological changes; this co-occurrence suggests that onset of cognitive decline in Parkinson’s disease may be associated with appearance of pathological amyloid-β and/or tau. Recent studies have highlighted the appearance of the soluble form of the triggering receptor expressed on myeloid cells 2 (sTREM2) receptor in CSF during development of Alzheimer’s disease. Given the known association of microglial activation with advancing Parkinson’s disease, we investigated whether CSF and/or plasma sTREM2 differed between CSF biomarker-defined Parkinson’s disease participant subgroups. In this cross-sectional study, we examined 165 participants consisting of 17 cognitively normal elderly subjects, 45 patients with Parkinson’s disease with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF amyloid-β and tau levels revealed that CSF sTREM2 concentrations were elevated in Parkinson’s disease subgroups with a positive tau CSF biomarker signature, but not in Parkinson’s disease subgroups with a positive CSF amyloid-β biomarker signature. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in Parkinson’s disease.</jats:p