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Introduction: Atypical parkinsonian syndromes (APS) are rare neurodegenerative syndromes for which parkinsonism is one significant feature. APS includes progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS). The diagnosis of APS remains reliant on clinical features with no available diagnostic or prognostic biomarker. Clinical scales remain the gold standard assessment measures in clinical trials and research. The lack of standardised approach for research cohorts has contributed to shortcomings in disease understanding and limits collaboration between researchers. The primary objectives of this study are to (1) establish an assessment protocol for parkinsonian syndromes and (2) to implement it at a single site to establish the viability and utility of populating a clinical and biological databank of patients with APS. Methods: The Monash Alfred Protocol for Assessment of APS was devised by expert consensus within a broad multidisciplinary team. Eligible patients are diagnosed as possible or probable PSP, MSA or CBS by a consultant neurologist with expertise in movement disorders. Participants will be assessed at recruitment and then annually for up to 3 years; individuals within 5 years of index symptom onset will also undergo a once-off 6-month assessment. Ethics and dissemination: Each participant or their legally authorised representative will provide informed written consent prior to commencement of the study. Data will be stored on a locally hosted Research Electronic Data Capture database. Trial registration number: Australian New Zealand Clinical Trials Registry (ANZCTN 12622000923763).
ABSTRACT
BACKGROUND: To examine the effect of frailty on cognitive decline independent of cerebral small vessel disease (cSVD) and brain atrophy, and whether associations between neuropathology and cognition differed depending on frailty status. METHODS: The Tasmanian Study of Cognition and Gait was a population-based longitudinal cohort study with data collected at 3 phases from 2005 to 2012. Participants aged 60-85 were randomly selected from the electoral roll. Various data were used to operationalize a 36-item frailty index (FI) at baseline. Brain MRI was undertaken to obtain baseline measures of neuropathology. A neuropsychological battery was used to assess cognition at each time point. Generalized linear mixed models were used to examine the effect of frailty and MRI measures on cognition over time. The associations between MRI measures and cognition were explored after stratifying the sample by baseline frailty status. All analyses were adjusted for age, sex, and education. RESULTS: A total of 385 participants were included at baseline. The mean age was 72.5 years (standard deviation [SD] 7.0), 44% were female (n = 171). In fully adjusted linear mixed models, frailty (FI × time ß -0.001, 95% confidence interval [CI] -0.003, -0.001, p = .03) was associated with decline in global cognition, independent of brain atrophy, and cSVD. The association between cSVD and global cognition was significant only in those with low levels of frailty (p = .03). CONCLUSION: These findings suggest that frailty is an important factor in early cognitive dysfunction, and measuring frailty may prove useful to help identify future risk of cognitive decline.
Subject(s)
Cerebral Small Vessel Diseases , Cognitive Dysfunction , Frailty , Neurodegenerative Diseases , Aged , Atrophy , Brain/diagnostic imaging , Cerebral Small Vessel Diseases/complications , Cognition , Cognitive Dysfunction/psychology , Female , Humans , Longitudinal Studies , MaleABSTRACT
INTRODUCTION: Greater double support time (DST) variability is associated with falls and memory decline. The underlying neurophysiological mechanisms of DST variability are poorly understood. Simple reaction time (SRT) variability, a measure of attention-processing speed is associated with falls and dementia and, may underlie greater DST variability. The aims of this study were to examine the association between SRT and DST variability and if SRT variability mediates the associations between poorer cognition/brain structure and DST variability. METHODS: Participants (n = 408) were community-dwelling older people without dementia (mean age 72.0 ± 7.0). DST variability was the standard deviation (SD) of DST, assessed with a walkway and averaged across steps of 6 walks. SRT variability was the SD of a button pressing task in response to a visual stimulus. Executive function and processing speed were assessed with neuropsychological tests. Magnetic Resonance Imaging was used to obtain cortical thickness (total and in frontal regions) and cerebral small vessel disease (cSVD). Multivariable linear regression models were used to examine the association between SRT and DST variability and if SRT variability mediated any associations of cognition/brain structure with DST variability. RESULTS: Greater SRT variability was associated with greater DST variability (p = 0.002). SRT variability partially mediated the association between poorer executive function and greater DST variability. Smaller mean thickness in orbitofrontal regions and greater cSVD burden were only associated with DST variability (p < 0.05), not with SRT variability (p > 0.05). CONCLUSIONS: Greater SRT variability, which may occur due to inefficient executive functioning, could be an underlying neurophysiological mechanism of greater DST variability.
Subject(s)
Cognition , Gait , Aged , Executive Function , Humans , Neuropsychological Tests , Reaction TimeABSTRACT
BACKGROUND: The contribution of cerebral small vessel disease (cSVD) to the pathogenesis of frailty remains uncertain. We aimed to examine the associations between cSVD with progression of frailty in a population-based study of older people. METHODS: People aged between 60 and 85 years were randomly selected form the electoral roll to participate in the Tasmanian Study of Cognition and Gait. Participants underwent self-reported questionnaires, objective gait, cognitive and sensorimotor testing over three phases ranging between 2005 and 2012. These data were used to calculate a 41-item frailty index (FI) at three time points. Baseline brain magnetic resonance imaging was performed on all participants to measure cSVD. Generalized mixed models were used to examine associations between baseline cSVD and progression of frailty, adjusted for confounders of age, sex, level of education, and total intracranial volume. RESULTS: At baseline (n = 388) mean age was 72 years (SD = 7.0), 44% were female, and the median FI score was 0.20 (interquartile range [IQR] 0.12, 0.27). In fully adjusted models higher burden of baseline white matter hyperintensity (WMH) was associated with frailty progression over 4.4 years (ß = 0.03, 95% CI: 0.01, 0.05; p = .004) independent of other SVD markers. Neither baseline infarcts (p = .23), nor microbleeds at baseline (p = .65) were associated with progression of frailty. CONCLUSIONS: We provide evidence for an association between baseline WMHs and progression of frailty. Our findings add to a growing body of literature suggesting WMH is a marker for frailty.
Subject(s)
Disease Progression , Frailty/epidemiology , White Matter/diagnostic imaging , Aged , Aged, 80 and over , Cerebral Small Vessel Diseases/diagnostic imaging , Female , Geriatric Assessment , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Tasmania/epidemiologyABSTRACT
Background: Frailty is a prevalent geriatric condition associated with poor health outcomes. The pathogenesis of frailty is incompletely understood. We aimed to evaluate the relationship between cerebral small vessel disease (SVD) and frailty. Methods: People aged between 60 and 85 years were randomly selected from the electoral roll into the Tasmanian Study of Cognition and Gait. Participants completed standardized questionnaires regarding medical history and underwent objective sensorimotor, gait, and cognitive testing. These data were used to calculate a frailty index score. Magnetic resonance imaging was performed on all participants to measure SVD. Automated quantification was used to measure white matter hyperintensities (WMH), with manual consensus for subcortical infarction (SI) and cerebral microbleeds (CMB). Multivariable linear regression was used to determine the association between SVD and frailty. Results: The mean age of the sample (n = 388) was 72.0 years (SD 7.0), 44% (172/388) were female and the median Frailty Index was 0.20 (interquartile range 0.12, 0.27). WMH, SI, and CMB in unadjusted models were positively associated with higher frailty scores (p < .05). In final models including all brain variables, higher burden of WMH (ß = 2.16; 95% confidence interval [CI] 0.75, 3.57; p = .003), but not SI (ß = 2.96; 95% CI -0.44, 6.35; p = .09) or CMB (ß = -0.46; 95% CI -4.88, 3.96; p = .84), was independently associated with a higher frailty score. Conclusions: We provide cross-sectional evidence for a positive association between larger burden of WMH and frailty. Longitudinal design is required to determine the temporality of this relationship.