Development of anxiety in early Parkinson's disease: A clinical and biomarker study.

BACKGROUND: Anxiety affects approximately 40% of Parkinson's disease (PD) patients. However, little is known about its predictors and development over time. OBJECTIVE: To identify the clinical factors and biomarkers associated with development of anxiety in patients with newly diagnosed PD, and to test which risk factors predict increases in anxiety over time. METHODS: Data from the Parkinson's Progression Markers Initiative (PPMI) were utilized. The primary outcome was the State-Trait Anxiety Inventory (STAI). Covariates were demographics, motor and non-motor symptoms, cognitive functions, dopamine transporter imaging data, and cerebrospinal fluid (CSF) biomarkers. We examined the association of risk factors at baseline and over 4 years with changes in anxiety scores over time. RESULTS: A total of 252 patients met the inclusion criteria (mean age: 61.36 years, SD 9.53). At year 4, 42 patients had developed anxiety. Baseline predictors of increase in anxiety scores were greater autonomic dysfunction, dysexecutive function, CSF t-tau levels, excessive daytime sleepiness, and lower olfactory function scores but not motor scores. Over 4 years, change in anxiety scores correlated with deterioration in overall cognitive function, excessive daytime sleepiness, as well as depression and disability, and to a lesser degree worsening of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scores and caudate dopaminergic uptake changes. CONCLUSIONS: These findings suggest that development of anxiety in PD is not primarily based on a dopaminergic deficit in the basal ganglia but related to non-dopaminergic or extrastriatal pathology. Early dysexecutive function predicts development of anxiety but increase in anxiety levels correlates most strongly with more global cognitive decline.

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs). METHODS: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses. RESULTS: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370). DISCUSSION: These results do not suggest an association between GAS exposure and development of tics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder.

Association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis.

BACKGROUND: Trial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients. METHODS: MEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: Of 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10-1.58, n = 15 studies, I2 = 0%) and 1.23 (95%CI 0.99-1.54, n = 14, I2 = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47-8.76, n = 2, I2 = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09-6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83-8.62, n = 3, I2 = 77.9%) and 3.34 (95%CI 0.79-14.1, n = 4, I2 = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65-1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I2 = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence. CONCLUSION: Atherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.

Longitudinal analysis of the impact of loneliness on cognitive function over a 20-year follow-up.

Background: Loneliness and cognitive impairment are both commonly experienced by older old people, but evidence for the association between these has been inconsistent. Moreover, most evidence has been cross-sectional in nature and largely based on studies with relatively young later life age groups rather than 'the oldest old'. We aimed to test the potential impact of loneliness amongst older old people on their cognitive function over a 20-year period.Method: Data were drawn from wave 3 to wave 10 of the Cambridge City over-75s Cohort (CC75C) study. The impact of loneliness on transition between normal and impaired cognitive states was examined by multi-state modelling. The associations between loneliness changes and cognitive function decline were tested by using generalized estimating equation (GEE) with an independent working correlation structure. Missing data were imputed by using multiple imputation chained equations.Results: At wave 3, 713 participants were interviewed, of whom 657 (92%) had Mini-Mental State Examination (MMSE) assessments. Of individuals who had an MMSE score, approximately one quarter reported feeling lonely, and another 16% felt slightly lonely. The prevalence of feeling lonely or slightly lonely varied between waves. Results from multi-state modelling indicated that loneliness was not related to cognitive function transitions, and results from the GEE model showed that loneliness was not significantly associated with cognitive function decline after adjusting for cohort effects, follow-up time, sex, education, and interaction terms for sex, education and time.Conclusions: Loneliness did not exert long-term harmful effects on cognitive function in the oldest old.

Mortality risk of loneliness in the oldest old over a 10-year follow-up.

Objective: To investigate the impact of loneliness on all-cause mortality in the oldest old population over a 10-year follow-up.Method: Participants were from the third wave of the Cambridge City over-75s Cohort (CC75C) study, a population-based longitudinal study of older people aged 75 or over. Loneliness was measured two further times. At each wave, participants were asked how often they felt lonely and the answers were divided into three levels: not lonely, slightly lonely and lonely. The relationship between loneliness and all-cause mortality was examined using Cox regression with loneliness as a time-varying predictor. The association was adjusted for socio-demographic factors, number of chronic diseases, functional ability and depression.Results: Seven hundred thirteen participants were seen at wave 3 (out of 2166 at baseline), of whom 665 had data on loneliness. The prevalence of feeling slightly lonely and lonely was 16% and 25%, respectively. Vital status was followed for a further 10 years. A total of 562 participants died during the follow-up. After adjusting for age, sex and other socio-demographic factors, loneliness was associated with a 20% increased risk of mortality (HR: 1.2, 95% CI: 1.0-1.6). The association was disappeared after further adjusting for health conditions and depression (HR: 1.0, 95% CI: 0.8-1.4). Individuals who reported being slightly lonely were not at risk of mortality.Conclusions: The association between loneliness and mortality was fully explained by health conditions, suggesting that in the very old age, health problem is the proximal risk factor for mortality.

Is loneliness associated with increased health and social care utilisation in the oldest old? Findings from a population-based longitudinal study.

OBJECTIVES: The present study aimed to examine the impact of loneliness on health and social care service use in the oldest old over a 7-year follow-up. DESIGN: Prospective study. SETTING: UK population-based cohort. PARTICIPANTS: 713 people aged 80 years or older were interviewed at wave 3 of the Cambridge City over-75s Cohort Study. Of these, 665 provided data on loneliness. During 7 years' follow-up, 480 participants left the study, of which 389 due to death. 162 still in the study answered the loneliness question. MAIN OUTCOME MEASURE: Use of health and social care services, assessed at each wave from wave 3 to wave 5. RESULTS: At wave 3, of 665 participants who had data on loneliness, about 60% did not feel lonely, 16% felt slightly lonely and 25% felt lonely. Being slightly lonely at wave 3 was associated with a shorter time since last seeing a general practitioner (ß=-0.5, 95% CI: -0.8 to -0.2); when examining the association between time-varying loneliness and health and social care usage, being lonely was associated with three times greater likelihood of having contact with community nurses and using meals on wheels services (community nurse contact: incidence rate ratio (IRR)=3.4, 95% CI: 1.4 to 8.7; meals on wheels service use: IRR=2.5, 95% CI: 1.1 to 5.6). No associations between loneliness and other health and social care services use were found. CONCLUSION: Loneliness was a significant risk factor for certain types of health and social care utilisations, independently of participants' health conditions, in the oldest old. Study findings have several implications, including the need for awareness-raising and prevention of loneliness to be priorities for public health policy and practice.