The Association of Incident Dementia with Mortality in PD

Objective: To evaluate the association of incident dementia with mortality in a cohort of patients with idiopathic PD who were nondemented at baseline evaluation, controlling for extrapyramidal sign (EPS) severity at each study visit. Background: The development of dementia has been associated with reduced survival in PD. Because EPS severity is associated with both dementia and mortality in PD, the association of dementia with mortality may be confounded by disease severity. Methods: A cohort of patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of incident dementia and the total Unified PD Rating Scale (UPDRS) motor score with mortality in PD was examined using Cox proportional hazards models with time-dependent covariates. All analyses were adjusted for age at baseline, sex, years of education, ethnicity, and duration of PD. Results: Of 180 PD patients, 41 (22.8%) died during a mean follow-up period of 3.9 ± 2.2 years. Among those who died during the study period, 48.8% (20 of 41) became demented during follow-up, as compared to 23.0% (32 of 139) of those who remained alive. Both incident dementia (RR: 2.2, 95% CI: 1.1 to 4.5, p = 0.04) and the total UPDRS motor score at each study visit (RR: 1.04, 95% CI: 1.02 to 1.07, p = 0.001) were associated with mortality in PD when included in the same Cox model. Conclusions: Incident dementia has an independent effect on mortality when controlling for EPS severity. The development of dementia is associated with a twofold increased mortality risk in PD

Motor Impairment in PD: Relationship to Incident Dementia and Age

OBJECTIVE: To analyze the relationship of specific motor impairment in idiopathic PD to incident dementia. BACKGROUND: The total Unified PD Rating Scale (UPDRS) motor score at baseline has been associated with an increased risk of developing dementia in PD. METHODS: A cohort of 214 nondemented community-dwelling patients with PD was followed annually with neurologic and neuropsychological evaluations. The association of baseline motor impairment with incident dementia was analyzed using Cox proportional hazards models. Facial expression, tremor, rigidity, and bradykinesia were analyzed as part of subscore A (indicative of dopaminergic deficiency); speech and axial impairment were analyzed as part of subscore B (indicative of predominantly nondopaminergic deficiency). The correlation between the six motor domains and age was also analyzed. RESULTS: Of 173 patients followed for at least 1 year, 50 became demented according to the Diagnostic and Statistical Manual of Mental Disorders, revised 3rd edition (DSM III-R) criteria (mean follow-up, 3.6 +/- 2. 2 years). When both subscores A and B were entered into the Cox model, subscore B was associated with incident dementia (relative risk = 1.19; 95% CI, 1.09 to 1.30; p = 0.0001), in addition to gender, age, and education, whereas subscore A was not (relative risk = 1.03; 95% CI, 0.99 to 1.07; p = 0.19). Of the six motor domains, speech and bradykinesia were associated with incident dementia (p < 0.05), and axial impairment approached significance (p = 0.06). Only axial impairment was correlated with age (correlation coefficient = 0.32; p < 0.001). CONCLUSION: The findings suggest that motor impairment mediated predominantly by nondopaminergic systems is associated with incident dementia in PD. Axial impairment may be the result of a combined effect of the disease and the aging process

Memory and Executive Function Impairment Predict Dementia in Parkinson's Disease

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty-five out of 164 patients (27%) became demented during a mean follow-up of 3.7 ± 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87–0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59–0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77–0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73–0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD

Postural and intention tremors: Detailed clinical study of essential tremor vs. Parkinson’s disease

ABSTRACTBackground: An estimated 30-50% of essential tremor diagnoses are incorrect, and the true diagnosis in those patients is often Parkinson’s disease or other tremor disorders. There are general statements about the tremor in these essential tremor and Parkinson’s disease, but published data on the more subtle characteristics of tremor are surprisingly limited. Postural tremor may occur in both disorders, adding to the difficulty. There are several anecdotal impressions regarding specific features of postural tremor in essential tremor vs. Parkinson’s disease, including joint distribution (e.g., phalanges, metacarpal-phalangeal joints, wrist), tremor directionality (e.g., flexion-extension vs. pronation-supination), and presence of intention tremor. However, there is little data to support these impressions.Methods: In this cross-sectional study, 100 patients (essential tremor, 50 Parkinson’s disease) underwent detailed videotaped neurological examinations. Arm tremor was rated by a movement disorder neurologist who assessed severity and directionality across multiple joints. Results: During sustained arm extension, essential tremor patients exhibited more wrist than metacarpal-phalangeal and phalangeal joint tremor than did Parkinson’s disease patients (p&lt;0.001), and more wrist flexion-extension tremor than wrist pronation-supination tremor (p&lt;0.001). During the finger-nose-finger maneuver, intention tremor was present in approximately one in four (28%) essential tremor patients vs. virtually none (4%) of the Parkinson’s patients (p&lt;0.001).Conclusions: We evaluated the location, severity, and directionality of postural tremor in essential tremor and Parkinson’s disease, and the presence of intention tremor, observing several clinical differences. We hope that detailed phenomenological data on tremor in essential tremor and Parkinson’s disease will help practicing physicians delineate the two diseases

The "Head Snap": A Subtle Clinical Feature During the Finger–Nose–Finger Maneuver in Essential Tremor

Background:: Essential tremor is characterized by several hyperkinetic movements, including arm and head tremors.  We report another movement of the head in patients with essential tremor, which we term the "head snap." This was observed as a jerking motion of the head in some patients while they performed the finger-nose-finger maneuver. Methods:: We compared the prevalence of the head snap in essential tremor patients vs. Parkinson's disease patients. We also assessed the clinical correlates of the head snap.  Results:: Ten (20%) of 50 essential tremor patients exhibited a head snap of any severity (rating ≥0.5) vs. 0 of 50 Parkinson's disease patients (p = 0.001). Patients with head snap had more severe arm tremor on Archimedes spiral drawings (p = 0.019) and were more likely to have head tremor (p = 0.03) than those without it. Conclusions: This sign could be a useful aid in the clinical diagnosis of tremor.</p

Isotope ratio infrared spectroscopy analysis of water samples without memory effects

Rationale Since their introduction more than a decade ago, isotope ratio infrared spectroscopy (IRIS) systems have rapidly become the standard for oxygen (δ18O) and hydrogen (δ2H) isotope analysis of water samples. An important disadvantage of IRIS systems is the well-documented sample-to-sample memory effect, which requires each sample to be analyzed multiple times before the desired accuracy is reached, lengthening analysis times and driving up the costs of analyses. Methods We present an adapted set-up and calculation protocol for fully automated analysis of water samples using a Picarro L2140-i cavity ring-down spectroscopy instrument. The adaptation removes memory effects by use of a continuously moisturized nitrogen carrier gas. Water samples of 0.5 μL are measured on top of the water vapor background, after which isotope ratios are calculated by subtraction of the background from the sample peaks. Results With this new technique, single injections of water samples have internal precisions (1σ) below 0.05‰ for δ18O values and 0.1‰ for δ2H values, regardless of the isotope ratio of the previous sample. Precision is worse, however, when the isotope difference between the sample and background water is too large (i.e., exceeding approximately 9‰ for δ18O values and 70‰ for δ2H values). Isotope ratios show negligible drift across the four weeks within which the experiments were performed. The single-injection 1σ precision for 17O excess (Δ′17O) determined with this method is 60 per meg. Conclusions Our experiments demonstrate that by removing sample-to-sample memory effects with a moisturized carrier gas, the time for measurement of δ18O and δ2H values using an IRIS system can be reduced markedly without compromising the analytical precision and accuracy. Thorough replication is needed to achieve sufficiently low uncertainties for Δ′17O.ISSN:1097-0231ISSN:0951-419

Intensified microbial sulfate reduction in the deep Dead Sea during the early Holocene Mediterranean sapropel 1 deposition.

The hypersaline Dead Sea and its sediments are natural laboratories for studying extremophile microorganism habitat response to environmental change. In modern times, increased freshwater runoff to the lake surface waters resulted in stratification and dilution of the upper water column followed by microbial blooms. However, whether these events facilitated a microbial response in the deep lake and sediments is obscure. Here we investigate archived evidence of microbial processes and changing regional hydroclimate conditions by reconstructing deep Dead Sea chemical compositions from pore fluid major ion concentration and stable S, O, and C isotopes, together with lipid biomarkers preserved in the hypersaline deep Dead Sea ICDP-drilled core sediments dating to the early Holocene (ca. 10,000 years BP). Following a significant negative lake water balance resulting in salt layer deposits at the start of the Holocene, there was a general period of positive net water balance at 9500-8300 years BP. The pore fluid isotopic composition of sulfate exhibit evidence of intensified microbial sulfate reduction, where both δ34S and δ18O of sulfate show a sharp increase from estimated base values of 15.0‰ and 13.9‰ to 40.2‰ and 20.4‰, respectively, and a δ34S vs. δ18O slope of 0.26. The presence of the n-C17 alkane biomarker in the sediments suggests an increase of cyanobacteria or phytoplankton contribution to the bulk organic matter that reached the deepest parts of the Dead Sea. Although hydrologically disconnected, both the Mediterranean Sea and the Dead Sea microbial ecosystems responded to increased freshwater runoff during the early Holocene, with the former depositing the organic-rich sapropel 1 layer due to anoxic water column conditions. In the Dead Sea prolonged positive net water balance facilitated primary production and algal blooms in the upper waters and intensified microbial sulfate reduction in the hypolimnion and/or at the sediment-brine interface

A comparison of isotope ratio mass spectrometry and cavity ring‐down spectroscopy techniques for isotope analysis of fluid inclusion water

Rationale Online oxygen (δ18O) and hydrogen (δ2H) isotope analysis of fluid inclusion water entrapped in minerals is widely applied in paleo‐fluid studies. In the state of the art of fluid inclusion isotope research, however, there is a scarcity of reported inter‐technique comparisons to account for possible analytical offsets. Along with improving analytical precisions and sample size limitations, interlaboratory comparisons can lead to a more robust application of fluid inclusion isotope records. Methods Mineral samples—including speleothem, travertine, and vein material—were analyzed on two newly setup systems for fluid inclusion isotope analysis to provide an inter‐platform comparison. One setup uses a crusher unit connected online to a continuous‐flow pyrolysis furnace and an isotope ratio mass spectrometry (IRMS) instrument. In the other setup, a crusher unit is lined up with a cavity ring‐down spectroscopy (CRDS) system, and water samples are analyzed on a continuous standard water background to achieve precisions on water injections better than 0.1‰ for δ18O values and 0.4‰ for δ2H values for amounts down to 0.2 μL. Results Fluid inclusion isotope analyses on the IRMS setup have an average 1σ reproducibility of 0.4‰ and 2.0‰ for δ18O and δ2H values, respectively. The CRDS setup has a better 1σ reproducibility (0.3‰ for δ18O values and 1.1‰ for δ2H values) and also a more rapid sample throughput (<30 min per sample). Fluid inclusion isotope analyses are reproducible at these uncertainties for water amounts down to 0.1 μL on both setups. Fluid inclusion isotope data show no systematic offsets between the setups. Conclusions The close match in fluid inclusion isotope results between the two setups demonstrates the high accuracy of the presented continuous‐flow techniques for fluid inclusion isotope analysis. Ideally, experiments such as the one presented in this study will lead to further interlaboratory comparison efforts and the selection of suitable reference materials for fluid inclusion isotopes studies.ISSN:1097-0231ISSN:0951-419

Do risk factors for Alzheimer's disease predict dementia in Parkinson's disease? An exploratory study

The extent to which concomitant Alzheimer's disease (AD) is etiologically related to the development of dementia in Parkinson's disease (PD) remains controversial. We explored the association of four risk factors associated with AD, including head injury, smoking, hypertension, and diabetes mellitus, with incident dementia in PD. A cohort of 180 nondemented PD patients from the Washington Heights community in northern Manhattan, New York, completed a risk factor questionnaire at baseline and was followed annually with neurological and neuropsychological evaluations. The association of baseline variables with incident dementia was analyzed by using Cox proportional hazards models. All analyses controlled for age at baseline, gender, years of education, duration of PD, and total Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline. Of 180 patients (mean age, 71.0 ± 10.3 years), 52 (29%) became demented during a mean follow-up period of 3.6 ± 2.2 years. Head injury risk ratio ([RR] 0.9; 95% confidence interval [CI], 0.4–2.2; P = 0.9), hypertension (RR, 0.7; 95% CI, 0.4–1.4, P = 0.3), and diabetes mellitus (RR, 0.8; 95% CI, 0.3–2.3; P = 0.7) were not significantly associated with incident dementia in the Cox models. Patients who reported having ever smoked were at increased risk for the development of dementia compared with nonsmokers (RR, 2.0; 95% CI, 1.0–3.9; P = 0.05). Current smoking was significantly associated with incident dementia (RR, 4.5; 95% CI, 1.2–16.4; P = 0.02), whereas past smoking approached significance (RR, 1.9; 95% CI, 0.9–3.7; P = 0.07). Although an inverse association between smoking and PD has been reported in several studies, our study showed a positive association between smoking and dementia in the setting of PD. The association of smoking with incident dementia in PD deserves further study

Combined Effect of Age and Severity on the Risk of Dementia in Parkinson's Disease

Age and severity of extrapyramidal signs have been consistently associated with incident dementia in Parkinson's disease. We evaluated the separate and combined effects of age and severity of extrapyramidal signs on the risk of incident dementia in Parkinson's disease in the setting of a population-based prospective cohort study. Age and the total Unified Parkinson's Disease Rating Scale motor score at baseline evaluation were dichotomized at the median. Four groups of Parkinson's disease patients were defined: younger age/low severity (reference), younger age/high severity, older age/low severity, and older age/high severity. Risk ratios for incident dementia were calculated with Cox proportional hazards models controlling for gender, education, ethnicity, and duration of Parkinson's disease. Of 180 patients, 52 (28.9%) became demented during a mean follow-up period of 3.6 ± 2.2 years. The median age at baseline of the Parkinson's disease patients was 71.8 years (range, 38.5–95.9 years), and the median total Unified Parkinson's Disease Rating Scale motor score was 24 (range, 2–65). The group with older age/high severity had a significantly increased risk of incident dementia (relative risk, 9.7; 95% confidence interval, 3.9–24.4) compared with the group with younger age/low severity (reference), whereas the groups with older age/low severity (relative risk, 1.6; 95% confidence interval, 0.5–4.8) and younger age/high severity (relative risk, 1.2; 95% confidence interval, 0.5–3.2) did not. These findings suggest that the increased risk of incident dementia in Parkinson's disease associated with age and severity of extrapyramidal signs is related primarily to their combined effect rather than separate effects