Sublethal effects of parasitism on ruminants can have cascading consequences for ecosystems.

Parasitic infections are common, but how they shape ecosystem-level processes is understudied. Using a mathematical model and meta-analysis, we explored the potential for helminth parasites to trigger trophic cascades through lethal and sublethal effects imposed on herbivorous ruminant hosts after infection. First, using the model, we linked negative effects of parasitic infection on host survival, fecundity, and feeding rate to host and producer biomass. Our model, parameterized with data from a well-documented producer­caribou­helminth system, reveals that even moderate impacts of parasites on host survival, fecundity, or feeding rate can have cascading effects on ruminant host and producer biomass. Second, using meta-analysis, we investigated the links between helminth infections and traits of free-living ruminant hosts in nature. We found that helminth infections tend to exert negative but sublethal effects on ruminant hosts. Specifically, infection significantly reduces host feeding rates, body mass, and body condition but has weak and highly variable effects on survival and fecundity. Together, these findings suggest that while helminth parasites can trigger trophic cascades through multiple mechanisms, overlooked sublethal effects on nonreproductive traits likely dominate their impacts on ecosystems. In particular, by reducing ruminant herbivory, pervasive helminth infections may contribute to a greener world.

An Autopsy Series of Seven Cases of VPS13A Disease (Chorea-Acanthocytosis).

BACKGROUND: Vacuolar protein sorting 13 homolog A (VPS13A) disease, historically known as chorea-acanthocytosis, is a rare neurodegenerative disorder caused by biallelic mutations in VPS13A, usually resulting in reduced or absent levels of its protein product, VPS13A. VPS13A localizes to contact sites between subcellular organelles, consistent with its recently identified role in lipid transfer between membranes. Mutations are associated with neuronal loss in the striatum, most prominently in the caudate nucleus, and associated marked astrogliosis. There are no other known disease-specific cellular changes (eg, protein aggregation), but autopsy reports to date have been limited, often lacking genetic or biochemical diagnostic confirmation. OBJECTIVE: The goal of this study was to characterize neuropathological findings in the brains of seven patients with VPS13A disease (chorea-acanthocytosis). METHODS: In this study, we collected brain tissues and clinical data from seven cases of VPS13A for neuropathological analysis. The clinical diagnosis was confirmed by the presence of VPS13A mutations and/or immunoblot showing the loss or reduction of VPS13A protein. Tissues underwent routine, special, and immunohistochemical staining focused on neurodegeneration. Electron microscopy was performed in one case. RESULTS: Gross examination showed severe striatal atrophy. Microscopically, there was neuronal loss and astrogliosis in affected regions. Luxol fast blue staining showed variable lipid accumulation with diverse morphology, which was further characterized by electron microscopy. In some cases, rare degenerating p62- and ubiquitin-positive cells were present in affected regions. Calcifications were present in four cases, being extensive in one. CONCLUSIONS: We present the largest autopsy series of biochemically and genetically confirmed VPS13A disease and identify novel histopathological findings implicating abnormal lipid accumulation. © 2023 International Parkinson and Movement Disorder Society.

Sphingolipid and Phospholipid Levels Are Altered in Human Brain in Chorea-Acanthocytosis.

BACKGROUND: Chorea-acanthocytosis (ChAc) is associated with mutations of VPS13A, which encodes for chorein, a protein implicated in lipid transport at intracellular membrane contact sites. OBJECTIVES: The goal of this study was to establish the lipidomic profile of patients with ChAc. METHODS: We analyzed 593 lipid species in the caudate nucleus (CN), putamen, and dorsolateral prefrontal cortex (DLPFC) from postmortem tissues of four patients with ChAc and six patients without ChAc. RESULTS: We found increased levels of bis(monoacylglycerol)phosphate, sulfatide, lysophosphatidylserine, and phosphatidylcholine ether in the CN and putamen, but not in the DLPFC, of patients with ChAc. Phosphatidylserine and monoacylglycerol were increased in the CN and N-acyl phosphatidylserine in the putamen. N-acyl serine was decreased in the CN and DLPFC, whereas lysophosphatidylinositol was decreased in the DLPFC. CONCLUSIONS: We present the first evidence of altered sphingolipid and phospholipid levels in the brains of patients with ChAc. Our observations are congruent with recent findings in cellular and animal models, and implicate defects of lipid processing in VPS13A disease pathophysiology. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

An efficient single-cell transcriptomics workflow for microbial eukaryotes benchmarked on Giardia intestinalis cells.

BACKGROUND: Most diversity in the eukaryotic tree of life is represented by microbial eukaryotes, which is a polyphyletic group also referred to as protists. Among the protists, currently sequenced genomes and transcriptomes give a biased view of the actual diversity. This biased view is partly caused by the scientific community, which has prioritized certain microbes of biomedical and agricultural importance. Additionally, some protists remain difficult to maintain in cultures, which further influences what has been studied. It is now possible to bypass the time-consuming process of cultivation and directly analyze the gene content of single protist cells. Single-cell genomics was used in the first experiments where individual protists cells were genomically explored. Unfortunately, single-cell genomics for protists is often associated with low genome recovery and the assembly process can be complicated because of repetitive intergenic regions. Sequencing repetitive sequences can be avoided if single-cell transcriptomics is used, which only targets the part of the genome that is transcribed. RESULTS: In this study we test different modifications of Smart-seq2, a single-cell RNA sequencing protocol originally developed for mammalian cells, to establish a robust and more cost-efficient workflow for protists. The diplomonad Giardia intestinalis was used in all experiments and the available genome for this species allowed us to benchmark our results. We could observe increased transcript recovery when freeze-thaw cycles were added as an extra step to the Smart-seq2 protocol. Further we reduced the reaction volume and purified the amplified cDNA with alternative beads to test different cost-reducing changes of Smart-seq2. Neither improved the procedure, and reducing the volumes by half led to significantly fewer genes detected. We also added a 5' biotin modification to our primers and reduced the concentration of oligo-dT, to potentially reduce generation of artifacts. Except adding freeze-thaw cycles and reducing the volume, no other modifications lead to a significant change in gene detection. Therefore, we suggest adding freeze-thaw cycles to Smart-seq2 when working with protists and further consider our other modification described to improve cost and time-efficiency. CONCLUSIONS: The presented single-cell RNA sequencing workflow represents an efficient method to explore the diversity and cell biology of individual protist cells.

Biallelic variants in two complex I genes cause abnormal splicing defects in probands with mild Leigh syndrome.

Leigh syndrome is a genetically heterogeneous disorder resulting from deficient oxidative energy biogenesis. The syndrome is characterized by subacute episodic decompensations, transiently elevated lactate, and necrotizing brain lesions most often in the striatum and brainstem. Acute decompensation is often triggered by viral infections. Sequalae from repeated episodes leads to progressive neurological deterioration and death. The severity of Leigh syndrome varies widely, from a rapid demise in childhood to rare adult presentations. Although the causes of Leigh syndrome include genes affecting a variety of different pathways, more than 75 of them are nuclear or mitochondrial encoded genes involved in the assembly and catalytic activity of mitochondrial respiratory complex I. Here we report the detailed clinical and molecular phenotype of two adults with mild presentations of NDUFS3 and NDUFAF6-related Leigh Syndrome. Mitochondrial assays revealed slightly reduced complex I activity in one proband and normal complex I activity in the other. The proband with NDUFS3-related Leigh syndrome was mildly affected and lived into adulthood with novel biallelic variants causing aberrant mRNA splicing (NM_004551.2:c.419G > A; p.Arg140Gln; NM_004551.2:c.381 + 6 T > C). The proband with NDUFAF6-related Leigh syndrome had biallelic variants that cause defects in mRNA splicing (NM_152416.3:c.371 T > C; p.Ile124Thr; NM_152416.3:c.420 + 2_420 + 3insTA). The mild phenotypes of these two individuals may be attributed to some residual production of normal NDUFS3 and NDUFAF6 proteins by NDUFS3 and NDUFAF6 mRNA isoforms alongside mutant transcripts. Taken together, these cases reported herein suggest that splice-regulatory variants to complex I proteins could result in milder phenotypes.

Microbial succession from a subsequent secondary death event following mass mortality.

BACKGROUND: Each death event can be characterized by its associated microbes - a living community of bacteria composed of carcass, soil, and insect-introduced bacterial species - a necrobiome. With the possibility for close succession of these death events, it may be beneficial to characterize how the magnitude of an initial death event may impact the decomposition and necrobiomes of subsequent death events in close proximity. In this paper we hope to characterize the microbial communities associated with a proximate subsequent death event, and distinguish any changes within those communities based on the magnitude of an initial death event and the biomass of preexisting carcass (es) undergoing decomposition. For this experiment, 6 feral swine carcasses in containers were placed in the vicinity of preexisting and ongoing carcass decomposition at sites of three different scales of decomposing carcass biomass. Swab samples were collected from the skin and eye sockets of the container pigs and subjected to 16 s rRNA sequencing and OTU assignment. RESULTS: PERMANOVA analysis of the bacterial taxa showed that there was no significant difference in the bacterial communities based on initial mortality event biomass size, but we did see a change in the bacterial communities over time, and slight differences between the skin and ocular cavity communities. Even without soil input, necrobiome communities can change rapidly. Further characterization of the bacterial necrobiome included utilization of the Random Forest algorithm to identify the most important predictors for time of decomposition. Sample sets were also scanned for notable human and swine-associated pathogens. CONCLUSIONS: The applications from this study are many, ranging from establishing the environmental impacts of mass mortality events to understanding the importance of scavenger, and scavenger microbial community input on decomposition.

Warmer nights offer no respite for a defensive mutualism.

Ecologically relevant symbioses are widespread in terrestrial arthropods but based on recent findings these specialized interactions are likely to be especially vulnerable to climate warming. Importantly, empirical data and climate models indicate that warming is occurring asynchronously, with night-time temperatures increasing faster than daytime temperatures. Daytime (DTW) and night-time warming (NTW) may impact ectothermic animals and their interactions differently as DTW results in greater daily temperature variation and moves organisms nearer to their thermal limits, while NTW avoids thermal limits and may relieve constraints of cooler night-time temperatures; a nuance that has largely been ignored in the literature. In laboratory experiments, we investigated how the timing of warming influences a widespread defensive mutualism involving the pea aphid Acyrthosiphon pisum, and its heritable symbiont, Hamiltonella defensa, which protects against an important natural enemy, the parasitic wasp Aphidius ervi. Three aphid sublines were experimentally created from single aphid genotype susceptible to A. ervi: one line infected with a highly protective H. defensa strain, one infected with a moderately protective strain and one without any facultative symbiont. We examined aphid fitness in the presence and absence of parasitoids and when exposed to an average 2.5°C increase occurring across three warming scenarios (night-time vs. daytime vs. uniform) relative to no-warming controls. An increase of 2.5°C, as predicted to occur by the IPCC before 2100, was sufficient to disable the aphid defensive mutualism regardless of the timing of warming; a surprising result given that the daily maxima for control and NTW scenarios were identical. We also found that warming negatively impacted (a) symbiont-mediated interactions between host and parasitoid more than symbiont-free ones; (b) species interactions (host-parasitoid) more than each participant independently and (c) aphids more than parasitoids even though higher trophic levels are generally predicted to be more affected by warming. Here we show that 2.5°C warming, regardless of timing, negatively impacted a common microbe-mediated defensive mutualism. While this was a laboratory-based study, results suggest that temperature increases predicted in the near-term may disrupt the many ecological symbioses present in terrestrial ecosystems.

Opposite effects of daytime and nighttime warming on top-down control of plant diversity.

Ecological analyses of climate warming explore how rising mean temperature will affect the species composition of communities and their associated functioning. Experimentation usually presumes that warming arises from simultaneous increase in daily maximum (daytime) and minimum (nighttime) temperatures. Yet evidence shows that mean warming arises largely from increasing nighttime temperatures. We report on a 3-yr experiment that compared the effects of daytime and nighttime warming on a community comprising herbaceous plants, grasshopper herbivores and predatory spiders. We warmed experimental mesocosms 3-4°C above ambient control treatments during the daytime (06:00-18:00 h) or nighttime (18:00-06:00 h). Daytime warming caused spiders to seek a thermal refuge low in the plant canopy and away from grasshopper prey, which allowed grasshoppers to spend more time feeding on a competitively dominant plant species. Nighttime had the opposite effect, where spider activity increased causing grasshoppers to reduce feeding. Two consecutive years of daytime warming resulted in a suppression of the competitive dominant plant and increased the diversity and evenness of the plant community, whereas nighttime warming had opposite effects. These results show that ignoring the nuanced effects of asymmetrical warming may lead to inaccurate conclusions about the net effects of climate change on ecosystems.

Covariance between predation risk and nutritional preferences confounds interpretations of giving-up density experiments.

Giving-up density (GUD) experiments have been a foundational method to evaluate perceived predation risk, but rely on the assumption that food preferences are absolute, so that areas with higher GUDs can be interpreted as having higher risk. However, nutritional preferences are context dependent and can change with risk. We used spiders and grasshoppers to test the hypothesis that covariance in nutritional preferences and risk may confound the interpretation of GUD experiments. We presented grasshoppers with carbohydrate-rich and protein-rich diets, in the presence and absence of spider predators. Predators reduced grasshopper preference for the protein-rich food, but increased their preference for the carbohydrate-rich food. We then measured GUDs with both food types under different levels of risk (spider density, 0-5). As expected, GUDs increased with spider density indicating increasing risk, but only when using protein-rich food. With carbohydrate-rich food, GUD was independent of predation risk. Our results demonstrate that predation risk and nutritional preferences covary and can confound interpretation of GUD experiments.

International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease.

OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD). BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016. METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported. RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful. CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

Why and How to Create Nighttime Warming Treatments for Ecological Field Experiments.

While average global temperatures are increasing, a disproportionate amount of warming can be attributed to increasing nighttime temperatures rather than increasing daytime temperatures. Theory predicts that the timing of warming can generate different effects on organisms and their interactions within ecosystems. This occurs because an organism's response to warming depends on the current temperature. For example, warming when temperatures are low may have positive effects on an organism, while warming when temperatures are already high may have negative effects on an organism. Most field experiments that examine the ecological effects of climate warming employ warming methodologies that disproportionately elevate daytime warming treatments. The bias towards daytime warming treatments may arise because daytime temperatures can be manipulated with relatively simple and inexpensive technology that capitalizes on solar energy, such as open-top chambers that create a "greenhouse effect" or shade structures that reduce temperatures. However, these popular methods are ineffective when solar radiation is absent, and thus do not create warming treatments that accurately mimic the temporal patterns of climate warming. To encourage the investigation of nighttime warming's effect on ecosystems, we discuss why daytime and nighttime warming may have different effects on organisms, then present a review of methods that can be employed to elevate nighttime temperature in terrestrial field experiments. For each method, we offer a brief explanation, an evaluation of its pros and cons, and citations for further reference, as well as empirical data when possible. While some are impractical, we attempt to provide a comprehensive list of potential nighttime warming methods in hopes of stimulating ideas and discussions.

Combined effects of night warming and light pollution on predator-prey interactions.

Interactions between multiple anthropogenic environmental changes can drive non-additive effects in ecological systems, and the non-additive effects can in turn be amplified or dampened by spatial covariation among environmental changes. We investigated the combined effects of night-time warming and light pollution on pea aphids and two predatory ladybeetle species. As expected, neither night-time warming nor light pollution changed the suppression of aphids by the ladybeetle species that forages effectively in darkness. However, for the more-visual predator, warming and light had non-additive effects in which together they caused much lower aphid abundances. These results are particularly relevant for agriculture near urban areas that experience both light pollution and warming from urban heat islands. Because warming and light pollution can have non-additive effects, predicting their possible combined consequences over broad spatial scales requires knowing how they co-occur. We found that night-time temperature change since 1949 covaried positively with light pollution, which has the potential to increase their non-additive effects on pea aphid control by 70% in US alfalfa. Our results highlight the importance of non-additive effects of multiple environmental factors on species and food webs, especially when these factors co-occur.

The body size dependence of trophic cascades.

Trophic cascades are indirect positive effects of predators on resources via control of intermediate consumers. Larger-bodied predators appear to induce stronger trophic cascades (a greater rebound of resource density toward carrying capacity), but how this happens is unknown because we lack a clear depiction of how the strength of trophic cascades is determined. Using consumer resource models, we first show that the strength of a trophic cascade has an upper limit set by the interaction strength between the basal trophic group and its consumer and that this limit is approached as the interaction strength between the consumer and its predator increases. We then express the strength of a trophic cascade explicitly in terms of predator body size and use two independent parameter sets to calculate how the strength of a trophic cascade depends on predator size. Both parameter sets predict a positive effect of predator size on the strength of a trophic cascade, driven mostly by the body size dependence of the interaction strength between the first two trophic levels. Our results support previous empirical findings and suggest that the loss of larger predators will have greater consequences on trophic control and biomass structure in food webs than the loss of smaller predators.

A bioenergetic framework for the temperature dependence of trophic interactions.

Changing temperature can substantially shift ecological communities by altering the strength and stability of trophic interactions. Because many ecological rates are constrained by temperature, new approaches are required to understand how simultaneous changes in multiple rates alter the relative performance of species and their trophic interactions. We develop an energetic approach to identify the relationship between biomass fluxes and standing biomass across trophic levels. Our approach links ecological rates and trophic dynamics to measure temperature-dependent changes to the strength of trophic interactions and determine how these changes alter food web stability. It accomplishes this by using biomass as a common energetic currency and isolating three temperature-dependent processes that are common to all consumer-resource interactions: biomass accumulation of the resource, resource consumption and consumer mortality. Using this framework, we clarify when and how temperature alters consumer to resource biomass ratios, equilibrium resilience, consumer variability, extinction risk and transient vs. equilibrium dynamics. Finally, we characterise key asymmetries in species responses to temperature that produce these distinct dynamic behaviours and identify when they are likely to emerge. Overall, our framework provides a mechanistic and more unified understanding of the temperature dependence of trophic dynamics in terms of ecological rates, biomass ratios and stability.

Direct and indirect effects of warming on aphids, their predators, and ant mutualists.

Species exist within communities of other interacting species, so an exogenous force that directly affects one species can indirectly affect all other members of the community. In the case of climate change, many species may be affected directly and subsequently initiate numerous indirect effects that propagate throughout the community. Therefore, the net effect of climate change on any one species is a function of the direct and indirect effects. We investigated the direct and indirect effects of climate warming on corn leaf aphids, a pest of corn and other grasses, by performing an experimental manipulation of temperature, predators, and two common aphid-tending ants. Although warming had a positive direct effect on aphid population growth rate, warming reduced aphid abundance when ants and predators were present. This occurred because winter ants, which aggressively defend aphids from predators under control temperatures, were less aggressive toward predators and less abundant when temperatures were increased. In contrast, warming increased the abundance of cornfield ants, but they did not protect aphids from predators with the same vigor as winter ants. Thus, warming broke down the ant-aphid mutualism and counterintuitively reduced the abundance of this agricultural pest.

Species interactions and a chain of indirect effects driven by reduced precipitation.

Climate change can affect species directly and indirectly by altering interactions between species within communities. These indirect effects can ramify through a community and affect many species, including some that may not have been directly affected by the perturbation. Identifying these chains of indirect effects is difficult, and most studies only follow indirect effects across two or three species. Here, we use a factorial field experiment to demonstrate that precipitation affects spotted aphids through a complex chain of indirect interactions that are mediated by other herbivores and a generalist predator. We experimentally simulated drought, which reduced water content in alfalfa plants. While water stress in alfalfa had no direct effect on spotted aphids, it lowered the population growth rate of pea aphids, another common alfalfa pest. Because ladybeetle predators were attracted to high pea aphid densities, predator densities were lower in drought treatments. Consequently, spotted aphid densities were released from top-down control (apparent competition) in drought treatments and reached densities three times higher than spotted aphids in ambient treatments with high pea aphid densities. Thus, drought affected spotted aphids in the interaction chain: drought --> alfalfa --> pea aphids --> predators --> spotted aphids. This result illustrates the lengthy path that indirect effects of climate change may take through a community, as well as the importance of community-level experiments in determining the net effect of climate change.

Comparison of the Movement Disorder Society Parkinson's disease dementia criteria with neuropsychological testing.

The objective of our study was to compare Movement Disorder Society Task Force criteria for diagnosis of Parkinson's disease dementia (PDD) with the gold standard of traditional neuropsychological testing. A short checklist (Level I) and a protocol of neuropsychological tests (Level II) have been proposed by a Movement Disorder Society Task Force but not fully validated in clinical practice. Ninety-one Parkinson's disease (PD) subjects were categorized as having dementia or no dementia based on a battery of neuropsychological test results and clinical judgment. The isolated components needed for Level I and Level II diagnoses were then culled from the neuropsychological evaluations and independently used to designate PDD. Compared with traditional neuropsychological testing, the sensitivity and specificity of Level I criteria for PDD was 66.7% and 98.8%, and for Level II criteria 100% and 92.7%, respectively. Using Level II criteria, 6 additional subjects were diagnosed with PDD that were classified as having no dementia when full neuropsychological data were used for the diagnosis. These 6 subjects had more education years and were less impaired on cognitive tests. The Movement Disorder Society's Level II criteria more frequently classify subjects with PDD than does traditional neuropsychological testing. Whereas Level II criteria may overclassify subjects as having PDD, they are very accurate in ruling out dementia. Movement Disorder Society's criteria are practical and timesaving, although full neuropsychological testing may still be needed.

Cost of deep brain stimulation for the treatment of Parkinson's disease by surgical stimulation sites.

OBJECTIVE: To assess costs and effectiveness of deep brain stimulation (DBS) of the internal globus pallidum (GPi) versus subthalamic nucleus (STN) from the provider and societal perspectives for Parkinson's disease (PD) patients in a multicenter randomized trial. METHODS: All costs from randomization to 36 months were included. Costs were from Department of Veterans Affairs (VA) and Medicare databases and clinical trial data. Quality adjusted life years (QALYs) were from Quality of Well Being questionnaires. RESULTS: Provider costs were similar for the 144 GPi and 130 STN patients (GPi: $138,044 vs. STN: $131,822; difference = $6,222, 95% confidence interval [CI]: -$42,125 to $45,343). Societal costs were also similar (GPi: $171,061 vs. STN: $167,706; difference = $3,356, 95% CI: -$57,371 to $60,294). The GPi patients had nonsignificantly more QALYs. CONCLUSIONS: The QALYs and costs were similar; the level of uncertainty given the sample size suggests that these factors should not direct treatment or resource allocation decisions in selecting or making available either procedure for eligible PD patients.

Clinical validation of Movement Disorder Society-recommended diagnostic criteria for Parkinson's disease with dementia.

The objective of this work was to evaluate the Movement Disorders Society (MDS) Task Force-proposed screening checklist for detecting Parkinson's disease dementia (PD-D) in relation to full neuropsychological testing. An MDS Task Force has proposed diagnostic procedures for PD-D, which have not been fully validated against more extensive neuropsychological testing. PD subjects were recruited from 2 specialty centers. A neuropsychologist evaluated them for dementia as part of routine clinical care. Independent clinical neurologists administered the MDS PD-D screening checklist. Diagnosis of PD-D by the 2 methods was compared. Ninety-one PD subjects had a mean age of 66.3 (SD = 9.7) years and a mean PD duration of 8.8 (SD = 6.1) years. Seven subjects (7.7%) met all 8 screening checklist criteria from the MDS PD-D screening tool and were classified as probable PD-D. Fifteen (16.5%) subjects were classified as PD-D by full neuropsychological assessment. The screening checklist showed 100% specificity, but only 46.7% sensitivity, for diagnosing PD-D compared to the full neuropsychological assessment. PD-D cases missed by the PD-D screening tool were largely due to 2 checklist items that were not endorsed (absence of depression and Mini-Mental State Examination [MMSE] scores <26). There was moderate agreement between these 2 methods for determination of PD-D (kappa = 0.59, P < .001). The MDS-PD-D screening checklist is highly accurate for detecting PD-D if all items are endorsed. However, for cases that do not meet these criteria, full neuropsychological testing is needed to differentiate PD-D from milder cognitive impairment. Revision of the checklist by altering or eliminating the 2 problematic checklist items may improve sensitivity.