Prognostic predictors relevant to end-of-life palliative care in Parkinson's disease and related disorders: a systematic review.

Parkinson's disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970-2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson's Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD.

Using diffusion of innovations framework to examine the dissemination and implementation of the adult protective services national voluntary consensus guidelines.

The National Voluntary Consensus Guidelines for Adult Protective Services (APS) were released in 2016 by the Administration for Community Living. These Guidelines help standardize systems to ensure the protection of older adults and adults with disabilities against abuse, neglect, and financial exploitation. Since their release, the extent to which state APS programs are aware of and using the Guidelines is unknown. This study examined the dissemination and implementation of the Guidelines across APS programs in the US. Researchers used the Diffusion of Innovations Theory to develop a survey sent to APS directors in all states. Forty-two states responded, and results were used to select a subset of states in which to conduct in-depth interviews. Awareness of the Guidelines was widespread but varied. Reported use of the Guidelines indicates that states are working to incorporate them into their practices. Respondents identified the need for more research and training in evidence-based practices.

Building the adult protective services system of tomorrow: The role of the APS national voluntary consensus guidelines.

In 2015, the Administration for Community Living (ACL) established the first federal "home" for Adult Protective Services (APS). This leadership has included working collaboratively with state Adult Protective Service systems to ensure that older adults and adults with disabilities are afforded the same protections against abuse, neglect, and financial exploitation regardless of where in the country they live. As part of that leadership, ACL created draft Voluntary Consensus Guidelines for State APS Systems. ACL undertook a process of public and stakeholder engagement and analyzed the resulting comments to improve upon the initial draft of the draft to arrive at the final version. This article examines the comments, including the concerns raised by the commenters about specific areas of the Guidelines, areas identified for future research, and reflections and opinions on the role of the federal government in guiding the development of the field of adult protection.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers.

BACKGROUND: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. CONCLUSIONS: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

Directed evolution of a formate dehydrogenase for increased tolerance to ionic liquids reveals a new site for increasing the stability.

The formate dehydrogenase (FDH) from Candida boidinii is a well-known enzyme in biocatalysis for NADH regeneration. Nevertheless, it has low activity in a water-miscible ionic liquid (1,3-dimethylimidazolium dimethyl phosphate, [MMIm][Me2 PO4 ]). In this work, this enzyme was subjected to directed evolution by using error-prone PCR, and a mutant (N187S/T321S) displaying higher activity was obtained following selection based on the formazan-based colorimetric assay. The mutation N187S is responsible for improved activity both in aqueous solution and in [MMIm][Me2 PO4 ], through an enhancement of the kcat value by a factor of 5.8. Fluorescence experiments performed in the presence of a quenching agent revealed that the mutant does not unfold in the presence of 50 % (v/v) [MMIm][Me2 PO4 ] whereas the wild-type enzyme does. Molecular modelling revealed that the mutation is located at the monomer-monomer interface and causes an increase in the pKa of residue E163 from 4.8 to 5.5. Calculation of the pKa of this residue in other microbial FDHs showed that thermostable FDHs have a highly basic glutamate at this position (pKa up to 6.2). We have identified a new site for improving FDH thermostability and tolerance to ionic liquids, and it is linked to the local charge of the enzymes in this class.

Evaluation of Kilifi epilepsy education programme: a randomized controlled trial.

OBJECTIVES: The epilepsy treatment gap is largest in resource-poor countries. We evaluated the efficacy of a 1-day health education program in a rural area of Kenya. The primary outcome was adherence to antiepileptic drugs (AEDs) as measured by drug levels in the blood, and the secondary outcomes were seizure frequency and Kilifi Epilepsy Beliefs and Attitudes Scores (KEBAS). METHODS: Seven hundred thirty-eight people with epilepsy (PWE) and their designated supporter were randomized to either the intervention (education) or nonintervention group. Data were collected at baseline and 1 year after the education intervention was administered to the intervention group. There were 581 PWE assessed at both time points. At the end of the study, 105 PWE from the intervention group and 86 from the nonintervention group gave blood samples, which were assayed for the most commonly used AEDs (phenobarbital, phenytoin, and carbamazepine). The proportions of PWE with detectable AED levels were determined using a standard blood assay method. The laboratory technicians conducting the assays were blinded to the randomization. Secondary outcomes were evaluated using questionnaires administered by trained field staff. Modified Poisson regression was used to investigate the factors associated with improved adherence (transition from nonoptimal AED level in blood at baseline to optimal levels at follow-up), reduced seizures, and improved KEBAS, which was done as a post hoc analysis. This trial is registered in ISRCTN register under ISRCTN35680481. RESULTS: There was no significant difference in adherence to AEDs based on detectable drug levels (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 0.74-2.90, p = 0.28) or by self-reports (OR 1.00, 95% CI 0.71-1.40, p = 1.00) between the intervention and nonintervention group. The intervention group had significantly fewer beliefs about traditional causes of epilepsy, cultural treatment, and negative stereotypes than the nonintervention group. There was no difference in seizure frequency. A comparison of the baseline and follow-up data showed a significant increase in adherence-intervention group (36-81% [p < 0.001]) and nonintervention group (38-74% [p < 0.001])-using detectable blood levels. The number of patients with less frequent seizures (≤3 seizures in the last 3 months) increased in the intervention group (62-80% [p = 0.002]) and in the nonintervention group (67-75% [p = 0.04]). Improved therapeutic adherence (observed in both groups combined) was positively associated with positive change in beliefs about risks of epilepsy (relative risk [RR] 2.00, 95% CI 1.03-3.95) and having nontraditional religious beliefs (RR 2.01, 95% CI 1.01-3.99). Reduced seizure frequency was associated with improved adherence (RR 1.72, 95% CI 1.19-2.47). Positive changes in KEBAS were associated with having tertiary education as compared to none (RR 1.09, 95% CI 1.05-1.14). SIGNIFICANCE: Health education improves knowledge about epilepsy, but once only contact does not improve adherence. However, sustained education may improve adherence in future studies.

Evaluating the Dyadic Benefits of Early-Phase Behavioral Interventions: An Exemplar Using Data From Couples Living With Parkinson's Disease.

BACKGROUND AND OBJECTIVES: There are a growing number of early-phase (i.e., Stage I, NIH Stage Model) interventions targeted at family care dyads navigating chronic health conditions in older adults. Currently, the benefits of these interventions are often evaluated for older adults and their family care partners separately, even when controlling for interdependence. Without understanding the benefits (and potential harms) for dyads as a whole, understanding of program impact is incomplete. Moreover, few health behavior interventions involving dyads include relational measures to ensure no unintended consequences for the dyad or account for within-dyad pretest risk level. RESEARCH DESIGN AND METHODS: We used secondary data from a quasi-experimental trial involving 39 couples in which 1 member of the dyad was living with Parkinson's disease as an exemplar demonstration of 3 proposed approaches: an above-zero approach, a pretest risk status approach, and an expanded pattern analysis matrix approach. RESULTS: Approaches provided evidence for dyadic benefits of the intervention compared to the wait-list comparison condition, but carried different assumptions that did not always categorize dyads similarly. DISCUSSION AND IMPLICATIONS: Implications of using each approach and selecting different benchmarks for defining success are discussed. The descriptive approaches proposed, provide a rationale for more intentional evaluation of small-sample, early-phase dyadic interventions.

Geographic destiny trumps taxonomy in the Roundtail Chub, Gila robusta species complex (Teleostei, Leuciscidae).

The Gila robusta species complex in the lower reaches of the Colorado River includes three nominal and contested species (G. robusta, G. intermedia, and G. nigra) originally defined by morphological and meristic characters. In subsequent investigations, none of these characters proved diagnostic, and species assignments were based on capture location. Two recent studies applied conservation genomics to assess species boundaries and reached contrasting conclusions: an ezRAD phylogenetic study resolved 5 lineages with poor alignment to species categories and proposed a single species with multiple population partitions. In contrast, a dd-RAD coalescent study concluded that the three nominal species are well-supported evolutionarily lineages. Here we developed a draft genome (~ 1.229 Gbp) to apply genome-wide coverage (10,246 SNPs) with nearly range-wide sampling of specimens (G. robusta N = 266, G. intermedia N = 241, and G. nigra N = 117) to resolve this debate. All three nominal species were polyphyletic, whereas 5 of 8 watersheds were monophyletic. AMOVA partitioned 23.1% of genetic variance among nominal species, 30.9% among watersheds, and the Little Colorado River was highly distinct (FST ranged from 0.79 to 0.88 across analyses). Likewise, DAPC identified watersheds as more distinct than species, with the Little Colorado River having 297 fixed nucleotide differences compared to zero fixed differences among the three nominal species. In every analysis, geography explains more of the observed variance than putative taxonomy, and there are no diagnostic molecular or morphological characters to justify species designation. Our analysis reconciles previous work by showing that species identities based on type location are supported by significant divergence, but natural geographic partitions show consistently greater divergence. Thus, our data confirm Gila robusta as a single polytypic species with roughly a dozen highly isolated geographic populations, providing a strong scientific basis for watershed-based future conservation.

Development and validation of the Kilifi Stigma Scale for Epilepsy in Kenya.

The aim of this study was to develop and validate a tool to measure perceived stigma among people with epilepsy (PWE) in Kilifi, Kenya. We reviewed existing scales that measured stigma, particularly of epilepsy. We conducted a qualitative study to determine salient concerns related to stigma in Kilifi. Themes were generated, and those related to stigma were used to construct an 18-item stigma scale. A descriptive cross-sectional survey was then conducted among 673 PWE to assess the reliability and validity of the scale. Internal consistency was calculated using Cronbach's alpha and test-retest reliability with an interclass correlation coefficient. The final scale had 15 items, which had high internal consistency (Cronbach's α=0.91) and excellent test-retest reliability (r=0.92). Factor analysis indicated that the scale was unidimensional with one factor solution explaining 45.8% of the variance. The Kilifi Stigma Scale for Epilepsy is a culturally appropriate measure of stigma with strong psychometric properties.

Development and validation of the Kilifi Epilepsy Beliefs and Attitude Scale.

Epilepsy remains misunderstood, particularly in resource poor countries (RPC). We developed and validated a tool to assess beliefs and attitudes about epilepsy among people with epilepsy (PWE) in Kilifi, Kenya. The 50-item scale was developed through a literature review and qualitative study findings, and its reliability and validity were assessed with 673 PWE. A final scale of 34 items had Cronbach's alpha scores for the five subscales: causes of epilepsy (α=0.71); biomedical treatment of epilepsy (α=0.70); cultural treatment of epilepsy (α=0.75); risk and safety concerns about epilepsy (α=0.56); and negative attitudes about epilepsy (α=0.76) and entire scale (α=0.70). Test-retest reliability was acceptable for all the subscales. The Kilifi Epilepsy Beliefs and Attitude Scale is a reliable and valid tool that measures beliefs and attitudes about epilepsy. It may be useful in other RPC or as a tool to assess the effectiveness of interventions to improve knowledge, beliefs, and attitudes about epilepsy.

The reasons for the epilepsy treatment gap in Kilifi, Kenya: using formative research to identify interventions to improve adherence to antiepileptic drugs.

Many people with epilepsy (PWE) in resource-poor countries do not receive appropriate treatment, a phenomenon referred to as the epilepsy treatment gap (ETG). We conducted a qualitative study to explore the reasons for this gap and to identify possible interventions in Kilifi, Kenya. Focus group discussions (FGDs) were carried out of PWE and their caregivers. Individual interviews were conducted of PWE, their caregivers, traditional healers, community health workers and leaders, nurses and doctors. In addition, a series of workshops was conducted, and four factors contributing to the ETG were identified: 1) lack of knowledge about the causes, treatment and prognosis of epilepsy; 2) inaccessibility to antiepileptic drugs; 3) misconceptions about epilepsy derived from superstitions about its origin; 4) and dissatisfaction with the communication skills of health providers. These data indicated possible interventions: 1) education and support for PWE and their caregivers; 2) communication skills training for health providers; 3) and improved drug provision.

Telehealth rehabilitation for adults with cochlear implants in response to the Covid-19 pandemic: platform selection and case studies.

BACKGROUND: Effective information giving and goal setting before cochlear implantation and individualised rehabilitation following implantation are both crucial for shaping patients' expectations and optimising outcomes. The Covid-19 pandemic led to temporary cessation of face to face clinic appointments. This created a need for telehealth rehabilitation for adults whose hearing loss presents unique communication challenges. AIMS: We describe the piloting and implementation of telehealth rehabilitation within an adult cochlear implant service. METHOD: Video conferencing and telehealth tools were assessed in terms of security, accessibility and functionality. Written support materials were developed. Telehealth sessions were piloted with lay volunteers. During service implementation, feedback was collected from patients and staff. OUTCOMES & RESULTS: A video call platform was identified that was supported by the host Trust and also met the rehabilitation service's needs. A telehealth service was successfully implemented, ensuring continuity of care during lockdown. We share the platform selection framework used, practical lessons learned and patient support materials. CONCLUSION: .Telehealth rehabilitation facilitated a well-received, effective service for adult cochlear implant patients. It is predicted that the benefits of telehealth rehabilitation will last beyond the lockdown restrictions posed by Covid-19.

Using wildland fire smoke modeling data in gerontological health research (California, 2007-2018).

Widespread population exposure to wildland fire smoke underscores the urgent need for new techniques to characterize fire-derived pollution for epidemiologic studies and to build climate-resilient communities especially for aging populations. Using atmospheric chemical transport modeling, we examined air quality with and without wildland fire smoke PM2.5. In 12-km gridded output, the 24-hour average concentration of all-source PM2.5 in California (2007-2018) was 5.16 µg/m3 (S.D. 4.66 µg/m3). The average concentration of fire-PM2.5 in California by year was 1.61 µg/m3 (~30% of total PM2.5). The contribution of fire-source PM2.5 ranged from 6.8% to 49%. We define a "smokewave" as two or more consecutive days with modeled levels above 35 µg/m3. Based on model-derived fire-PM2.5, 99.5% of California's population lived in a county that experienced at least one smokewave from 2007 to 2018, yet understanding of the impact of smoke on the health of aging populations is limited. Approximately 2.7 million (56%) of California residents aged 65+ years lived in counties representing the top 3 quartiles of fire-PM2.5 concentrations (2007-2018). For each year (2007-2018), grid cells containing skilled nursing facilities had significantly higher mean concentrations of all-source PM2.5 than cells without those facilities, but they also had generally lower mean concentrations of wildland fire-specific PM2.5. Compared to rural monitors in California, model predictions of wildland fire impacts on daily average PM2.5 carbon (organic and elemental) performed well most years but tended to overestimate wildland fire impacts for high-fire years. The modeling system isolated wildland fire PM2.5 from other sources at monitored and unmonitored locations, which is important for understanding exposures for aging population in health studies.

Benefits of a Self-Management Program for the Couple Living With Parkinson's Disease: A Pilot Study.

The goal of this pilot study was to explore health benefits for couples participating together in an existing community-based self-management workshop for Parkinson's disease (PD). A quasi-experimental two-wave design explored the effects of the Strive to Thrive program in comparison to a wait-list control condition. Preliminary data (n = 39 couples) showed that spouses in the intervention group had greater engagement in mental relaxation techniques at 7 weeks than those in the control condition (large effect size). Small effects were observed for increases in aerobic activity and mental relaxation for the adult with PD, increases in strength-based activities and self-efficacy for spouses, declines in depressive symptoms for spouses, and decreases in protective buffering for both adults with PD and spouses. The program showed potential for existing community-based programs to benefit couples living with chronic illness.

Assessing perceptions and priorities for health impacts of climate change within local Michigan health departments.

Climate change affects Michigan's public health in several primary ways, including increased incidences of vector-borne, waterborne, heat-related, and respiratory illness. Because local health departments (LHDs) play a central role in surveillance and preventative health services, they are among the first institutions to contend with the local impacts of climate change. To assess current perceptions among Michigan public health officials, an online survey was conducted in partnership with the Michigan Association for Local Public Health (MALPH). Most of the Michigan respondents (62%, n = 34) agreed that their jurisdictions have experienced climate change in the last 20 years, and 77% agreed that climate change will impact their jurisdictions in the coming 20 years. However, only 35% (n = 34) of Michigan officials agreed that climate change is a priority in their departments. About one quarter (25%, n = 34) of Michigan LHD respondents did not know about the level of expertise of either the state and federal agencies, responsible for assisting them with information and programs related to climate change and health. Uncertainty regarding the resources available to them may hinder LHDs from developing necessary preparedness, so meeting this need could bolster the public health response to climate change. Supplementary Information: The online version contains supplementary material available at 10.1007/s13412-021-00679-0.

Does age make a difference in caregiver strain? Comparison of young versus older caregivers in early-stage Parkinson's disease.

Family care research has identified negative outcomes of providing care to a spouse with Parkinson's disease (PD), such as declining physical and mental health. Research has also identified protective variables that decrease negative outcomes such as high mutuality and rewards of meaning. It is important for clinicians to identify "at risk" family caregivers and provide earlier interventions. Despite the importance of age and developmental stage there is a paucity of research comparing young versus older spouse caregivers. This study compared the difference in negative aspects of strain and modulators of strain in young and older PD spouse caregivers. A series of hierarchical multiple regressions were used to examine the contribution of age on both positive and negative aspects of the care situation for 65 (37 young, 28 old) PD spouse caregivers. Negative variables included 3 dimensions of strain; strain from lack of personal resources, strain from worry, and global strain. Positive or protective variables included mutuality, preparedness, and rewards of meaning. Even in early stage disease before significant care is required, young spouses (40-55) were found to be at greater risk for negative consequences of the care situation reporting significantly more strain from lack of personal resources, and lower levels of mutuality and rewards of meaning than older (greater than 70) spouses. As expected, young spouses were more likely to be working, caring for children in the home, and in better physical health than older spouses. Clinicians are well-situated to identify the unique needs of young spouses and intervene early in the caregiving trajectory. These findings provide ideas for targeted interventions. Future larger studies that compare young and older spouses should include later stage disease to more fully understand the developmental differences raised by the present findings.

Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage.

BACKGROUND: Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. METHODS: An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition. RESULTS: CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. DISCUSSION: The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory.

Using community/researcher partnerships to develop a culturally relevant intervention for children with communication disabilities in Kenya.

PURPOSE: The objective of this study is to develop a culturally relevant community-based intervention for children with communication disabilities in Kenya through a community/researcher partnership. The resulting intervention is for use in a randomized control trial which will be reported at a later stage. METHOD: Using a qualitative approach, initial data was collected through focus group discussions with women, disabled people and traditional dancers. The groups examined the needs, problems and challenges faced by disabled children and their families. This generated the content and structure for a series of participatory workshops with a further two women's groups. These workshops strove to generate a culturally relevant community-based intervention programme for children with communication disabilities and their families. The content and balance of the resulting intervention was observed to be different from existing programmes described in the literature. Notably it included many culturally appropriate strategies for increasing social integration and raising community awareness. RESULTS: The process of generating a locally relevant community-based rehabilitation intervention is potentially transferable and has particular relevance to the estimated 80% of the world where there are no formal rehabilitation services for children with disabilities and where women's groups are a strong element of local culture. CONCLUSION: (i) Community/researcher partnerships can be used to develop interventions; (ii) such interventions are different from those imported from other cultures; and (iii) this process is transferable and can be part of the preparations for a Randomized Control Trial.

Child development: risk factors for adverse outcomes in developing countries.

Poverty and associated health, nutrition, and social factors prevent at least 200 million children in developing countries from attaining their developmental potential. We review the evidence linking compromised development with modifiable biological and psychosocial risks encountered by children from birth to 5 years of age. We identify four key risk factors where the need for intervention is urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron deficiency anaemia. The evidence is also sufficient to warrant interventions for malaria, intrauterine growth restriction, maternal depression, exposure to violence, and exposure to heavy metals. We discuss the research needed to clarify the effect of other potential risk factors on child development. The prevalence of the risk factors and their effect on development and human potential are substantial. Furthermore, risks often occur together or cumulatively, with concomitant increased adverse effects on the development of the world's poorest children.

Do motor and nonmotor symptoms in PD patients predict caregiver strain and depression?

Our objective was to understand the impact of motor and nonmotor symptoms of patients with early and middle stage Parkinson's disease (PD) on their spouses' caregiver strain and depression. A sample of 219 spouse caregivers of PD patients participating in a clinical trial was evaluated for six dimensions of caregiver strain and depression using the Family Care Inventory. Motor and nonmotor (i.e., psychological) clinical symptoms collected from PD patients as part of the clinical trial protocol were used as predictors. Seven hierarchical regression analyses were used to determine the contribution of the motor and nonmotor clinical symptoms in explaining variation in each of the seven caregiver-dependent variables. Clinical symptoms explained 9-16% of the variance in caregiver strain and 10% of depression. Motor symptoms explained 0-6% of the variance and nonmotor psychological symptoms explained 7-13% of the variance in caregiver strain. Comparing our findings with literature that is deemed clinically relevant for patient symptoms that predict caregiver strain, we concluded that PD patient symptoms are important predictors of caregiver strain and depression. Patient nonmotor psychological symptoms have a much greater impact on caregiver strain and depression than patient motor symptoms.