Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease.

BACKGROUND: The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. METHODS: We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. RESULTS: Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. CONCLUSIONS: Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Evaluating the efficacy of TeleFAMILIES: a telehealth intervention for caregivers of community-dwelling people with dementia.

Examine the efficacy of a telehealth-administered intervention for caregivers of persons with dementia.Two hundred sixteen caregivers engaged in the FAMILIES intervention over six months, either virtually (n = 59) or in-person (n = 157). The telehealth protocol (TeleFAMILIES) was conducted online. Caregivers engaged in six sessions, including individual and family/group counseling, ad hoc counseling, and had access to support groups. Sessions included person-centered assessments of caregivers' physical, emotional, social needs, and current support networks. Primary outcome variables were change in total score between baseline and completion on the Zarit Burden Interview (ZBI), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R), and the Revised Memory and Behavior Problems Checklist (RMBPC).TeleFAMILIES caregivers reported significant reductions in ZBI (p = .002) and CESD-R scores (p < .001). RMBPC reaction scores significantly improved (p = .02) and improved more than in-person caregivers' scores (F (3, 119) = 2.71, p = .048, partial eta2 = .06). For those classified as having a higher risk of depression at baseline, a significantly larger portion TeleFAMILIES caregivers converted to a classification of lower depression risk at completion (p = .02).Compared to the in-person group, TeleFAMILIES caregivers experienced the same, if not greater improvements in perceived burden, depressive symptomatology, and their ability to manage their reactions to behavioral symptoms of dementia. The strengths of TeleFAMILIES are the convenience of telehealth services and its mitigation of barriers to care.

FAMILIES: an effective healthcare intervention for caregivers of community dwelling people living with dementia.

Objectives: Caregiving for a person with dementia (PWD) carries increased risk of poorer health and quality of life. Non-pharmacological interventions improve outcomes for caregivers of PWDs. We evaluated the efficacy of a modified New York University Caregiver Intervention (NYUCI), named FAMILIES, delivered to spousal and non-spousal caregivers of PWDs from diverse etiologies in a reduced number of sessions.Methods: Participants were 122 primary caregivers for community dwelling PWDs in Virginia. The intervention included two individual and four family/group counseling sessions that integrated dementia education, coping skills and behavioral management training, emotional support, and identification of family and community resources. Assessment of depression, caregiver well-being and burden, and caregiver reactions to the behavioral symptoms of dementia (BSD) were completed at baseline, the sixth session, and 6-month follow-up.Results: Symptoms of depression (p < .001) and caregiver burden (p = .001) and caregivers' capacity to effectively manage their reactions to BSD (p = .003), significantly improved at the sixth session. Benefits were maintained at 6-month follow-up. Being married and female predicted improvement in caregiver burden; being male and living in a rural area predicted reduced risk of depression. Caregivers reported that the intervention was helpful and had a positive impact on the PWD.Conclusions: Modifications to the NYUCI did not diminish its efficacy. Caregivers in FAMILIES experienced improvements in depressive symptoms, caregiver burden, and their ability to effectively manage their reactions to BSD. Systemic support for implementing FAMILIES could have a broad impact on caregivers, PWDs, and the healthcare system.

Lower volume, more impairment: reduced cholinergic basal forebrain grey matter density is associated with impaired cognition in Parkinson disease.

OBJECTIVE: A major contributor to dementia in Parkinson disease (PD) is degeneration of the cholinergic basal forebrain. This study determined whether cholinergic nucleus 4 (Ch4) density is associated with cognition in early and more advanced PD. METHODS: We analysed brain MRIs and neuropsychological test scores for 228 newly diagnosed PD participants from the Parkinson's Progression Markers Initiative (PPMI), 101 healthy controls from the PPMI and 125 more advanced PD patients from a local retrospective cohort. Cholinergic basal forebrain nuclei densities were determined by applying probabilistic maps to MPRAGE T1 sequences processed using voxel-based morphometry methods. Relationships between grey matter densities and cognitive scores were analysed using correlations and linear regression models. RESULTS: In more advanced PD, greater Ch4 density was associated with Montreal Cognitive Assessment (MoCA) score (ß=14.2; 95% CI=1.5 to 27.0; p=0.03), attention domain z-score (ß=3.2; 95% CI=0.8 to 5.5; p=0.008) and visuospatial domain z-score (ß=7.9; 95% CI=2.0 to 13.8; p=0.009). In the PPMI PD cohort, higher Ch4 was associated with higher scores on MoCA (ß=9.2; 95% CI=1.9 to 16.5; p=0.01), Judgement of Line Orientation (ß=20.4; 95% CI=13.8 to 27.0; p<0.001), Letter Number Sequencing (ß=16.5; 95% CI=9.5 to 23.4; p<0.001) and Symbol Digit Modalities Test (ß=41.8; 95% CI=18.7 to 65.0; p<0.001). These same relationships were observed in 97 PPMI PD participants at 4 years. There were no significant associations between Ch4 density and cognitive outcomes in healthy controls. CONCLUSION: In de novo and more advanced PD, lower Ch4 density is associated with impaired global cognition, attention and visuospatial function.

Selection of Normative Group Affects Rates of Mild Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: The objective of this study was to examine the impact of different methods of standardizing cognitive data in the Parkinson's Progression Marker Initiative. METHODS: Cognitive data from 423 participants with Parkinson's disease were included (age = 61.7 [9.7], education = 15.6 [3.0]). Internal norms were calculated using the group mean and standard deviation of the healthy control group. Published norms were compared to the overall group mean of and to age-stratified norms from healthy controls for each neuropsychological test over 4 visits. Rates of mild cognitive impairment were calculated using established criteria. RESULTS: The use of internal norms resulted in lower standardized scores than published norms on all tests with the exception of memory and processing speed (P ≤ .001). Individuals were 1.5 to 2.1 times more likely to be diagnosed with mild cognitive impairment using internal norms than published norms. CONCLUSIONS: Standardization approaches with cognitive data are not interchangeable. Selection of a normative comparison group impacts research and clinical interpretations of cognitive data. © 2018 International Parkinson and Movement Disorder Society.

Capgras Syndrome in Advanced Parkinson's Disease.

Psychosis is common in Parkinson's disease (PD), especially in advanced disease, and can lead to a number of psychotic symptoms, including delusions. One uncommon delusion is Capgras syndrome (CS). The authors report on three PD patients with a history of deep brain stimulation (DBS) who developed this delusion. The anatomic targets in these three patients were the subthalamic nuclei in two patients and the globus pallidus interna in one patient. The length of time between surgery and development of CS varied but was greater than 6 months. Additionally, all three patients showed evidence of impaired cognition prior to development of CS. Therefore, due to the length of time between DBS and CS in all three cases and the fact that one patient developed CS months after DBS explanation, DBS does not appear to be associated with CS. Given the distressing nature of this condition, patients with advanced PD who undergo DBS should be regularly screened for symptoms of psychosis with awareness of CS as a potential form.

Subjective Memory Change, Mood, and Cerebrovascular Risk Factors in Older African Americans.

OBJECTIVE: Subjective memory change (SMC) in older individuals may represent a harbinger of cognitive decline. This study examined the factors associated with SMC in older African Americans (AA), who have greater risk of developing dementia. We predicted that symptoms of depression and anxiety, as well as the total number of cerebrovascular risk factors (tCVRFs), but not performances on objective memory measures, would be positively associated with SMC. METHODS: Ninety-six AA completed brief cognitive testing and answered questions about mood and memory at their primary care appointment. Vascular data were obtained from medical records. RESULTS: Symptoms of depression and anxiety, but not performances on objective memory measures, were positively associated with SMC, t(χ2(1) = 16.55 and 12.94, respectively, both P < .001). In nondepressed participants, the tCVRF was important in distinguishing between those with and without SMC. CONCLUSIONS: In older AA, symptoms of depression or anxiety were associated with SMC. In nondepressed AA, the tCVRFs were important in distinguishing between those with and without SMC.

Diagnostic Accuracy and Confidence in the Clinical Detection of Cognitive Impairment in Early-Stage Parkinson Disease.

BACKGROUND/AIMS: Mild cognitive impairment (MCI) is present in up to 34% of patients with early-stage Parkinson disease (PD); however, it is difficult to detect subtle impairment without objective cognitive testing. METHODS: Data were obtained from the Parkinson Progression Marker Initiative. All 341 participants were administered the Montreal Cognitive Assessment (MoCA) and a brief neuropsychological battery. Participants were classified as PD-MCI if MoCA was <26 or if they scored ≥1 standard deviation below the normative mean in 2 or more domains, based upon established criteria. The sensitivity/specificity for the clinical detection of PD-MCI was determined. RESULTS: Overall accuracy for clinical detection of PD-MCI was 67.4%. Although clinical determination was highly specific (96.3%; 95% confidence interval [CI]: 0.92-0.98), sensitivity was poor (32.0%; 95% CI: 0.25-0.40). CONCLUSION: Identifying MCI in early-stage PD based on clinical interview alone appears to be insufficient. The inclusion of objective cognitive tests allowing for normative sample comparisons is needed to increase the detection of cognitive impairment in this population.

Blood Pressure Variability and Cognitive Function Among Older African Americans: Introducing a New Blood Pressure Variability Measure.

BACKGROUND: Although blood pressure (BP) variability has been reported to be associated with cognitive impairment, whether this relationship affects African Americans has been unclear. We sought correlations between systolic and diastolic BP variability and cognitive function in community-dwelling older African Americans, and introduced a new BP variability measure that can be applied to BP data collected in clinical practice. METHODS: We assessed cognitive function in 94 cognitively normal older African Americans using the Mini-Mental State Examination (MMSE) and the Computer Assessment of Mild Cognitive Impairment (CAMCI). We used BP measurements taken at the patients' three most recent primary care clinic visits to generate three traditional BP variability indices, range, standard deviation, and coefficient of variation, plus a new index, random slope, which accounts for unequal BP measurement intervals within and across patients. RESULTS: MMSE scores did not correlate with any of the BP variability indices. Patients with greater diastolic BP variability were less accurate on the CAMCI verbal memory and incidental memory tasks. Results were similar across the four BP variability indices. CONCLUSIONS: In a sample of cognitively intact older African American adults, BP variability did not correlate with global cognitive function, as measured by the MMSE. However, higher diastolic BP variability correlated with poorer verbal and incidental memory. By accounting for differences in BP measurement intervals, our new BP variability index may help alert primary care physicians to patients at particular risk for cognitive decline.

A pilot study of focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor. METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability). RESULTS: Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001). CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

A survey of neuropsychological assessment feedback practices among neuropsychologists.

OBJECTIVE: Feedback on neuropsychological assessment is a critical part of clinical practice, but there are few empirical papers on neuropsychological feedback practices. We sought to fill this gap in the literature by surveying practicing neuropsychologists in the United States. Questions addressed how they provide verbal and written feedback to patients and referral sources. Survey questions also addressed billing practices and training in the provision of feedback. METHODS: A survey was developed using Qualtrics XM to survey currently licensed, independently practicing clinical neuropsychologists in the United States about their feedback practices. The survey was completed by 184 individuals. RESULTS: Nearly all respondents reported that they provide verbal feedback to patients, most often in-person, within three weeks following testing. Typically, verbal feedback sessions with patients last 45 min. Verbal feedback was provided to referrals by about half of our sample, typically via a brief phone call. Most participants also reported providing written feedback to both the patient and referring provider, most commonly via the written report within three weeks after testing. Regarding billing, most respondents use neuropsychological testing evaluation codes. The COVID-19 pandemic appeared to have had a limited impact on the perceived effectiveness and quality of verbal feedback sessions. Finally, respondents reported that across major stages of professional development, training in the provision of feedback gradually increased but was considered inadequate by many participants. CONCLUSIONS: Results provide an empirical summary of the "state of current practice" for providing neuropsychological assessment feedback. Further experimental research is needed to develop an evidence-base for effective feedback practices.

Tele-Neuropsychology: From Science to Policy to Practice.

OBJECTIVE: The primary aim of this paper is to accelerate the number of randomized experimental studies of the reliability and validity in-home tele-neuropsychological testing (tele-np-t). METHOD: We conducted a critical review of the tele-neuropsychology literature. We discuss this research in the context of the United States' public and private healthcare payer systems, including the Centers for Medicare & Medicaid Services (CMS) and Current Procedural Terminology (CPT) coding system's telehealth lists, and existing disparities in healthcare access. RESULTS: The number of tele-np publications has been stagnant since the onset of the COVID-19 pandemic. There are less published experimental studies of tele-neuropsychology (tele-np), and particularly in-home tele-np-t, than other tele-np publications. There is strong foundational evidence of the acceptability, feasibility, and reliability of tele-np-t, but relatively few studies of the reliability and validity of in-home tele-np-t using randomization methodology. CONCLUSIONS: More studies of the reliability and validity of in-home tele-np-t using randomization methodology are necessary to support inclusion of tele-np-t codes on the CMS and CPT telehealth lists, and subsequently, the integration and delivery of in-home tele-np-t services across providers and institutions. These actions are needed to maintain equitable reimbursement of in-home tele-np-t services and address the widespread disparities in healthcare access.

Integrating Lifestyle Factor Science into Neuropsychological Practice: A National Academy of Neuropsychology Education Paper.

OBJECTIVE: The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets. METHOD: We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services. RESULTS: There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning. CONCLUSIONS: Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions.

Depression differentially affects patient and caregiver perceptions of neuropsychiatric symptoms in Parkinson's disease.

OBJECTIVE: The aims of this study were twofold. First, we examined the relationship between patient and caregiver ratings of neuropsychiatric symptoms in Parkinson's disease (PD). Second, we examined if the severity of depressive symptoms affects patient and caregiver perceptions of other neuropsychiatric symptoms and contributes to discrepancies between their perceptions. METHOD: We examined data from a retrospective clinical cohort of 209 patients with PD and their caregivers. We used intra-class correlation coefficients and the Bland Altman method to assess intra-respondent (retrospective versus current) and inter-respondent (patient versus caregiver) agreement between Frontal Systems Behavior Scales (FrSBe) subscale scores. We then used generalized estimating equation models to examine FrSBe subscale scores and the magnitude of the intra- and inter-respondent discrepancies in FrSBe subscale scores, as a function of Beck Depression Inventory-2nd Edition scores, with patient demographic variable adjustments. RESULTS: There was low agreement between patient and caregiver ratings on all three subscales, at both time points, and high response variability within and between raters. Patients generally reported more severe neuropsychiatric symptoms than caregivers. Depression severity predicted patients' perceptions at both time points, but was more strongly associated with current perceptions. Depression severity predicted caregivers' current perceptions only. The inter-respondent discrepancy in perceived apathy and disinhibition, but not executive dysfunction, increased as a function of depression severity. CONCLUSIONS: There are differences in how patients with PD and caregivers perceive neuropsychiatric behaviors and the extent to which depressive symptoms influence their perceptions. Shared neuropathology and negative response biases likely contribute to these relationships.

Cholinergic nucleus 4 grey matter density is associated with apathy in Parkinson's disease.

Objective: The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson's disease (PD). Method: We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Results: Ch4 GMD (p = .021) and Ch123 GMD (p = .032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Conclusions: Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy.

Establishing a framework for quality of inpatient care for Parkinson's disease: A study on inpatient medication administration.

BACKGROUND: The complexity of antiparkinsonian medications makes patients vulnerable to medication deviations. This study examines the frequency and outcomes of deviations between outpatient and inpatient medication administrations in patients with Parkinson's disease (PD). METHODS: We included hospital admissions of patients with PD during a 12-month period at the Cleveland Clinic Main and Fairview campuses. Outpatient regimens were compared with hospital medication administration records to establish rates of deviations in terms of levodopa equivalent daily dose (LEDD) difference, timing deviations/omissions of time-critical medications, substitution of levodopa compounds, and administration of antidopaminergic medications. Logistic regression analyses were used to investigate associations with length of stay (LOS), readmission rates, and mortality. RESULTS: The study included 492 patients with 725 admissions. Of those on time-critical medications, 43% had a LEDD deviation and 19% had levodopa formulation substitutions. Of the admission days with known outpatient timing regimens, 47% had an average deviation of more than 30 min and 22% had at least one missed levodopa dose. LOS was longer with each additional day of over-dose (4%), under-dose (14%), missed dose (21%), timing deviation (15%) and substitution (19%), (all p < 0.0001). Administration of antidopaminergic medications (9.9% of admissions) was associated with increased 30-day readmission/death (OR 1.85, p = 0.041), 90-day mortality (OR 2.2, p = 0.018), and LOS (7.6 vs. 3.8 days, p < 0.0001). LEDD underdose was associated with 30-day readmission/death (OR 1.78, p = 0.025) and 90-day mortality (OR 1.14, CI 1.05-1.24, p = 0.002). CONCLUSIONS: Deviations between outpatient and hospital regimens, and administration of antidopaminergic medications, were associated with poor outcomes.

What makes for a competitive fellowship candidate? A survey of clinical neuropsychology postdoctoral training directors.

To obtain objective data about the factors that clinical neuropsychology postdoctoral training directors (TDs) look for and prioritize in their review and selection of fellowship candidates.We identified 167 TDs who were overseeing postdoctoral training programs that provided training consistent with the Houston Conference Guidelines. We invited all TDs to complete an anonymous online survey that assessed their expectations as they relate to the selection of fellowship candidates. Eighty-eight TDs completed the survey in full. We used descriptive statistics to analyze the data and investigate potential between-group differences in TDs' responses across patient populations, training settings, and APPCN member program status.TDs ranked the intensity of candidates' neuropsychology education and training experiences, their fellowship interviews, and letters of recommendation as most important. Increasing the representation of under-represented minorities and other factors were ranked lower. Minimum benchmarks related to candidates' scholarly productivity, dissertation progress, and the time they spent engaged in clinical neuropsychology activities during internship were revealed. There were relatively few differences in TDs' responses when compared across patient populations, training settings, or APPCN member program status.Students may increase their competitiveness for clinical neuropsychology fellowships by obtaining intensive education and training experiences in the specialty, which includes clinical training and coursework, and by producing scholarly work. Students may also benefit from improving their interviewing skills, completing an internship with at least 40% of time spent in neuropsychological activities, and at minimum by having their dissertation data collected before their fellowship interviews.

Factor structure of the BDI-II in Parkinson's disease.

OBJECTIVE: There is substantial heterogeneity in depressive symptomology for individuals with Parkinson's disease (PD). It is unknown whether the Beck Depression Inventory-Second Edition (BDI-II) is capable of identifying such phenotypic variations of depression. METHOD: We investigated the factor structure of the BDI-II and its associations with demographic characteristics and other nonmotor symptoms in PD. We reviewed the cases of 236 patients with a confirmed PD diagnosis. Evaluations included the BDI-II, Montreal Cognitive Assessment (MoCA), Apathy Scale (AS), and Geriatric Anxiety Inventory (GAI). We used exploratory structural equation modeling (ESEM) with target rotations as this method integrates aspects of exploratory and confirmatory factor analysis. We conducted hierarchical regressions to assess for associations between the BDI-II factors and gender, age, education, disease duration, cognition, anxiety, and apathy. RESULTS: ESEM supported the retention of a Somatic factor and an Affective factor that accounted for 53% of the model variance. Model goodness-of-fit measures were within normal limits. Higher AS scores were positively associated with the Somatic and Affective factors. Higher GAI scores were positively associated only with the Affective factor. There were no other significant relationships with factor scores. CONCLUSIONS: This study supports the retention of a two-factor model of the BDI-II in PD. These unique clusters of depressive symptoms in PD can be used to guide clinical decisions about the need for further psychiatric evaluation and the appropriateness of different therapeutic interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cholinergic nucleus 4 atrophy and gait impairment in Parkinson's disease.

BACKGROUND: There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed. OBJECTIVES: The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients. METHODS: We investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex. RESULTS: Reduced Ch4 GMD was associated with reduced Fast Walking Speed in the "on" medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the "on" medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021). CONCLUSIONS: Reduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD.