Jacob D. Jones

Coordinate-Based Lead Location Does Not Predict Parkinson's Disease Deep Brain Stimulation Outcome

Background Effective target regions for deep brain stimulation (DBS) in Parkinsons disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone. Methods 55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinsons Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes. Results Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082). Conclusion The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.

The late positive potential, emotion and apathy in Parkinson’s disease

Parkinsons disease is associated with emotional changes including depression, apathy, and anxiety. The current study investigated emotional processing in non-demented individuals with Parkinson disease (PD) using an electrophysiological measure, the centro-parietal late positive potential (LPP). Non-demented patients with Parkinsons disease (n=17) and healthy control participants (n=16) viewed pleasant, neutral, and unpleasant pictures while EEG was recorded from a 64-channel geodesic net. The Parkinson patients did not differ from controls in terms of early electrophysiological components that index perceptual processing (occipital P100, N150, P250). Parkinson patients, however, showed reduced LPP amplitude specifically when viewing unpleasant, compared to pleasant, pictures as well as when compared to controls, consistent with previous studies suggesting a specific difference in aversive processing between PD patients and healthy controls. Importantly, LPP amplitude during unpleasant picture viewing was most attenuated for patients reporting high apathy. The data suggest that apathy in PD may be related to a deficit in defensive activation, and may be indexed cortically using event-related potentials.

Anxiety and Depression Are Better Correlates of Parkinson’s Disease Quality of Life Than Apathy

Due to controversy regarding the influence of apathy on quality of life (QoL), the authors examined the independent influence of apathy, depression, and trait anxiety in a nondemented sample of patients with Parkinson disease (PD). Participants (N=107) completed standard self-report measures of QoL and mood/motivation. Analyses investigated the contribution of these measures and empirically derived factor scores on QoL. QoL was predicted by trait anxiety, dysphoria, and decreased interest, with no independent contribution of apathy. Different patterns emerged with respect to domain-specific QoL, with trait anxiety being the strongest predictor across most domains. Anxiety was most widely related to QoL in PD, with minimal contribution of apathy. Future studies should examine different roles of PD mood/motivation symptoms on caregiver QoL.

Health comorbidities and cognition in 1948 patients with idiopathic Parkinson's disease.

BACKGROUND Health comorbidities, particularly cardiovascular factors, are well known to pose risks for cognitive decline in older adults. This study examined the prevalence and contribution of comorbidities on cognitive performance in a large cohort of Parkinson patients. METHODS Data on 1948 PD patients were obtained from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry, a multi-site initiative from NPF Centers of Excellence. Available comorbidity data included six common conditions (heart/circulation problems, diabetes, arthritis, cancer, respiratory disease, and other neurologic disease) that were clinician-rated for presence and severity. Available cognitive measures included semantic fluency and a 5-word recall memory task. The unique effects of comorbidities on cognition were analyzed (multiple hierarchical regression) controlling for demographic, PD disease severity (duration, Hoehn-Yahr), and medication status. RESULTS The two most reported comorbidities were arthritis (46.6%) and heart/circulation problems (36.3%), with diabetes affecting 9% of the sample. Severity of heart/circulation problems independently contributed to worse delayed recall performance (p = 0.03). A trend emerged for more severe diabetes as contributing to worse semantic fluency scores (p = 0.06). CONCLUSIONS This study with a large cohort of PD patients provides evidence for a small detrimental influence of specific health comorbidities, particularly heart/circulatory and diabetes, on general measures of cognition. This effect is present, above and beyond the influences of basic demographic information (age), duration and staging of PD, and medication status. Future studies involving more refined cognitive indices and direct assessment of comorbidities are warranted.

Influence of Hypertension on Neurocognitive Domains in Nondemented Parkinson’s Disease Patients

Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinsons disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinsons Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus in 81 participants ranging in age from 24 to 76 including 59 HIV+ individuals and 22 HIV‐seronegative controls. T1‐weighted MRI underwent a preprocessing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum, and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus, and thalamus. Of greatest interest, an age × HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age × HIV interaction. These findings may suggest that age and HIV infection conferred additional deleterious effects on subcortical shape abnormalities beyond the independent effects of these factors. Hum Brain Mapp 38:1025–1037, 2017.

Selection of Deep Brain Stimulation Candidates in Private Neurology Practices: Referral May Be Simpler than a Computerized Triage System

Objective:  The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard.

Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV- adults.

BACKGROUND The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. METHODS Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e.,<20 copies/mL), and all were on a stable regimen of cART. RESULTS For HIV+ and HIV- participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV- controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43g per week, the HIV- group displayed significantly better neurocognitive performance than the HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there were no significant HIV group differences in global cognitive performance (t=1.39, p=0.168). CONCLUSIONS Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV- MJ users.

Latent growth-curve analysis reveals that worsening Parkinson's disease quality of life is driven by depression.

OBJECTIVE Parkinsons disease (PD) is a neurodegenerative disorder resulting in a wide variety of symptoms. The current study examined the influence of apathy, depression and motor symptoms on quality of life (QoL) in PD patients. Information was drawn from an 18-month period. METHOD Participants (N = 397) were assessed for apathy (Apathy Scale; Starkstein et al., 1992), depression (Beck Depression Inventory-II; Beck, Steer, Ball & Ranieri, 1996), motor severity (Unified Parkinsons Disease Rating Scale, Part III; UPDRS; Fahn, Elton & Committee, 1987), and QoL (Parkinsons Disease Questionnaire-39; Jenkinson, Fitzpatrick, Peto, Greenhall, & Hyman,1997) at 3 time points: an initial clinical evaluation (baseline), a 6-month follow-up, and an 18-month follow-up. Latent growth-curve models were used to determine the influence of apathy, depression, and motor symptoms on QoL trajectories. RESULTS Greater difficulties with QoL at baseline showed the strongest relationship to more severe depression symptoms, followed by more severe motor symptoms, younger age, and less education (all p values < .001). Worsening of QoL over the 18-month period was only predicted by a worsening of depression (p = .003). The relationship between QoL and depression symptoms remained significant in a subsample of nondepressed PD patients. CONCLUSION Overall, findings from the current study suggest that self-reported QoL among PD patients is primarily related to depression. Future efforts to improving clinical care of PD patients may benefit by focusing on improving psychosocial adjustment or treatments targeting depression.

Cognitive declines after deep brain stimulation are likely to be attributable to more than caudate penetration and lead location.

Sir, We have read the follow-up paper from the German multi-centre randomized deep brain stimulation (DBS) trial (Witt et al. , 2013) with great interest. The authors conducted a study investigating the relationship between DBS lead trajectory and cognitive decline after surgery performed in patients with Parkinson’s disease. They concluded that penetration of the caudate nucleus was a risk factor for global cognitive decline, and that suboptimal placement of the electrode outside of the subthalamic nucleus (STN) also increased the risk of verbal fluency decline. These were interesting findings, however, we strongly suspect that these two issues make up only a subset of what is likely multiple factors affecting DBS cognitive outcome. The pathophysiology of cognitive decline in Parkinson’s disease is complex, and cognitive decline after STN DBS may be affected by baseline cognitive dysfunction, brain atrophy, and by surgical complications (e.g. intracranial haemorrhage). To more closely examine this issue, …