Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Correlates of deep brain stimulation consensus conference decision to treat primary dystonia.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for motor disturbance in people with primary dystonia (PWD). Numerous factors are considered by an interdisciplinary consensus conference before deciding candidacy for DBS surgery (e.g., demographic, medical, cognitive, and behavioral factors). However, little is known about which of these factors are associated with PWD DBS surgery consensus conference decisions. OBJECTIVE: Our goal was to examine whether pre-operative demographic, medical, and cognitive/behavioral variables are associated DBS consensus conference decisions in patients with dystonia. METHODS: Thirty-two PWD completed comprehensive presurgery workup included neurological and neuropsychological exams, and neuroimaging in consideration for DBS surgery. An interdisciplinary conference committee either recommended or did not recommend DBS surgery based upon these data. Demographic and medical data (e.g., dystonia disease characteristics, medical comorbidities, medications) were also collected. We also examined impact from cardiovascular disease factors, using a Revised Cardiac Risk Index. PWD were grouped based on DBS conference decision (eligible: n = 21, ineligible: n = 11) and compared across demographic, medical, and cognitive/behavioral variables. RESULTS: Across clinical variables, PWD who were deemed ineligible for DBS surgery had a higher Revised Cardiac Risk Index. PWD who were classified as ineligible displayed lower global cognitive functioning, working memory, phonemic fluency, memory retrieval, and cognitive flexibility. CONCLUSIONS: Consensus decision making regarding DBS surgery eligibility involves a multifactorial process. We found that deficits in executive functioning were associated with the DBS consensus committee decision. We also observed elevated cardiac risk among these individuals, likely reflecting the relation between vascular health and cognition. Implications, and clinical and scientific applications of these findings are discussed.

An examination of the neurocognitive profile and base rate of performance impairment in primary dystonia.

BACKGROUND: Primary dystonia has been traditionally viewed as a motor disorder. However, non-motor symptoms are frequently present and significantly quality of life. Neuropsychiatric and cognitive symptoms have been identified, but prior studies have been limited in sample size and lack of control groups. This study examined the neurocognitive profile of a sample of persons with primary dystonia (PWD) as compared to demographically matched healthy control group. METHODS: A cognitive test battery was administered to 25 PWD who presented for pre-surgical candidacy evaluation for deep brain stimulation surgery. The test battery domains included global cognitive function, attention, expressive language, visuospatial skills, memory, and executive functioning. Twenty-five age, gender, education-matched healthy control participants were compared to the PWD. RESULTS: Compared to demographically matched healthy controls, PWD performed worse on measures of global cognitive function, attention, memory, and conceptualization. Based on normative comparison, a large portion of PWD were impaired on tasks of executive functioning and expressive language. Over 80% of the PWD showed impairment on at least one neurocognitive measure and over 60% showed impairment on 3 or more tests. CONCLUSIONS: Neurocognitive deficits were prevalent among our PWD sample. These impairments were present across a broad range of cognitive domains. Given the degree of cognitive impairment found in this study, our results have implications for health care providers with providing interventions to PWD.

Impairment of medical decisional capacity in relation to Karnofsky Performance Status in adults with malignant brain tumor.

BACKGROUND: We aimed to investigate the relationship between medical decisional capacity (MDC) and Karnofsky Performance Status (KPS) in adults with malignant brain tumors. METHODS: Participants were 71 adults with primary (n = 26) or metastatic (n = 45) brain tumors. Testing to determine KPS scores and MDC was performed as close together as possible for each patient. Participants were administered a standardized measure of medical decision-making capacity (Capacity to Consent to Treatment Instrument [CCTI]) to assess 3 treatment consent abilities (ie, appreciation, reasoning, and understanding). Capacity classifications (ie, capable, marginally capable, and incapable) were established using cut scores previously derived from healthy control CCTI performance. RESULTS: The majority of participants had KPS scores of 90-100 (n = 39), with the remainder divided between KPS scores of 70-80 (n = 26) and 50-60 (n = 6). Comparisons between persons with KPS scores of 90-100 or 70-80 revealed significant differences on the CCTI consent standards of understanding and appreciation. Participants with KPS ratings of 90-100 achieved 46% capable classifications across all CCTI standards, in contrast with 23% of participants with KPS ratings of 70-80, and 0% of participants with KPS ratings of 50-60. CONCLUSIONS: A substantial portion of brain-tumor patients with KPS scores reflecting only minimal disability nonetheless demonstrated impairments on standardized measures of MDC. Clinicians working with this adult population should carefully screen for capacity to make clinical treatment decisions regardless of functional/performance status.

Capacity of patients with brain metastases to make treatment decisions.

OBJECTIVE: The aim of this study was to investigate medical decision-making capacity (MDC) in patients with brain metastases. METHODS: Participants were 41 adults with brain metastases with Karnofsky Performance Status scores of ≥70 who were recruited from an academic medical center and 41 demographically matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS: The brain metastasis patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION: When defining capacity compromise as performance ≤1.5 standard deviation below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population.

Cognition in patients with newly diagnosed brain metastasis: profiles and implications.

Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis.

Psychiatric and neurologic risk factors for incident cases of new-onset epilepsy in older adults: data from U.S. Medicare beneficiaries.

OBJECTIVE: Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults. Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans. Our aim was to examine the relationship between these disorders in a population-based study of older adults that also included women and minorities. METHODS: We used a national 5% random sample of 2005 Medicare beneficiaries including all 50 US states and Washington, DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A and Part B coverage and not in managed care plans. Epilepsy cases were identified from claims for physician visits, hospitalizations, and outpatient procedures. We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), adjustment disorder, and substance abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease, dementia, traumatic brain injury, brain tumor, metastatic cancer). RESULTS: Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated. Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy; substance abuse, psychosis, bipolar disorder, schizophrenia, and depression. Gender interaction effects were found for substance abuse/dependence and brain tumors. SIGNIFICANCE: Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population-based sample of male and female older adults. These results support earlier findings and extend the understanding of risk models for new-onset epilepsy in broader older adult populations.

Capacity to consent to research participation in adults with malignant glioma.

PURPOSE: To investigate research consent capacity (RCC) in patients with malignant gliomas (MGs) and identify cognitive abilities and clinical factors associated with RCC in MG. PATIENTS AND METHODS: Participants were 22 healthy controls and 26 patients with diagnosed and histologically verified MG. All patients with MG were receiving various combinations of treatment (surgery, radiation, chemotherapy, medication). Both groups were administered a neurocognitive test battery and a standardized RCC measure (Capacity to Consent to Research Instrument [CCRI]). Capacity performance was evaluated across four core consent abilities (choice, appreciation, reasoning, understanding), and categorical capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) were also identified for individual patients with MG. Stepwise regression analyses identified cognitive predictors of CCRI performance in the MG group. RESULTS: The MG patient group performed significantly below the control group on the three clinically relevant consent standards (appreciation, reasoning, and understanding). Patients with MG performed equivalently to controls in evidencing a simple research participation choice. Approximately one third of patients with MG showed compromised impairment ratings (mild/moderate impairment or severe impairment) on the three consent abilities. Cognitive measures of phonemic and semantic word fluency predicted performance on the consent standards. Steroid treatment and anticonvulsant use were related to poorer CCRI performance. CONCLUSION: A substantial portion of patients with MG after diagnosis show impairments in research consent capacity. Word fluency measures reflecting expressive language and executive function abilities are strongly associated with these consent impairments. This study highlights the importance of careful attention to consent issues when enrolling patients with MG in clinical trials and other research studies.

Medical decision-making capacity in patients with malignant glioma.

OBJECTIVE: Patients with malignant glioma (MG) must make ongoing medical treatment decisions concerning a progressive disease that erodes cognition. We prospectively assessed medical decision-making capacity (MDC) in patients with MG using a standardized psychometric instrument. METHODS: Participants were 22 healthy controls and 26 patients with histologically verified MG. Group performance was compared on the Capacity to Consent to Treatment Instrument (CCTI), a psychometric measure of MDC incorporating 4 standards (choice, understanding, reasoning, and appreciation), and on neuropsychological and demographic variables. Capacity outcomes (capable, marginally capable, or incapable) on the CCTI standards were identified for the MG group. Within the MG group, scores on demographic, clinical, and neuropsychological variables were correlated with scores on each CCTI standard, and significant bivariate correlates were subsequently entered into exploratory stepwise regression analyses to identify multivariate cognitive predictors of the CCTI standards. RESULTS: Patients with MG performed significantly below controls on consent standards of understanding and reasoning, and showed a trend on appreciation. Relative to controls, more than 50% of the patients with MG demonstrated capacity compromise (marginally capable or incapable outcomes) in MDC. In the MG group, cognitive measures of verbal acquisition/recall and, to a lesser extent, semantic fluency predicted performance on the appreciation, reasoning, and understanding standards. Karnofsky score was also associated with CCTI performance. CONCLUSIONS: Soon after diagnosis, patients with malignant glioma (MG) have impaired capacity to make treatment decisions relative to controls. Medical decision-making capacity (MDC) impairment in MG seems to be primarily related to the effects of short-term verbal memory deficits. Ongoing assessment of MDC in patients with MG is strongly recommended.

Confirmatory factor analysis of the california verbal learning test in patients with epilepsy: relationship to clinical and neuropathological markers of temporal lobe epilepsy.

Latent constructs involved in California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) performance were examined using confirmatory factor analysis in 388 epilepsy surgery candidates. Eight factor models were compared. A single-factor model was examined, along with 7 models accommodating constructs of auditory attention, inaccurate recall, and delayed recall in different combinations. The retained model consisted of 3 correlated factors: Auditory Attention. Verbal Learning, and Inaccurate Recall. Validity of this factor structure was examined in a subsample of patients with left and right temporal lobe epilepsy. All 3 factors were related to seizure focus and magnetic resonance imaging hippocampal volume. Only Verbal Learning was related to hippocampal neuropathology, supporting the distinction between learning and attention in the factor structure.