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.

Progression of Alzheimer's Disease by Self-Reported Cancer History in the Alzheimer's Disease Neuroimaging Initiative.

BACKGROUND: Cross-sectional studies suggest self-reported cancer history is associated with decreased risk of Alzheimer's disease (AD). However, little is known about how self-reported cancer affects longitudinal AD progression, the primary outcome in clinical trials and observational studies. OBJECTIVE: To determine self-reported cancer history's effect on longitudinal AD progression in an observational study. METHODS: We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to evaluate progression to AD by self-reported all-cancer, breast, prostate, colorectal, or non-melanoma skin cancer history. Linear mixed effects models were used to examine baseline differences and rates of progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) by self-reported cancer history. Age at AD onset was examined using consensus clinical diagnoses with Cox proportional hazards regression. RESULTS: Among 1,271 participants, models revealed no significant differences in progression over time but did reveal significantly lower baseline ADAS-Cog score, indicating better cognition at a given age in those with self-reported cancer history. Cox models indicated those with self-reported cancer history had significantly later age of AD onset (HR: 0.67, 95% CI: 0.53-0.85) after adjustment for covariates. CONCLUSION: Participants with self-reported cancer history entered ADNI with better cognition and later age of AD onset, but progressed similarly to participants without such history, indicating differences in AD between those with and without self-reported cancer history emerge early in the disease course. Such differences in longitudinal progression by self-reported cancer history could affect AD trials and observational studies, given the current focus on early disease course. Further investigation is warranted with detailed longitudinal assessment of cancer and AD.

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.

Interventions for Cognitive Deficits in Breast Cancer Survivors Treated With Chemotherapy.

BACKGROUND: Cognitive deficits are distressing adverse effects of chemotherapy that have a negative effect on quality of life in breast cancer survivors (BCSs). Cognitive deficits in cancer survivors are a top research and clinical practice priority. OBJECTIVE: The aims of this study were to describe cognitive deficits that occur after chemotherapy, describe deficits in BCSs treated with chemotherapy within a framework of cognitive reserve and neuroplasticity, and discuss cognitive interventions (ie, cognitive training interventions, compensatory strategies with cognitive training interventions, pharmacological interventions, and complementary and integrative medicine interventions). METHODS: PubMed search yielded 21 intervention studies of cognitive deficits in BCSs. RESULTS: Cognitive training interventions and compensatory strategies with cognitive training resulted in improvement of cognitive deficits. Methylphenidate did not result in cognitive improvement. Modafinil showed improvement in attention. Some complementary and integrative medicine interventions are promising. CONCLUSIONS: Cognitive training has been most beneficial. Effectiveness of pharmacologic and complementary and integrative medicine interventions has not yet been established. IMPLICATIONS FOR PRACTICE: While limited evidence is available to guide clinical management of cognitive deficits in BCSs, validating patients' symptom experience and evaluating co-occurring symptom clusters such as fatigue, sleep, and depression, are suggested.

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

Cognitive Predictors of Reasoning through Treatment Decisions in Patients with Newly Diagnosed Brain Metastases.

To examine the association between reasoning through medical treatment decisions and cognition in a sample of patients with brain metastasis. The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (i.e., intact or impaired). Results indicate that measures of episodic memory and processing speed were associated with reasoning. Using these two predictors, actuarial equations were constructed that can be used to help screen for impaired reasoning ability in patients' with brain metastasis. The equations presented in this study have clinical significance as they can be used to help identify patients at risk for possessing a diminished ability to reason through medical treatment decisions and, thus, are in need of a more comprehensive evaluation of their medical decision-making capacity.

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.

Cognitive predictors of understanding treatment decisions in patients with newly diagnosed brain metastasis.

BACKGROUND: Medical decision-making capacity is a higher-order functional skill that refers to a patient's ability to make informed, sound decisions related to care and treatment. In a medical context, understanding is the most cognitively demanding consent standard and refers to a patient's ability to comprehend information to the extent that informed decisions can be made. METHODS: The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board-certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (ie, intact or impaired). RESULTS: Results indicate that measures of simple attention, verbal fluency, verbal memory, processing speed, and executive functioning were all associated with understanding, and that verbal memory and phonemic fluency were the primary cognitive predictors. Using these two primary predictors, equations can be constructed to predict the ability to understand treatment decisions in patients with brain metastasis. CONCLUSIONS: Although preliminary, these data demonstrate how cognitive measures can estimate understanding as it relates to medical decision-making capacities in these patients. Clinically, these findings suggest that poor verbal memory and expressive language function could serve as "red flags" for reduced consent capacity in this patient population, thus signaling that a more comprehensive medical decision-making capacity evaluation is warranted.

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.

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.