Do changes in beliefs and behaviours moderate improvement in insomnia after acquired brain injury?

Key mechanisms of change in cognitive behavioural therapy for insomnia in the general population encompass changing sleep-related beliefs and behaviours. In a population with acquired brain injury, cognitive behavioural therapy for insomnia is effective as well, but little is known about the mechanisms of change. The aim of this study was to evaluate how changing sleep-related beliefs and behaviours were associated with improvement in insomnia following blended cognitive behavioural therapy for insomnia in a population with acquired brain injury. A secondary analysis was performed on data of a randomized-controlled trial, including 24 participants that received blended cognitive behavioural therapy for insomnia, and 24 participants that received treatment as usual. Results showed that following blended cognitive behavioural therapy for insomnia, significantly more participants improved on dysfunctional beliefs and sleep-related behaviours and this was associated to improvement in insomnia severity. For sleep-related behaviours, the association between improvement on behaviour and improvement on insomnia was significantly moderated by blended cognitive behavioural therapy for insomnia. However, the relation between dysfunctional beliefs and insomnia was not moderated by type of treatment. Similar results were found for acquired brain injury-adapted versions of the questionnaires in which up to half of the items were excluded as they could be regarded as not dysfunctional for people with acquired brain injury. These results show that improvement on insomnia severity is related to improvement in dysfunctional beliefs and behaviours, and cognitive behavioural therapy for insomnia efficacy may be moderated by the improvement in behaviours in particular. A focus on these behaviours can enhance treatment efficacy, but caution is needed regarding the behaviours that may reflect adequate coping with the consequences of the acquired brain injury.

Validity of the Groningen Effort Test in patients with suspected chronic solvent-induced encephalopathy.

INTRODUCTION: The use of performance validity tests (PVTs) in a neuropsychological assessment to determine indications of invalid performance has been a common practice for over a decade. Most PVTs are memory-based; therefore, the Groningen Effort Test (GET), a non-memory-based PVT, has been developed. OBJECTIVES: This study aimed to validate the GET in patients with suspected chronic solvent-induced encephalopathy (CSE) using the criterion standard of 2PVTs. A second goal was to determine diagnostic accuracy for GET. METHOD: Sixty patients with suspected CSE referred for NPA were included. The GET was compared to the criterion standard of 2PVTs based on the Test of Memory Malingering and the Amsterdam Short Term Memory Test. RESULTS: The frequency of invalid performance using the GET was significantly higher compared to the criterion of 2PVTs (51.7% vs. 20.0% respectively; p < 0.001). For the GET index, the sensitivity was 75% and the specificity was 54%, with a Youden's Index of 27. CONCLUSION: The GET showed significantly more invalid performance compared to the 2PVTs criterion suggesting a high number of false positives. The general accepted minimum norm of specificity for PVTs of >90% was not met. Therefore, the GET is of limited use in clinical practice with suspected CSE patients.

Neuropsychological stability in classical galactosemia: A pilot study in 10 adult patients.

Classical galactosemia (CG) is an autosomal recessive disorder of galactose metabolism. Despite early initiation of a galactose-restricted diet, patients develop long-term complications including cognitive impairment. There is an ongoing debate whether the cognitive impairment in CG is stable throughout life or progresses with age. Earlier cross-sectional and longitudinal studies regarding intelligence suggest stability, but longitudinal neuropsychological studies focusing on specific cognitive functions are limited. Therefore, the aim of this study is to assess cognitive change over time in adult CG-patients. Ten adult patients with normal to borderline intelligence (mean age 33 years, range 22-49; IQ≥70 or independent work- or living situation) were assessed twice with a mean time interval of 3 years and 9 months (range 1023-1575 days). The neuropsychological assessments covered information processing speed, executive functioning, verbal fluency, and visuospatial functioning. Results showed that there was no significant decline or improvement in test scores on all neuropsychological measures except a decline on the Trail Making Test-A (p = 0.048). However, this group-level difference was subject to "regression to the mean" and was not endorsed by significant change in test scores measuring the same cognitive domain. Moreover, no specific pattern of reliable change (RCI > -1.96) was present on specific measures or within individual patients. This explorative study performed in 10 adult CG-patients with normal to borderline intelligence revealed no cognitive change on several cognitive domains. This implies that the subset of adults with a normal to borderline IQ in their early and middle adulthood are cognitively stable.

Social cognition, emotion regulation and social competence in classical galactosemia patients without intellectual disability.

OBJECTIVE: Classical galactosemia (CG) is an inborn error of galactose metabolism. Many CG patients suffer from long-term complications including poor cognitive functioning. There are indications of social dysfunction but limited evidence in the literature. Therefore, this study aims to improve our understanding of social competence in CG by investigating social cognition, neurocognition and emotion regulation. METHODS: A comprehensive (neuro)psychological test battery, including self and proxy questionnaires, was administered to CG patients without intellectual disability. Social cognition was assessed by facial emotion recognition, Theory of Mind and self-reported empathy. Standardised results were compared to normative data of the general population. RESULTS: Data from 23 patients (aged 8-52) were included in the study. On a group level, CG patients reported satisfaction with social roles and no social dysfunction despite the self-report of lower social skills. They showed deficits in all aspects of social cognition on both performance tests (emotion recognition and Theory of Mind) and self-report questionnaires (empathy). Adults had a lower social participation than the general population. Parents reported lower social functioning, less adaptive emotion regulation and communication difficulties in their children. Individual differences in scores were present. CONCLUSION: This study shows that CG patients without intellectual disability are satisfied with their social competence, especially social functioning. Nevertheless, deficits in social cognition are present in a large proportion of CG patients. Due to the large variability in scores and discrepancies between self- and proxy-report, an individually tailored, comprehensive neuropsychological assessment including social cognition is advised in all CG patients. Treatment plans need to be customised to the individual patient.

Cognitive and psychiatric outcomes in the GALAXY trial: effect of anaesthesia in deep brain stimulation.

BACKGROUND: This study aims: (1) To compare cognitive and psychiatric outcomes after bilateral awake versus asleep subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD). (2) To explore the occurrence of psychiatric diagnoses, cognitive impairment and quality of life after surgery in our whole sample. (3) To validate whether we can predict postoperative cognitive decline. METHODS: 110 patients with PD were randomised to receive awake (n=56) or asleep (n=54) STN DBS surgery. At baseline and 6-month follow-up, all patients underwent standardised assessments testing several cognitive domains, psychiatric symptoms and quality of life. RESULTS: There were no differences on neuropsychological composite scores and psychiatric symptoms between the groups, but we found small differences on individual tests and cognitive domains. The asleep group performed better on the Rey Auditory Verbal Learning Test delayed memory test (f=4.2, p=0.04), while the awake group improved on the Rivermead Behavioural Memory Test delayed memory test. (f=4.4, p=0.04). The Stroop III score was worse for the awake group (f=5.5, p=0.02). Worse scores were present for Stroop I (Stroop word card) (f=6.3, p=0.01), Stroop II (Stroop color card) (f=46.4, p<0.001), Stroop III (Stroop color-word card) (f=10.8, p=0.001) and Trailmaking B/A (f=4.5, p=0.04). Improvements were seen on quality of life: Parkinson's Disease Questionnaire-39 (f=24.8, p<0.001), and psychiatric scales: Hamilton Depression Rating Scale (f=6.2, p=0.01), and Hamilton Anxiety Rating Scale (f=5.5, p=0.02). CONCLUSIONS: This study suggests that the choice between awake and asleep STN DBS does not affect cognitive, mood and behavioural adverse effects, despite a minor difference in memory. STN DBS has a beneficial effect on quality of life, mood and anxiety symptoms. TRIAL REGISTRATION NUMBER: NTR5809.

Treatments for partial remission of major depressive disorder: a systematic review and meta-analysis.

QUESTION: Partial remission of major depressive disorder (MDD) is a debilitating and distressing clinical state related to chronicity, morbidity and relapse. Although one-third of patients remit partially, evidence for treatment efficacy is unclear. We provide an overview of treatment options and their efficacy. STUDY SELECTION AND ANALYSIS: Embase, PsycINFO, Medline and SCOPUS were systematically searched through February 2023. Included were randomised controlled trials (RCTs) examining any treatment in patients with partially remitted MDD aged 13-65 years, reporting data on severity, remission or relapse. FINDINGS: Seven RCTs examining psychotherapy including 1024 patients were eligible. There were not enough RCTs to examine effects of pharmacotherapy. Psychotherapy was associated with lower depressive symptom severity at post-treatment (Hedges' g=0.50; 95% CI 0.23 to 0.76), but not at follow-up up to 1 year (Hedges' g=0.36; 95% CI -0.30 to 1.02) or longer (Hedges' g=0.02; 95% CI -0.09 to 0.12). Psychotherapy was associated with superior remission rates at post-treatment (OR 2.57; 95% CI 1.71 to 3.87) and follow-up 6 months or longer (OR 1.75; 95% CI 1.21 to 2.53), although not with improved relapse rates at post-treatment (OR 0.17; 95% CI 0.01 to 4.83) or follow-up 6 months or longer (OR 0.46; 95% CI 0.21 to 1.03). Overall methodological quality was poor. CONCLUSIONS: Psychotherapy targeting partial remission may be effective in lowering depressive symptom severity and patients may potentially achieve full remission twice as likely. Yet, long-term and prophylactic effects are lacking. Given the risk of chronicity, more high-quality RCTs are needed. PROSPERO REGISTRATION NUMBER: CRD42020188451.

Are sleep-related beliefs and behaviours dysfunctional in people with insomnia after acquired brain injury? A cross-sectional study.

Inappropriate sleep-related beliefs and behaviours are considered key maladaptive mechanisms in the development and maintenance of insomnia in the otherwise healthy population. The aim of this study was to evaluate critically the role of sleep-related beliefs and behaviours in insomnia after acquired brain injury. Cross-sectional data of 51 outpatients with insomnia disorder and acquired brain injury were used to evaluate associations of the insomnia severity index with the dysfunctional beliefs and attitudes about sleep scale and sleep-related behaviours questionnaire. Seven (44%) of the dysfunctional beliefs and attitudes about sleep scale items and 10 (31%) of the sleep-related behaviours questionnaire items correlated significantly with insomnia severity. Ten experts were consulted on whether they considered the questionnaire items maladaptive or accurately reflecting coping with conditions experienced by people with acquired brain injury. Although multiple linear regression showed that the total scores of the questionnaires explained a significant part of interindividual differences in insomnia severity (R2 = 0.27, F(2,48) = 8.72, p < 0.01), the experts unanimously rated only four (25%) of the dysfunctional beliefs and attitudes about sleep scale items as dysfunctional beliefs and three (9%) of the sleep-related behaviours questionnaire items as safety behaviours. In people with brain injury, sleep related beliefs and behaviours may also play a role in insomnia, especially a diminished perception of control and worry about sleep. However, more than half of the questionnaire items on sleep-related beliefs and behaviours may not be considered inappropriate and maladaptive for the acquired brain injury population, and may reflect adequate observations and efforts in coping with consequences of the brain damage.

The challenges of classical galactosemia: HRQoL in pediatric and adult patients.

BACKGROUND: Classical galactosemia (CG), an inborn error of galactose metabolism, results in long-term complications including cognitive impairment and movement disorders, despite early diagnosis and dietary treatment. Two decades ago, lower motor-, cognitive- and social health related quality of life (HRQoL) was demonstrated in pediatric and adult patients. Since then, the diet has been relaxed, newborn screening was implemented and new international guidelines resulted in major changes in follow-up. The aim of this study was to assess HRQoL of CG by means of online self- and/or proxy-HRQoL-questionnaires focusing on the main areas of concern of CG (i.e. anxiety, depression, cognition, fatigue, social- and upper extremity function) within the patient-reported outcomes measurement information system (PROMIS®) and generic HRQoL-questionnaires (TAPQOL, TACQOL, TAAQOL). RESULTS: Data of 61 Dutch patients (aged 1-52 years) were collected and compared to available Dutch or US reference populations. On the PROMIS-questionnaires, children reported more fatigue (P = 0.044), lower function in upper extremities (P = 0.021), more cognitive difficulties (P = 0.055, d = 0.56) and higher anxiety (P = 0.063, d = 0.52) than reference children although the latter findings remained non-significant. Parents of CG patients reported lower quality of peer relationships of their children (P < 0.001). Both children and parents reported lower cognitive functioning (P = 0.005, P = 0.010) on the TACQOL. Adults reported on PROMIS domains lower cognitive functioning (P = 0.030), higher anxiety (P = 0.004) and more fatigue (P = 0.026). Cognitive difficulties were reported on the TAAQOL by adults (P < 0.001), as well as physical-, sleeping and social difficulties. CONCLUSIONS: CG remains to impact the HRQoL of pediatric and adult patients negatively on several domains including cognition, anxiety, motor function and fatigue. A lower social health was mainly reported by parents, and not by patients themselves. The Covid-19 pandemic might have amplified the results on anxiety although higher levels of anxiety fit pre-pandemic findings. The reported fatigue is a new finding in CG. Because the effect of lockdown fatigue could not be eliminated and fatigue is a frequent finding in patients with chronic disorders, future studies are warranted. Clinicians and researchers should be attentive to both pediatric and adult patients, and the age-dependent difficulties they might encounter.

The Effect of Preoperative Disability, Cognitive Impairment, Frailty and Opioid Use on Acute Postoperative Pain in Older Patients Undergoing Surgery A Prospective Cohort Study.

Globally, life expectancy is increasing, leading to more surgeries being performed in older patients. Postoperative pain is associated with complications after surgery. The aim of this study is to explore potential age-related risk factors for acute postoperative pain in older patients undergoing surgery. This was a prospective, single-center study. Patients ≥65 years, with and without disability, as defined by the WHO Disability Assessment Schedule 2.0, undergoing elective surgery, were compared. Primary outcome was the postoperative pain (ie, numeric rating scale (NRS) score) on the first postoperative day. Secondary outcomes were postoperative pain and pain trajectories in patients with and without mild cognitive impairment (MCI), frailty, preoperative opioid use, and new-onset disability after surgery. Between February 2019 and July 2020, 155 patients were enrolled. On the first day after surgery, postoperative pain did not differ between patients with and without disability. NRS scores differed between patients with-, and without MCI on the first (P = .01), and second postoperative day (P < .01). Patients who used opioids before surgery reported higher median NRS score on the first (P < .001) and second (P < .01) postoperative day. Out of a total of 1816 NRS scores, 2 pain clusters were identified. Acute postoperative pain did not differ between patients with or without preoperative disability and frailty in older patients undergoing surgery. Reduced postoperative pain in older patients with MCI warrants further investigation. The PIANO study (Comparison of Postoperative NeurocognitiveFunction in Older Adult Patients with and without Diabetes Mellitus) was registered with www.clinicaltrialregister.nl (search term: Which can predict memory problems after surgery better; blood sugar levels or memory before surgery?). PERSPECTIVE: This study explored risk factors for acute postoperative pain in older patients. No differences in postoperative pain were observed in patients with or without preexistent disability or frailty, however, patients with mild cognitive impairment experienced reduced pain. We suggest to simplify pain assessment in this group and take functional recovery into account.

Is suboptimal effort an issue? A systematic review on neuropsychological performance validity in major depressive disorder.

BACKGROUND: In Major Depressive Disorder (MDD), emotion- and motivation related symptoms may affect effort during neuropsychological testing. Performance Validity Tests (PVT's) are therefore essential, but are rarely mentioned in research on cognitive functioning in MDD. We aimed to assess the proportion of MDD patients with demonstrated valid performance and determine cognitive functioning in patients with valid performance. This is the first systematic review on neuropsychological performance validity in MDD. METHODS: Databases PubMed, PsycINFO, Embase, and Cochrane Library were searched for studies reporting on PVT results of adult MDD patients. We meta-analyzed the proportion of MDD patients with PVT scores indicative of valid performance. RESULTS: Seven studies with a total of 409 MDD patients fulfilled inclusion criteria. Six studies reported the exact proportion of patients with PVT scores indicative of valid performance, which ranged from 60 to 100 % with a proportion estimate of 94 %. Four studies reported on cognitive functioning in MDD patients with valid performance. Two out of these studies found memory impairment in a minority of MDD patients and two out of these studies found no cognitive impairment. LIMITATIONS: Small number of studies and small sample sizes. CONCLUSIONS: A surprisingly small number of studies reported on PVT in MDD. About 94 % of MDD patients in studies using PVT's had valid neuropsychological test performance. Concessive information regarding cognitive functioning in MDD patients with valid performance was lacking. Neuropsychological performance validity should be taken into account since this may alter conclusions regarding cognitive functioning.

Effects up to 20-Year Follow-Up of Preventive Cognitive Therapy in Adults Remitted from Recurrent Depression: The DELTA Study.

INTRODUCTION: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression. OBJECTIVE: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient. METHODS: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes. RESULTS: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity. CONCLUSIONS: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years.

Comparison of Postoperative Neurocognitive Function in Older Adult Patients with and without Diabetes Mellitus.

INTRODUCTION: Delayed neurocognitive recovery (DNR; neurocognitive disorder up to 30 days postoperative) and postoperative neurocognitive disorders (POCD; neurocognitive disorder 1-12 months postoperative) occur frequently after surgery, with diabetes mellitus (DM) suggested to contribute to this. This was a single-center prospective cohort study. The main aim of this study was to investigate the role of DM and preoperative hemoglobin A1c (HbA1c) in the development of POCDs after noncardiac surgery. METHODS: Older adult patients ≥65 years of age scheduled for elective surgery were recruited. The Modified Telephone Interview for Cognitive Status questionnaire (TICS-M), a test of global cognitive functioning, was administered to determine cognition. Preoperative, 30-day postoperative, and 6-month postoperative cognition were compared for patients with and without DM. Cognitive decline was subdivided into mild (1 to 2 standard deviations below controls) and major (≥2 standard deviations below controls) DNR or POCD. Preoperative HbA1c levels were correlated with TICS-M scores. RESULTS: We analyzed 102 patients [median (IQR [range]) age 72.0 (5 [68-74])]), who were divided into patients with DM (80 patients [78%]) and patients without DM (22 patients [22%]). Baseline cognitive function was similar for both groups. Repeated measures ANOVA showed that mean DM patient TICS-M scores decreased 30 days postoperative (F(2, 200) = 4.0, p = 0.02), with subsequent recovery 6-month postoperative, compared to stable TICS-M scores in non-DM patients. There were significantly more DM patients with DNR than non-DM patients (n = 11 [50%] vs. n = 14 [17.5%]; p = 0.031). There were no between-group differences in mild or major POCD. Higher preoperative HbA1c levels were significantly correlated with decreased 30-day Δcognition scores (F(1, 54) = 9.4, p = 0.003) with an R2 of 0.149 (ß -0.45, 95% confidence interval: -0.735 to -0.154). CONCLUSIONS: Older adult patients with DM undergoing surgery have an increased risk of DNR compared to older adult non-DM patients, but no increased risk of POCD. In DM patients, higher preoperative HbA1c levels were associated with an increased risk of DNR.

A blended eHealth intervention for insomnia following acquired brain injury: a randomised controlled trial.

The high prevalence and severe consequences of poor sleep following acquired brain injury emphasises the need for an effective treatment. However, treatment studies are scarce. The present study evaluates the efficacy of blended online cognitive behavioural therapy for insomnia (eCBT-I) developed specifically for people with acquired brain injury. In a multicentre prospective, open-label, blinded end-point randomised clinical trial, 52 participants with insomnia and a history of a stroke or traumatic brain injury were randomised to 6 weeks of guided eCBT-I or treatment as usual, with a 6-week follow-up. The primary outcome measure was the change in insomnia severity between baseline and after treatment, measured with the Insomnia Severity Index. Results showed that insomnia severity improved significantly more with eCBT-I than with treatment as usual compared to baseline, both at post-treatment (mean [SEM] 4.0 [1.3] insomnia severity index points stronger decrease, d = 0.96, p < 0.003) and at follow-up (mean [SEM] 3.2 [1.5] insomnia severity index points, d = -0.78, p < 0.03). In conclusion, our randomised clinical trial shows that blended CBT is an effective treatment for insomnia, and feasible for people with acquired brain injury, regardless of cognitive and psychiatric complaints. Online treatment has major advantages in terms of availability and cost and may contribute to the successful implementation of insomnia treatment for people with acquired brain injuries.

Can people with poststroke insomnia benefit from blended cognitive behavioral therapy? A single case experimental design.

PURPOSE: Sleep is essential for our overall health and wellbeing. Unfortunately, stroke often induces insomnia, which has been shown to impede rehabilitation and recovery of function. Cognitive behavioral therapy for insomnia (CBT-I) is the treatment of choice for insomnia in the general population and is efficacious both when delivered face-to-face or online. The primary aim of this study was to evaluate efficacy of blended CBT-I (eCBT-I) in five poststroke participants with insomnia according to DSM-5 criteria. METHODS: A randomized multiple baseline design was used to evaluate improvements in total sleep time, sleep onset latency, sleep efficiency, nocturnal awakenings and sleep quality. The intervention included six weeks of eCBT-I combined with two face-to-face sessions. RESULTS: All participants completed the intervention. One participant stopped using the diary, while the other four completed it fully. All five sleep diary measures improved, significantly so for nocturnal awakenings. Moreover, after completion of the treatment, four out of five participants no longer fulfilled DSM-5 criteria for insomnia disorder. CONCLUSIONS: This is the first study to show that blended CBT-I is potentially effective in participants with post-stroke insomnia. The findings justify extension to a randomized controlled trial.

Augmenting neurocognitive remediation therapy to Preventive Cognitive Therapy for partially remitted depressed patients: protocol of a pragmatic multicentre randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD) affects 163 million people globally every year. Individuals who experience subsyndromal depressive symptoms during remission (ie, partial remission of MDD) are especially at risk for a return to a depressive episode within an average of 4 months. Simultaneously, partial remission of MDD is associated with work and (psycho)social impairment and a lower quality of life. Brief psychological interventions such as preventive cognitive therapy (PCT) can reduce depressive symptoms or relapse for patients in partial remission, although achieving full remission with treatment is still a clinical challenge. Treatment might be more effective if cognitive functioning of patients is targeted as well since cognitive problems are the most persisting symptom in partial remission and predict poor treatment response and worse functioning. Studies show that cognitive functioning of patients with (remitted) MDD can be improved by online neurocognitive remediation therapy (oNCRT). Augmenting oNCRT to PCT might improve treatment effects for these patients by strengthening their cognitive functioning alongside a psychological intervention. METHODS AND ANALYSIS: This study will examine the effectiveness of augmenting oNCRT to PCT in a pragmatic national multicentre superiority randomised controlled trial. We will include 115 adults partially remitted from MDD with subsyndromal depressive symptoms defined as a Hamilton Depression Rating Scale score between 8 and 15. Participants will be randomly allocated to PCT with oNCRT, or PCT only. Primary outcome measure is the effect on depressive symptomatology over 1 year. Secondary outcomes include time to relapse, cognitive functioning, quality of life and healthcare costs. This first dual approach study of augmenting oNCRT to PCT might facilitate full remission in partially remitted individuals as well as prevent relapse over time. ETHICS AND DISSEMINATION: Ethical approval was obtained by Academic Medical Center, Amsterdam. Outcomes will be made publicly available. TRIAL REGISTRATION NUMBER: NL9582.

Level I PD-MCI Using Global Cognitive Tests and the Risk for Parkinson's Disease Dementia.

Background: The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown. Methods: The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD. Results: PD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P = <0.001). The C-statistics for MMSE (0.72) and MoCA (0.70) were lower than those based on neuropsychological tests (Level I = 0.82; Level II = 0.81). Sensitivity, specificity and diagnostic accuracy balance was best in Level II. Conclusion: MMSE and MoCA predict conversion to PDD. However, Level II neuropsychological assessment seems the preferred assessment for PD-MCI.

General Anesthesia vs Local Anesthesia in Microelectrode Recording-Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial.

Importance: It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease. Objective: To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study. Design, Setting, and Participants: This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS. Interventions: Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead. Main Outcomes and Measures: The primary outcome variable was the between-group difference in cognitive, mood, and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson's Disease Rating Scale, the patient assessment of surgical burden and operative time. Results: A total of 110 patients were randomized to awake (local anesthesia; n = 56; mean [SD] age, 60.0 (7.4) years; 40 [71%] male) or to asleep (general anesthesia; n = 54; mean [SD] age, 61.3 [7.9] years; 38 [70%] male) DBS surgery. The 6-month follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood, and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio, 0.7 [95% CI, 0.3-1.7]). There was no difference in improvement in the off-medication Movement Disorders Society Unified Parkinson's Disease Rating Scale Motor Examination scores between groups (awake group: mean [SD], -27.3 [17.5] points; asleep group: mean [SD], -25.3 [14.3] points; mean difference, -2.0 [95% CI, -8.1 to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery. Conclusions and Relevance: There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures. Trial Registration: trialregister.nl Identifier: NTR5809.

Parkinson disease-associated cognitive impairment.

Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.