Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

BACKGROUND: Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). OBJECTIVES: The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. METHODS: This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. RESULTS: On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). CONCLUSION: Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Structural neuroimaging changes associated with subjective cognitive decline from a clinical sample.

BACKGROUND: Alzheimer's disease (AD) is characterized by progressive deterioration of cognitive functions. Some individuals with subjective cognitive decline (SCD) are in the early phase of the disease and subsequently progress through the AD continuum. Although neuroimaging biomarkers could be used for the accurate and early diagnosis of preclinical AD, the findings in SCD samples have been heterogeneous. This study established the morphological differences in brain magnetic resonance imaging (MRI) findings between individuals with SCD and those without cognitive impairment based on a clinical sample of patients defined according to SCD-Initiative recommendations. Moreover, we investigated baseline structural changes in the brains of participants who remained stable or progressed to mild cognitive impairment or dementia. METHODS: This study included 309 participants with SCD and 43 healthy controls (HCs) with high-quality brain MRI at baseline. Among the 99 subjects in the SCD group who were followed clinically, 32 progressed (SCDp) and 67 remained stable (SCDnp). A voxel-wise statistical comparison of gray and white matter (WM) volume was performed between the HC and SCD groups and between the HC, SCDp, and SCDnp groups. XTRACT ATLAS was used to define the anatomical location of WM tract damage. Region-of-interest (ROI) analyses were performed to determine brain volumetric differences. White matter lesion (WML) burden was established in each group. RESULTS: Voxel-based morphometry (VBM) analysis revealed that the SCD group exhibited gray matter atrophy in the middle frontal gyri, superior orbital gyri, superior frontal gyri, right rectal gyrus, whole occipital lobule, and both thalami and precunei. Meanwhile, ROI analysis revealed decreased volume in the left rectal gyrus, bilateral medial orbital gyri, middle frontal gyri, superior frontal gyri, calcarine fissure, and left thalamus. The SCDp group exhibited greater hippocampal atrophy (p < 0.001) than the SCDnp and HC groups on ROI analyses. On VBM analysis, however, the SCDp group exhibited increased hippocampal atrophy only when compared to the SCDnp group (p < 0.001). The SCD group demonstrated lower WM volume in the uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and callosum forceps than the HC group. However, no significant differences in WML number (p = 0.345) or volume (p = 0.156) were observed between the SCD and HC groups. CONCLUSIONS: The SCD group showed brain atrophy mainly in the frontal and occipital lobes. However, only the SCDp group demonstrated atrophy in the medial temporal lobe at baseline. Structural damage in the brain regions was anatomically connected, which may contribute to early memory decline.

Clusters of cognitive performance predict long-term cognitive impairment in elderly patients with subjective memory complaints and healthy controls.

INTRODUCTION: Patients with subjective memory complaints (SMC) may include subgroups with different neuropsychological profiles and risks of cognitive impairment. METHODS: Cluster analysis was performed on two datasets (n: 630 and 734) comprising demographic and neuropsychological data from SMC and healthy controls (HC). Survival analyses were conducted on clusters. Bayesian model averaging assessed the predictive utility of clusters and other biomarkers. RESULTS: Two clusters with higher and lower than average cognitive performance were detected in SMC and HC. Assignment to the lower performance cluster increased the risk of cognitive impairment in both datasets (hazard ratios: 1.78 and 2.96; Plog-rank: 0.04 and <0.001) and was associated with lower hippocampal volumes and higher tau/amyloid beta 42 ratios in cerebrospinal fluid. The effect of SMC was small and confounded by mood. DISCUSSION: This study provides evidence of the presence of cognitive clusters that hold biological significance and predictive value for cognitive decline in SMC and HC. HIGHLIGHTS: Patients with subjective memory complaints include two cognitive clusters. Assignment to the lower performance cluster increases risk of cognitive impairment. This cluster shows a pattern of biomarkers consistent with incipient Alzheimer's disease pathology. The same cognitive cluster structure is found in healthy controls. The effect of memory complaints on risk of cognitive decline is small and confounded.

Effects of Cognitive Rehabilitation on Cognition, Apathy, Quality of Life, and Subjective Complaints in the Elderly: A Randomized Controlled Trial.

OBJECTIVE: To determine the efficacy of a new-generation integrative cognitive rehabilitation (CR) program (Rehacop) on cognition, clinical symptoms, quality of life (QoL), and subjective complaints in the elderly. DESIGN: A randomized controlled trial study with a cohort of elderly people over 55 years of age. SETTING: Communities of the Basque Country (Spain). PARTICIPANTS: A total of 124 elderly participants (aged 79.00 ± 8.85 years) were randomized in the Rehacop group (RG) (n = 62) and control group (CG) (n = 62). INTERVENTION: The RG attended 39 CR sessions for 3 months (3 sessions/week, 60-minute/session) with the Rehacop program. The CG performed occupational tasks with the same frequency and duration as the RG. METHODS: Participants underwent a neuropsychological assessment at baseline and post-treatment which included cognitive, clinical, and functional tests. In addition, participants and their formal caregivers completed a subjective complaints questionnaire. The data were analyzed according to the intention to treat analysis and with participants who completed the study. This study was registered at clinicaltrials.gov (NCT03435029). RESULTS: The RG showed significant improvements compared to the CG in neurocognition (ANCOVA timexgroup interaction effect size (ηp2)=0.05, 90% confidence interval (CI) = 0.00-0.12). The RG also reduced apathy (ηp2=0.06, 90% CI = 0.01-0.15) and participants' subjective complaints (ηp2=0.11, 90% CI = 0.03-0.21) and improved QoL (ηp2=0.08, 90% CI = 0.01-0.17). CONCLUSIONS: Participants who attended the intervention improved their cognition, QoL, and reduced apathy and subjective complaints after treatment. These findings provide a new understanding of the benefits of CR in the elderly.

A Neuropsychological Rehabilitation Program for Cognitive Impairment in Psychiatric and Neurological Conditions: A Review That Supports Its Efficacy.

Neuropsychological rehabilitation has been the focus of much scientific research over the past decades due to its efficacy in different pathologies. Advances in the neuropsychology field have led to improvements and changes in neuropsychological interventions, which in turn have given rise to different approaches and rehabilitation programs. REHACOP is an integrative neuropsychological rehabilitation program designed by specialist neuropsychologists. With an integrated bottom-up and top-down approach, REHACOP includes neurocognition, social cognition, and daily living tasks hierarchically organized on an increasing level of difficulty. Task arrangement is addressed to maximize improvements and transfer effects into participant's daily living. To date, REHACOP has been implemented on different clinical samples such as patients with schizophrenia, multiple sclerosis (MS), and Parkinson's disease (PD). This manuscript presents the efficacy data of REHACOP across these three populations and discusses it in the context of the available literature. Overall, the magnitude of improvements obtained by means of REHACOP ranged from medium to high across samples. These changes were not restricted to specific neurocognitive domains since participants attending the REHACOP program also showed changes in social cognition and daily functioning variables by means of both direct and transfer effects. Results regarding REHACOP's efficacy in psychiatric and neurological conditions have contributed to expanding the existing evidence about the use of structured neuropsychological rehabilitation. In addition, the results obtained after its implementation highlighted the need and importance of designing and implementing integrative neuropsychological rehabilitation programs that are focused not only on cognition per se but also on participants' performance in daily living.

The impact of apathy on cognitive performance in the elderly.

OBJECTIVES: To examine the impact of apathy on cognitive performance in the elderly following the conceptual principles proposed by Marin1 and Stuss et al2 and to determine the role of the symptoms of apathy in different cognitive domains. METHODS: Cross-sectional study with a cohort of healthy elderly subjects over 55 years old (n = 140). One hundred forty healthy-elderly subjects (aged 79.24 ± 8.6 years old) were recruited from 12 day centers in Northern Spain. Participants underwent a neuropsychological battery, which evaluated Mini Mental State Examination (MMSE), attention, processing speed, verbal fluency, visual and verbal memory, working memory, and executive functioning. Apathy was assessed by the Lille Apathy Rating Scale (LARS), which is composed of four factors: intellectual curiosity, emotion, action initiation, and self-awareness. Correlation and linear regression analyses were performed. RESULTS: In the correlational analysis, the LARS total score correlated negatively with global cognition, verbal fluency, and visual and verbal memory. The intellectual curiosity factor correlated negatively with all cognitive domains except attention. The emotion factor correlated negatively with visual memory. No correlation was found between the action initiation and self-awareness factors or any of the cognitive variables. Multiple stepwise regression analysis showed that symptoms of apathy explained cognitive performance in attention, processing speed, verbal fluency, visual and verbal memory, working memory, executive functioning, and MMSE. CONCLUSIONS: Apathy was significantly associated with cognitive performance, especially with the intellectual curiosity factor. Our results suggest that specific symptoms of apathy contribute differently to individual cognitive domains.

RNAseq based transcriptomics study of SMCs from carotid atherosclerotic plaque: BMP2 and IDs proteins are crucial regulators of plaque stability.

Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease. Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type. The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation. The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques. Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR. Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype. Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes. On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture. Our results substantiate an important role of SMCs in carotid atheroma plaque disruption.