Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson\u27s Disease

Cognitive and behavioural disturbances in patients with Parkinson’s disease seem to be relatively more frequent after deep brain stimulation of the subthalamic nucleus, as compared with deep brain stimulation of the internal globus pallidus. This finding might be at least partially due to the fact that the subthalamic nucleus is a smaller target, with different neural circuits (motor, associative, and limbic circuits) in close proximity to each other. Thus, electrode misplacements or current spreading to non-motor circuits involving the subthalamic nucleus may give rise to cognitive and behavioural disturbances after subthalamic implants.On the whole, nonetheless, most studies agree about the view that the cognitive and behavioural morbidity of deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease can be considered relatively low, even in the long term, provided that appropriate criteria are used to select candidates for neurosurgery. Further studies are certainly needed to elucidate the pathophysiological mechanisms underlying the postoperative cognitive and behavioural changes which may be observed in Parkinsonian patients treated by deep brain stimulation of the subthalamic nucleu

Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries

Importance Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.Objective To assess the incidence of FTLD across Europe.Design, Setting, and Participants The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and Measures Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.Results Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and Relevance The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.Peer reviewe

Cognitive and behavioural changes after deep brain stimulation of the subthalamic nucleus in Parkinson’s disease

Cognitive and behavioural disturbances in patients with Parkinson’s disease seem to be relatively more frequent after deep brain stimulation of the subthalamic nucleus, as compared with deep brain stimulation of the internal globus pallidus. This finding might be at least partially due to the fact that the subthalamic nucleus is a smaller target, with different neural circuits (motor, associative, and limbic circuits) in close proximity to each other. Thus, electrode misplacements or current spreading to non-motor circuits involving the subthalamic nucleus may give rise to cognitive and behavioural disturbances after subthalamic implants.On the whole, nonetheless, most studies agree about the view that the cognitive and behavioural morbidity of deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease can be considered relatively low, even in the long term, provided that appropriate criteria are used to select candidates for neurosurgery. Further studies are certainly needed to elucidate the pathophysiological mechanisms underlying the postoperative cognitive and behavioural changes which may be observed in Parkinsonian patients treated by deep brain stimulation of the subthalamic nucleu

Which components of famous people recognition are lateralized? A study of face, voice and name recognition disorders in patients with neoplastic or degenerative damage of the right or left anterior temporal lobes

: We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At the familiarity level, we found, as expected, a dissociation between a greater impairment of patients with right ATL lesions on the non-verbal (face and voice) recognition modalities and of those with left ATL lesions on name familiarity. Equally expected were results obtained at the naming level, because the worse naming scores for faces and voices were observed in left-sided patients. Less foregone were, for two reasons, results obtained at the semantic level. First, no difference was found between the two hemispheric groups when scores obtained on the verbal (name) and non-verbal (face and voice) recognition modalities were account for. Second, the face and voice recognition modalities showed a different degree of right lateralization. All group of patients showed, indeed, both at the familiarity and at the semantic level, a greater difficulty in the recognition of voices regarding faces, but this difference reached significance only in patients with right ATL lesions, suggesting a greater right lateralization of the more complex task of voice recognition. A model aiming to explain the greater right lateralization of the more perceptually demanding voice modality of person recognition is proposed

Semantic Relations in a Categorical Verbal Fluency Test: An Exploratory Investigation in Mild Cognitive Impairment

Categorical verbal fluency tests (CFT) are commonly used to assess the integrity of semantic memory in individuals with brain damage. Persons with Dementia of the Alzheimer's Type display a reduced output on CFT, and a similar pattern has been reported in persons with amnesic Mild Cognitive Impairment (aMCI). The aims of the present study were to assess whether the semantic relations between lexical entries produced on a categorical fluency test were different between healthy persons and those with aMCI, and whether this difference was more pronounced in individuals who converted to dementia during a 3-year follow-up period. Methods: We recruited 34 individuals with aMCI and 29 matched healthy persons. During the follow-up period, 10 individuals converted to Dementia (aMCI-conv). Two measures assessing semantic relations between consecutively produced word pairs (Path length and Extended Gloss Overlap) were obtained from the Wordnet database. Results: The number of word pairs analyzed among the healthy participants (HP) and persons with aMCI were 498 (birds: 262; pieces of furniture: 236) and 395 (birds: 174; pieces of furniture: 221), respectively. Path length was lower in aMCI-conv than in HP (p = 0.035), but no differences were found between stable aMCI and HP, and between aMCI-stable and aMCI-conv. The ANOVA for lexical entries belonging to the "birds" category showed a significant effect of group (F = 5.630; p = 0.004); the post hoc analysis showed a significant difference between HP and aMCI-conv (p = 0.003). The "pieces of furniture" category was significantly affected by group (F = 4.107; p = 0.017); the post hoc test showed significant differences between aMCI-conv and healthy individuals (p = 0.049), and between aMCI-conv and stable aMCI (p = 0.001). Discussion: Individuals with aMCI who convert to dementia show a deterioration in the semantic relations between lexical entries, produced on a CFT. This phenomenon may be interpreted as a marker of a very early disruption of semantic memor

Item consistency in retrieving person-specific semantic information from faces and voices: An exploratory study in healthy subjects

Controversies exist over the format of person-specific semantic representations in healthy subjects and the loss of part of these representations in conditions of brain pathology. Some authors have suggested that in brain-damaged patients item-specific consistency of errors through different recognition modalities might indicate a loss of person-specific information. This view is hindered by the fact that item consistency might also be variable in healthy subjects, because names, faces and voices have different degrees of effectiveness in the recognition of familiar people. The aim of the present research was to try to clarify this issue by assessing the value of consistency of semantic retrieval in a large sample of Italian healthy subjects who had judged as familiar the faces and voices of 40 Italian celebrities. The effect of fame level on item consistency was also evaluated. Results showed that the degree of item consistency between faces and voices was rather variable, for example it was influenced by fame level when the latter was based on an integrated (non-verbal) face/voice familiarity score, but not when it was based on the celebritiesâ\u80\u99 names in a (verbal) questionnaire. The consistency between non-verbal assessment of fame and item consistency in retrieving information from faces and voices suggests a different specialization of the left anterior temporal lobe (ATL) for the verbally coded aspects of personal semantics and of the right ATL for the visual (face) and auditory (voice) aspects of person representation

Standardization, Clinical Validation, and Typicality Norms of a New Test Assessing Semantic Verbal Fluency

Objective: Semantic verbal fluency (SVF) tests are widely used in clinical neuropsychology. We propose the standardization and clinical validation of a new SVF test based on the production of names of birds and articles of furniture (Birds and Articles of Furniture test-BAF). Methods: A sample of 268 subjects aged 40 years or more underwent the test. The clinical validation was conducted on subjects affected by amnesic Mild Cognitive Impairment (aMCI; N = 106), mild (N = 178), and moderate (N = 114) Alzheimer's disease (AD). Results: The BAF total score was influenced by both age and education, whereas the single scores obtained on BAF were also influenced by gender. The percentage of subjects with pathological score on BAF increased from aMCI (19%) to mild (45.5%) and moderate (71.1%) AD, and receiver operating characteristic curves analysis showed that the BAF may be highly reliable in distinguishing aMCI and AD patients from healthy subjects. We also provide typicality norms for birds and articles of furniture that could be useful in the assessment of qualitative features of words produced in semantic fluency tests. Conclusions: The BAF test could be a valid and reliable tool in both clinical practice and research on subjects affected by cognitive impairment

The Destiny of Multiple Domain Amnesic Mild Cognitive Impairment: Effect of Alternative Neuropsychological Definitions and Their Adjunctive Role in Respect of Memory Impairment

OBJECTIVE: Mild cognitive impairment is the main risk factor of dementia. Previous evidence has claimed that subjects with memory disturbances associated with impairment of other cognitive domains (multiple domain amnesic MCI) are at the highest risk of developing dementia. To date, a shared definition of amnesic MCI multiple domain (aMCI-MD) is still lacking.METHOD: 163 subjects with aMCI were enrolled and followed-up for 2 years. They underwent a baseline comprehensive neuropsychological battery. The cut-off point for each test was set at 1, 1.5, and 2 SD below the mean obtained in normative studies; aMCI-MD was defined as the occurrence of abnormal scores on at least one, two, or three tests not assessing memory. The Episodic Memory Score (EMS), that measures the severity of memory impairment, was determined. Logistic regressionand Cox's proportional hazard risk models were carried out. The adjunctive effect of the definitions of aMCI-MD on the severity of memory impairment was assessed.RESULTS: Fifty-four subjects progressed to dementia. Only restrictive definitions of aMCI-MD (at least three tests below 1.5 SD; at least two tests below 2 SD) predicted conversion to dementia in both logistic regression and survival analysis. None of the conditions showed a significant adjunctive effect on the EMS.CONCLUSIONS: The predictive effect of impairment in tests assessing cognitive domains other than memory depends on its psychometric definition. The use of a restrictive definition would be of some usefulness, but the adjunctive effect of such a definition on an integrated analysis of memory impairment may be questionable

ARE RAW SCORES ON MEMORY TESTS BETTER THAN AGE- AND EDUCATION-ADJUSTED SCORES FOR PREDICTING PROGRESSION FROM AMNESIC MILD COGNITIVE IMPAIRMENT TO AD ?

In this prospective longitudinal study, conducted in a large sample of amnestic MCI patients over a three-year period, we investigated the recently advanced proposal that unadjusted test scores obtained at baseline on long-term memory tests are more reliable than age- and education-corrected scores in predicting progression from aMCI to AD. Our experimental sample consisted of 270 aMCI patients who underwent extensive neurological and neuropsychological examinations both at baseline and at the follow-up, conducted at least 3 years later. At the follow-up 80 patients had converted to overt dementia. The predictive capacity of raw, age-corrected, education-corrected and fully corrected scores on RAVLT immediate and delayed recall was compared by examining the area under the ROC curves (AUCs) of all of these scores to assess which (raw or corrected) scores achieves the better reliability in predicting conversion to dementia. The condition (aMCI stable vs converted) was analyzed to assess the odds ratios resulting from a logistic regression on the corrected and uncorrected scores of RAVLT immediate and delayed recall. Even if both in immediate and in delayed recall the ROCs of 'raw scores' were generally higher than the other ROCs on corrected scores, these differences did not reach the level of statistical significance, failing to support the claim that unadjusted test scores are superior to age- and education-corrected scores in predicting progression from aMCI to AD