125 research outputs found
Risk of Mild Behavioral Impairment: the role of gender and APOE allele carrier status
Background
Gender differences in dementia and dementiaârelated neuropsychiatric symptoms are well described. Similarly, the Apolipoprotein E (APOE) Δ4 allele is a wellâknown predictor of Alzheimerâs disease. However, their impact on the clinical manifestation of Mild Behavioral Impairment (MBI) remains unclear. Using data from the Australian populationâbased PATH Through Life Study we explored the associations between gender and APOE Δ4 carrier status with MBI. We hypothesized that MBI likelihood would be greater in males and Δ4 carriers.
Method
1316 dementiaâfree participants (48% female; aged 72â79) were included. Gender was selfâreported (female/male). Participants were classified as APOE Δ4+ if they carried at least one Δ4 allele (APOE Δ4/Δ4, Δ2/Δ4, Δ3/Δ4). MBI was approximated using a previously published transformation algorithm, which utilizes items from the Neuropsychiatric Inventory assessed at a single study visit. Binomial logistic regression was used to examine the role of gender and APOE Δ4 carrier status, and their interaction, on predicting MBI status, while controlling for selfâreported years of education.
Result
Of the 1316 participants, 339 (25.8%) were APOE Δ4+ and 445 (34%) had MBI symptoms. A higher proportion of APOE Δ4+ carriers (Ï2 (1) = 5.99, p = .014) and men (Ï2 (1) = 4.59, p = .032) were in the MBI group compared to the nonâMBI group. Binomial logistic regression showed APOE Δ4 carrier status (OR = 1.58, 95% CI: 1.063â2.344) and male gender (OR = 1.45, 95% CI: 1.093â1.925) were associated with a greater likelihood of MBI. Male gender was also associated with a 2âfold greater likelihood of having symptoms of the Decreased Motivation (OR = 2.08, 95% CI: 1.13â3.86) and Impulse Dyscontrol (OR = 2.16, 95% CI: 1.54â3.03) domains. No interaction effects were found between gender and APOE Δ4 carrier status for MBI or any of its domains.
Conclusion
The current study found that in dementiaâfree older adults both male gender and APOE Δ4+ status increased the risk of having MBI. However, no cumulative/interaction effect between gender and APOE Δ4 carrier status was found, suggesting that being both male and APOE Δ4+ does not further increase the risk of MBI. These results provide novel and valuable insight into the connection between gender, APOE Δ4 carrier status and MBI
Neurobiology of delusions in Alzheimerâs disease
Alzheimerâs disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or ApoΔ4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities. Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.peer-reviewe
HipermemĂłria, sinestesia, savants: Luria e Borges revisitados
In this paper, we investigated two subjects with superior memory, or hyper memory: Solomon Shereshevsky, who was followed clinically for years by A. R. Luria, and Funes the Memorious, a fictional character created by J. L. Borges. The subjects possessed hyper memory, synaesthesia and symptoms of what we now call autistic spectrum disorder (ASD). We will discuss interactions of these characteristics and their possible role in hyper memory. Our study suggests that the hyper memory in our synaesthetes may have been due to their ASD-savant syndrome characteristics. However, this talent was markedly diminished by their severe deficit in categorization, abstraction and metaphorical functions. As investigated by previous studies, we suggest that there is altered connectivity between the medial temporal lobe and its connections to the prefrontal cingulate and amygdala, either due to lack of specific neurons or to a more general neuronal dysfunction.Neste artigo, investigamos dois sujeitos com memĂłria superior ou hipermemĂłria: Solomon Shereshevsky, que foi seguido clinicamente por anos por A. R. Luria, e Funes o memorioso, um personagem fictĂcio criado por J. L. Borges. Os sujeitos possuem hipermemĂłria, sinestesia e sintomas do que hoje chamamos de transtorno do espectro autista (TEA). Vamos discutir interaçÔes dessas caracterĂsticas e seu possĂvel papel na memĂłria hiper. Nosso estudo sugere que a hipermemĂłria em nossos sujeitos sinestĂ©sicos pode ser devido Ă s suas caracterĂsticas de sĂndrome do DSA-savant. No entanto, esse talento foi acentuadamente diminuĂdo pelo profundo dĂ©ficit de categorização, abstração e funçÔes metafĂłricas. Conforme investigado por estudos anteriores, sugerimos que hĂĄ conectividade alterada entre o lobo temporal medial e suas conexĂ”es com o cingulado e a amĂgdala prĂ©-frontal, devido Ă falta de neurĂŽnios especĂficos ou a uma disfunção neuronal mais geral.Fil: Fornazzari, Luis. University of Toronto; CanadĂĄFil: Leggieri, Melissa. University of Toronto; CanadĂĄFil: Schweizer, Tom A.. University of Toronto; CanadĂĄFil: Arizaga, RaĂșl Luciano. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Allegri, Ricardo Francisco. FundaciĂłn para la Lucha contra las Enfermedades NeurolĂłgicas de la Infancia; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Fischer, Corinne E.. University of Toronto; Canad
Music Intervention Approaches for Alzheimerâs Disease: A Review of the Literature
Music interventions have been widely adopted as a potential non-pharmacological therapy for patients with Alzheimerâs disease (AD) to treat cognitive and/or behavioral symptoms of the disease. In spite of the prevalence of such therapies, evidence for their effectiveness report mixed results in the literature. The purpose of this narrative review is to investigate the effectiveness of various intervention strategies (music therapy vs. music listening techniques) and music type used in the intervention (individualized vs. non-individualized music) on cognitive and behavioral outcomes for persons with AD. Databases were searched for studies using either active music therapy or music listening techniques over the last 10 years. These studies were in English, included persons with AD dementia, and whose protocol gathered pre- and post-intervention outcome measures. We initially identified 206 papers which were then reduced to 167 after removing duplicates. Further review yielded 13 papers which were extensively reviewed, resulting in a final sample of six papers. Our analysis of these papers suggested that, regardless of the music intervention approach, individualized music regimens provided the best outcomes for the patient. Furthermore, music listening may act as a relaxation technique and therefore provide a long-term impact for the patient, while active music therapy may acts to engage participants through social interaction and provide acute benefits. Our findings suggest that music techniques can be utilized in various ways to improve behavior and cognition
The Neural Correlates of the Clock-Drawing Test in Healthy Aging
Importance: The clock-drawing test (CDT) is an important neurocognitive assessment tool, widely used as a screening test for dementia. Behavioral performance on the test has been studied extensively, but there is scant literature on the underlying neural correlates.Purpose: To administer the CDT naturalistically to a healthy older aging population in an MRI environment, and characterize the brain activity associated with test completion.Main Outcome and Measure: Blood-oxygen-level dependent (BOLD) functional MRI was conducted as participants completed the CDT using novel tablet technology. Brain activity during CDT performance was contrasted to rest periods of visual fixation. Performance on the CDT was evaluated using a standardized scoring system (Rouleau score) and time to test completion. To assess convergent validity, performance during fMRI was compared to performance on a standard paper version of the task, administered in a psychometric testing room.Results: Study findings are reported for 33 cognitively healthy older participants aged 52â85. Activation was observed in the bilateral frontal, occipital and parietal lobes as well as the supplementary motor area and precentral gyri. Increased age was significantly correlated with Rouleau scores on the clock number drawing (R2) component (rho = -0.55, p < 0.001); the clock hand drawing (R3) component (rho = -0.50, p < 0.005); and the total clock (rho = -0.62, p < 0.001). Increased age was also associated with decreased activity in the bilateral parietal and occipital lobes as well as the right temporal lobe and right motor areas.Conclusion and Relevance: This imaging study characterizes the brain activity underlying performance of the CDT in a healthy older aging population using the most naturalistic version of the task to date. The results suggest that the functions of the occipital and parietal lobe are significantly altered by the normal aging process, which may lead to performance decrements
Psychometrics of the patient-reported outcomes measurement information system measures in hemophilia:the applicability of the pediatric item banks
Background: The use of patient-reported outcomes measures (PROMs) is important in hemophilia care, as it facilitates communication between patients and clinicians and promotes patient-centered care. Currently, a variety of PROMs with insufficient psychometric properties are used. Patient-reported outcomes measurement information system (PROMIS) measures, including Computer Adaptive Tests, were designed to measure generically and more efficiently and, therefore, are an alternative for the existing PROMs. Objectives: To assess the feasibility, measurement properties, and outcomes of 8 PROMIS pediatric measures for boys with hemophilia. Methods: In this multicenter study, boys with hemophilia completed 8 PROMIS measures and 2 legacy instruments. Feasibility was determined by the number of completed items and floor or ceiling effects (percentage of participants that achieved the lowest or highest possible score). Reliability was assessed as the percentage of scores with a SE †4.5. Construct validity was evaluated by comparing the PROMIS measures with the legacy instruments. Mean PROMIS T-scores were calculated and compared with the Dutch general population. Results: In total, 77 boys with hemophilia participated. Reliability was good for almost all PROMIS measures and legacy instruments. The total number of completed items varied from 49 to 90 for the PROMIS pediatric measures, while the legacy instruments contained 117 to 130 items. Floor and ceiling effects were observed in both the PROMIS measures (0-39.5%) and legacy instruments (0-66.7%), but were higher for the legacy instruments. Conclusions: The PROMIS pediatric measures are feasible to use for boys with hemophilia. With the use of the PROMIS measures in clinical care and research, a step toward worldwide standardization of PROM administration can be taken.</p
Determining the association of medical co-morbidity with subjective and objective cognitive performance in an inner city memory disorders clinic: a retrospective chart review
<p>Abstract</p> <p>Background</p> <p>Medical co-morbidity may be associated with impaired cognitive function based on prior studies. However, no studies to date have determined to what extent this association is linked to medical illness or other factors that may be linked to medical illness (such as education, income levels, depression or subjective memory loss). The present study examined how medical co-morbidity, socioeconomic status (defined as residential SES), education and depression are associated with subjective and objective memory function in a sample of patients recruited from a university affiliated Memory Disorders Clinic located in a large Canadian inner city teaching hospital.</p> <p>Methods</p> <p>Data was collected from 85 consecutive referrals to an Inner City Memory Disorders Clinic including socio-demographic characteristics, cognitive status and medical co-morbidity. Descriptive and correlational analyses were conducted.</p> <p>Results</p> <p>Impaired objective cognitive function correlated significantly with increased medical co-morbidity and partially with education but not with residential SES or depression. Elevated memory complaints correlated significantly with depression, inversely with residential SES and not at all with medical co-morbidity or education.</p> <p>Conclusions</p> <p>Increased medical co-morbidity is significantly associated with impaired cognitive performance but not with subjective memory complaints in an Inner City Memory Clinic sample.</p
Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases
Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimerâs disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinsonâs disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases
Exploratory Assessment of K-means Clustering to Classify 18F-Flutemetamol Brain PET as Positive or Negative
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.Rationale: We evaluated K-means clustering to classify amyloid brain PETs as positive or negative.
Patients and Methods: Sixty-six participants (31 men, 35 women; age range, 52â81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 demen- tia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 ParkinsonâLewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID soft- ware (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/ nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpreta- tion based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data.
Results: Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal partici- pants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with ParkinsonâLewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%.
Conclusions: K-means clustering may be a powerful algorithm for classifying amyloid brain PET.This is a multisite project of the Toronto Dementia Research Alli- ance (www.tdra.utoronto.ca) partly funded by Brain Canada, The Edward Foundation, the Canadian Institutes of Health Research (FDN 159910), the LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, and the Dr Sandra Black Cen- tre for Brain Resilience and Recovery. M.F. received support from the Saul A. Silverman Family Foundation as a Canada Interna- tional Scientific Exchange Program and the Morris Kerzner Memo- rial Fund. We gratefully acknowledge GE Healthcare and the CAMH Brain Health Imaging Centre for manufacturing and sup- plying the ligand. We are also grateful to GE Healthcare for provid- ing the software to calculate the brain region of interest SUV ratios. The study protocol, Brain Eye Amyloid Memory study (BEAM), is registered at https://clinicaltrials.gov/ct2/show/NCT02524405? term=beam+sandra+black&rank=1
Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative
Objectives: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit\u27s Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders?. Methods/Design: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer\u27s disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson\u27s disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. Results: We found three components in the ZBI. The first was âoverall burdenâ and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = â0.566, basic ADLs r = â0.43), (2) moderately related to cognition (MoCA r = â0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. Conclusions: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions
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