RESUMO
OBJECTIVES: To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI). METHODS: 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function. RESULTS: At baseline, the MCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction (PD) = 90-99%). The MCI[TBI+] group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%). CONCLUSIONS: Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.
Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Substância Cinzenta , Imageamento por Ressonância Magnética , Humanos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/diagnóstico por imagem , Masculino , Feminino , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/complicações , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Idoso , Pessoa de Meia-Idade , Estudos Longitudinais , Testes Neuropsicológicos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Teorema de BayesRESUMO
Background: Driving is the preferred mode of transportation for adults across the healthy age span. However, motor vehicle crashes are among the leading causes of injury and death, especially for older adults, and under distracted driving conditions. Understanding the neuroanatomical basis of driving may inform interventions that minimize crashes. This exploratory study examined the neuroanatomical correlates of undistracted and distracted simulated straight driving. Methods: One-hundred-and-thirty-eight participants (40.6% female) aged 17-85 years old (mean and SD = 58.1 ± 19.9 years) performed a simulated driving task involving straight driving and turns at intersections in a city environment using a steering wheel and foot pedals. During some straight driving segments, participants responded to auditory questions to simulate distracted driving. Anatomical T1-weighted MRI was used to quantify grey matter volume and cortical thickness for five brain regions: the middle frontal gyrus (MFG), precentral gyrus (PG), superior temporal cortex (STC), posterior parietal cortex (PPC), and cerebellum. Partial correlations controlling for age and sex were used to explore relationships between neuroanatomical measures and straight driving behavior, including speed, acceleration, lane position, heading angle, and time speeding or off-center. Effects of interest were noted at an unadjusted p-value threshold of 0.05. Results: Distracted driving was associated with changes in most measures of straight driving performance. Greater volume and cortical thickness in the PPC and cerebellum were associated with reduced variability in lane position and heading angle during distracted straight driving. Cortical thickness of the MFG, PG, PPC, and STC were associated with speed and acceleration, often in an age-dependent manner. Conclusion: Posterior regions were correlated with lane maintenance whereas anterior and posterior regions were correlated with speed and acceleration, especially during distracted driving. The regions involved and their role in straight driving may change with age, particularly during distracted driving as observed in older adults. Further studies should investigate the relationship between distracted driving and the aging brain to inform driving interventions.
RESUMO
Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition.
Assuntos
Tronco Encefálico , COVID-19 , Fadiga , Imageamento por Ressonância Magnética , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , Masculino , Feminino , Fadiga/diagnóstico por imagem , Fadiga/etiologia , Fadiga/patologia , Pessoa de Meia-Idade , Adulto , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia , Idoso , Putamen/diagnóstico por imagem , Putamen/patologia , SARS-CoV-2RESUMO
OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.
Assuntos
Doença de Alzheimer , Transtornos Cerebrovasculares , Disfunção Cognitiva , Doença de Parkinson , Humanos , Estudos Transversais , Doença de Parkinson/psicologia , Estudos Longitudinais , Disfunção Cognitiva/psicologia , Doença de Alzheimer/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Transtornos Cerebrovasculares/complicações , Testes NeuropsicológicosRESUMO
INTRODUCTION: Traumatic brain injury (TBI) is associated with an accelerated course of dementia, although biological relationships are incompletely understood. METHODS: The study examined 1124 participants, including 343 with Alzheimer disease (AD), 127 with AD with TBI, 266 cognitively normal adults with TBI, and 388 cognitively normal adults without TBI. Cortical thickness was quantified from T1-weighted magnetic resonance imaging data. Multiple linear regression was used to determine the interaction between AD and TBI on cortical thickness. RESULTS: Among those with AD, TBI was associated with an earlier age of AD onset but, counterintuitively, less cortical thinning in frontotemporal regions relative to non-AD controls. DISCUSSION: AD with TBI represents a distinct group from AD, likely with distinct pathologic contributions beyond gray matter loss. This finding has important implications for the diagnosis and treatment of AD in the presence of TBI and indicates that models of AD, aging, and neural loss should account for TBI history.
Assuntos
Doença de Alzheimer , Lesões Encefálicas Traumáticas , Humanos , Doença de Alzheimer/diagnóstico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Envelhecimento/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
INTRODUCTION: Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. METHODS: Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. RESULTS: No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. CONCLUSIONS: These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.
Assuntos
Teste para COVID-19 , COVID-19 , Humanos , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , COVID-19/complicações , Encéfalo/fisiologia , Cefaleia/diagnóstico por imagem , Cefaleia/etiologiaRESUMO
Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.
RESUMO
Cognitive resilience in Alzheimer's disease (AD) can be defined as retention of high cognition despite presence of considerable cerebral AD lesions. We sought to identify factors associated with this phenomenon. Data were obtained from National Alzheimer's Coordinating Centre (NACC) dataset. Subjects with severe AD neuropathology, based on National Institute on Aging-Reagan (NIA-Reagan) criteria, no other primary neuropathology, and a ≤ 2-year interval between last follow-up and death were included. Mini-mental status examination score ≥ 24 was used as a proxy for normal cognition. In total, 654 cases were included; 59 (9%) were cognitively resilient. Multivariable logistic regression model showed that resilient participants were more educated, had a lower body mass index (BMI), were more likely to be lifetime/recent smoker or use an anticoagulant/antiplatelet agent, compared with cognitively impaired subjects. In addition to expected protective factors such as higher education and lower BMI, our results showed that smoking (especially recent smoking) and anticoagulant/antiplatelet consumption are associated with resilience to clinical cognitive expression of severe AD pathology. Pharmacological approaches using this information might be explored for clinical AD amelioration.
RESUMO
BACKGROUND: Suicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt. METHODS: MDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC). RESULTS: In MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength. LIMITATIONS: Resting-state scans provided an indirect assessment of SC and the pain network. CONCLUSIONS: These findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Imageamento por Ressonância Magnética , Canadá , Giro do Cíngulo/diagnóstico por imagem , Dor/diagnóstico por imagemRESUMO
The mechanisms for regulating cerebral blood flow (CBF) are highly sensitive to traumatic brain injury (TBI). The perfusion imaging technique may be used to assess CBF and identify perfusion abnormalities following a TBI. Studies have identified CBF disturbances across the injury severity spectrum and correlations with both acute and long-term indices of clinical outcome. Although not yet widely used in the clinical context, this is an important area of ongoing research.
Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Imagem de Perfusão , Imageamento por Ressonância Magnética , EncéfaloRESUMO
OBJECTIVE: To examine the roles of the default mode network (DMN) and executive control network (ECN) in prolonged recovery after mild traumatic brain injury (mTBI), and relationships with indices of white matter microstructural injury. METHODS: Seventeen mTBI patients with persistent symptoms were imaged an average of 21.5 months post-injury, along with 23 healthy controls. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to evaluate functional connectivity (FC) of the DMN and ECN. Diffusion tensor imaging (DTI) quantified fractional anisotropy, along with mean, axial and radial diffusivity of white matter tracts. RESULTS: Compared to controls, patients with mTBI had increased functional connectivity of the DMN and ECN to brain regions implicated in salience and frontoparietal networks, and increased white matter diffusivity within the cerebrum and brainstem. Among the patients, FC was correlated with better neurocognitive test scores, while diffusivity was correlated with more severe self-reported symptoms. The FC and diffusivity values within abnormal brain regions were not significantly correlated. CONCLUSION: For female mTBI patients with prolonged symptoms, hyper-connectivity may represent a compensatory response that helps to mitigate the effects of mTBI on cognition. These effects are unrelated to indices of microstructural injury, which are correlated with symptom severity, suggesting that rs-fMRI and DTI may capture distinct aspects of pathophysiology.
Assuntos
Concussão Encefálica , Síndrome Pós-Concussão , Humanos , Feminino , Síndrome Pós-Concussão/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Função Executiva , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Neuroimaging studies have demonstrated aberrant structure and function of the "cognitive-affective cerebellum" in major depressive disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression. A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 healthy controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI1 corresponded to default mode network (DMN)/inattentive processing; ROI2 corresponded to attentional networks, including frontoparietal, dorsal attention, and ventral attention; ROI3 corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of the cerebellum. A general linear model was used to perform within-group and between-group comparisons. In comparison to HC, participants with MDD displayed increased RsFc within the cerebello-cerebral DMN (ROI1) and significantly elevated RsFc between the cerebellar ROI1 and bilateral angular gyrus at a voxel threshold (p < 0.001, two-tailed) and at a cluster level (p < 0.05, FDR-corrected). Group differences were non-significant for ROI2 and ROI3. These results contribute to the development of a systems neuroscience approach to the diagnosis and treatment of MDD. Specifically, our findings confirm previously reported associations between MDD, DMN, and cerebellum, and highlight the promising role of these functional and anatomical locations for the development of novel imaging-based biomarkers and targets for neuromodulation therapies. ClinicalTrials.gov TRN: NCT01655706; Date of Registration: August 2nd, 2012.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Imageamento por Ressonância Magnética/métodos , Cerebelo/diagnóstico por imagem , Mapeamento Encefálico , Neuroimagem , Vias Neurais/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
This review covers the latest advances in our understanding of psychosis in the elderly population with respect to diagnosis, epidemiology, and treatment. Major topics of discussion include late life psychiatric disorders such as schizophrenia, schizoaffective disorder, and delusional disorder as well as dementia-related psychosis. Clinical differences between early-onset and late-onset disorders are reviewed in terms of prevalence, symptomatology, and approach to treatment. Newly revised research and clinical criteria for dementia-related psychosis are referenced. The evidence base for emerging therapies including citalopram and pimavanserin in relation to conventional therapies such as atypical antipsychotics are discussed..
Assuntos
Antipsicóticos , Demência , Transtornos Psicóticos , Esquizofrenia , Idoso , Humanos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Citalopram/uso terapêutico , Demência/tratamento farmacológicoRESUMO
BACKGROUND: Recent work suggests that APOEÉ4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS). OBJECTIVE: To examine the interaction of sex and APOEÉ4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (nâ=â252) and 2) patients with probable AD (nâ=â7,261). METHODS: Regression models examined the interactive effects of sex and APOEÉ4 on the number of NPS experienced and NPS Severity. APOEÉ3/4 and APOEÉ4/4 were pooled in the at-risk cohort due to the sample size. RESULTS: In the at-risk cohort, there was a significant sex*APOEÉ4 interaction (pâ=â0.007) such that the association of APOEÉ4 with NPS was greater in females than in males (incident rate ratio (IRR)â=â2.0). APOEÉ4/4 females had the most NPS (meanâ=â1.9) and the highest severity scores (meanâ=â3.5) of any subgroup. In the clinical cohort, APOEÉ4/4 females had significantly more NPS (IRRâ=â1.1, pâ=â0.001, meanâ=â3.1) and higher severity scores (bâ=â0.31, pâ=â0.015, meanâ=â3.7) than APOEÉ3/3 females (meanNPSâ=â2.9, meanSeverityâ=â3.3). No association was found in males. CONCLUSION: Our study suggests that sex modifies the association of APOEÉ4 on NPS burden. APOEÉ4/4 females may be particularly susceptible to increased NPS burden among individuals with AD and among individuals at risk for AD. Further investigation into the mechanisms behind these associations are needed.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Transtorno Depressivo Maior , Masculino , Feminino , Humanos , Doença de Alzheimer/diagnóstico , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/complicações , Disfunção Cognitiva/diagnóstico , Testes NeuropsicológicosRESUMO
BACKGROUND: The APOE4 allele is a genetic risk factor for developing late-onset Alzheimer's disease (AD). Previous work by our group revealed that female APOE4 homozygotes with Lewy body (LB) pathology were more likely to experience psychosis compared to female APOE4 non-carriers, whereas in males there was no APOE4 dose-dependent significant effect. The objective of this study was to refine our previous findings by adjusting for covariates and determining the probability of an APOE4 sex-mediated effect on psychosis. METHODS: Neuropathologically confirmed AD patients with LB pathology (n = 491) and without LB pathology (n = 716) were extracted from the National Alzheimer's Coordinating Center (NACC). Patients were classified as psychotic if they scored positively for delusions and/or hallucinations on the Neuropsychiatric Inventory. Analysis consisted of a preliminary unadjusted binary logistic regression and a Generalized Additive binary logistic regression Model (GAM) to predict the relationship between APOE4 status and sex on the presence of psychosis in both cohorts, adjusting for age, education and MMSE. RESULTS: In the cohort with LB pathology, female APOE4 homozygotes were significantly more likely to experience psychosis compared to female APOE4 non-carriers (OR = 4.15, 95%CI [1.21, 14.2], p = 0.023). Female heterozygotes were also more likely to experience psychosis compared to female APOE4 non-carriers, but to a lesser extent (OR = 2.37, 95%CI [1.01, 5.59], p = 0.048). There was no significant difference in males with LB pathology or in any sex in the cohort without LB pathology. CONCLUSIONS: Sex and zygosity influence the effect of APOE4 on psychosis in neuropathologically confirmed AD patients, with the effect being limited to females with LB pathology.
RESUMO
Background: This study examines the relationship between delusional severity in cognitively impaired adults with automatically computed volume and texture biomarkers from the Normal Appearing Brain Matter (NABM) in FLAIR MRI. Methods: Patients with mild cognitive impairment (MCI, n = 24) and Alzheimer's Disease (AD, n = 18) with delusions of varying severities based on Neuropsychiatric Inventory-Questionnaire (NPI-Q) (1mild, 2moderate, 3severe) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed for this task. The NABM region, which is gray matter (GM) and white matter (WM) combined, was automatically segmented in FLAIR MRI volumes with intensity standardization and thresholding. Three imaging biomarkers were computed from this region, including NABM volume and two texture markers called "Integrity" and "Damage". Together, these imaging biomarkers quantify structural changes in brain volume, microstructural integrity and tissue damage. Multivariable regression was used to investigate relationships between imaging biomarkers and delusional severities (1, 2 and 3). Sex, age, education, APOE4 and baseline cerebrospinal fluid (CSF) tau were included as co-variates. Results: Biomarkers were extracted from a total of 42 participants with longitudinal time points representing 164 imaging volumes. Significant associations were found for all three NABM biomarkers between delusion level 3 and level 1. Integrity was also sensitive enough to show differences between delusion level 1 and delusion level 2. A significant specified interaction was noted with severe delusions (level 3) and CSF tau for all imaging biomarkers (p < 0.01). APOE4 homozygotes were also significantly related to the biomarkers. Conclusion: Cognitively impaired older adults with more severe delusions have greater global brain disease burden in the WM and GM combined (NABM) as measured using FLAIR MRI. Relative to patients with mild delusions, tissue degeneration in the NABM was more pronounced in subjects with higher delusional symptoms, with a significant association with CSF tau. Future studies are required to establish potential tau-associated mechanisms of increased delusional severity.
RESUMO
BACKGROUND: The temporal relationship between sleep, Alzheimer's disease (AD), and cognitive impairment remains to be further elucidated. OBJECTIVE: First, we aim to determine whether the Neuropsychiatric Inventory-Questionnaire (NPI-Q) assessed nighttime behaviors prior to cognitive decline influence the rate of cognitive deterioration in pathologically confirmed AD, and second, to assess the possible interactions with APOE allele and cerebral amyloid angiopathy (CAA). METHODS: The rate of cognitive decline between cognitively asymptomatic participants from the National Alzheimer Coordinating Center who eventually received a neuropathologic diagnosis of AD with (+NTB) or without (-NTB) nighttime behaviors were compared using independent samples t-test. Participants were stratified by APOE carrier and CAA status. Demographic and patient characteristics were assessed using descriptive statistics, and the independent samples t-test was used for continuous variables and chi-square test for categorical variables. The significance level was set at p≤0.05. RESULTS: The rate of cognitive decline was greater in +NTB (nâ=â74; 3.30 points/year) than -NTB (nâ=â330; 2.45 points/year) (pâ=â0.016), even if there was no difference in cognitive status at onset. This difference was restricted to APOE É4 carriers (pâ=â0.049) and positive CAA participants (pâ=â0.020). Significance was not reached in non-carriers (pâ=â0.186) and negative CAA (pâ=â0.364). APOE and CAA were not differentially distributed between the NTB groups. CONCLUSION: NPI-Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly deteriorating cognition in patients with AD neuropathology who are also carriers of APOE É4 or show CAA.
Assuntos
Doença de Alzheimer , Angiopatia Amiloide Cerebral , Disfunção Cognitiva , Doença de Alzheimer/patologia , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Angiopatia Amiloide Cerebral/patologia , Cognição , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study. DESIGN: Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed. SETTING: Community-based multi-centered study based in Toronto across 5 academic sites. PARTICIPANTS: Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls. MEASUREMENTS: We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores. RESULTS: A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD. CONCLUSIONS: This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.
Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Transtorno Depressivo Maior , Hipertensão , Estimulação Transcraniana por Corrente Contínua , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Disfunção Cognitiva/psicologia , Estudos de Coortes , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Testes Neuropsicológicos , Fatores de RiscoRESUMO
In the original publication [...].