Nejvíce citovaný článek - PubMed ID 3204199
BACKGROUND: It is challenging for bipolar disorder (BD) studies to capture multiple mood states within a participant at in-person visits. Mood tracking could aid scheduling, but evaluation is usually done using clinical assessments inconvenient for participants to undergo often. However, frequent assessments are necessary to capture dynamic mood changes typical of BD. The Aktibipo Self-Rating Questionnaire (ASERT) is a simple, self-report mood survey. We examined the utility of collecting the ASERT weekly to assess mood changes and schedule follow-up visits. METHODS: Sixty-one participants with BD completed the ASERT and were administered the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) during a baseline visit. Participants were then sent weekly text messages with an ASERT survey link. If participants exhibited at least a 5-point (later 8-point) change from baseline on either the mania or depression subscale, they were called and administered the MADRS or YMRS. A 10-point change on either phone-delivered clinical scale prompted a follow-up visit. Associations between ASERT subscales and clinical scales were evaluated using Spearman's correlation and robust regression. RESULTS: Mean completion rate was 94.8 % and median completion time was 67 s. The ASERT depression and mania subscales correlated with the MADRS and YMRS at baseline and all follow-up time points. Our screening method aided scheduling, with 15 of 19 participants exhibiting a 10-point change or greater on the MADRS and/or YMRS at Visit 2. CONCLUSIONS: The ASERT can be feasibly deployed to track mood and can help schedule follow-up assessments in BD longitudinal studies.
- Klíčová slova
- Bipolar disorder, Depression, Longitudinal studies, Mania, Mood tracking,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.
- Klíčová slova
- Allocentric navigation, Amyloid-β, Egocentric navigation, Entorhinal cortex, Hippocampus, Tau protein,
- MeSH
- Alzheimerova nemoc * genetika mozkomíšní mok diagnostické zobrazování komplikace patofyziologie patologie MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- apolipoprotein E4 * genetika MeSH
- apolipoproteiny E * genetika MeSH
- atrofie MeSH
- biologické markery mozkomíšní mok MeSH
- genotyp MeSH
- kognitivní dysfunkce * genetika mozkomíšní mok diagnostické zobrazování patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek patologie diagnostické zobrazování MeSH
- neuropsychologické testy MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- pozitronová emisní tomografie MeSH
- prostorová navigace * fyziologie MeSH
- proteiny tau mozkomíšní mok MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amyloid beta-protein (1-42) MeSH Prohlížeč
- amyloidní beta-protein MeSH
- apolipoprotein E4 * MeSH
- apolipoproteiny E * MeSH
- biologické markery MeSH
- peptidové fragmenty MeSH
- proteiny tau MeSH
Maintaining cellular homeostasis by removing damaged and senescent mitochondria, a process termed mitophagy, is crucial in preventing Alzheimer's disease (AD) and represents a promising therapeutic target. Our previous research revealed altered mitophagy biomarkers, such as increased CSF and serum PINK1 and serum BNIP3L and decreased serum TFEB levels, indicating impaired autophagy-lysosomal degradation in the AD continuum. However, the role of autophagy/mitophagy in frontotemporal lobar degeneration (FTLD) remains unclear. This study investigated the biomarkers of autophagy/mitophagy and lysosomal biogenesis (PINK1, ULK1, BNIP3L, and TFEB) in biofluids (CSF and serum) from 308 biomarker-defined individuals across the FTLD continuum (FTLD-dementia, n = 29; FTLD-MCI, n = 33) and compared them with those across the AD continuum (MCI-AD, n = 100; AD-dementia, n = 100) and cognitively unimpaired (CU) controls (n = 46) recruited from Czech Brain Aging Study. Additionally, we compared the mitophagy biomarkers across different FTLD clinical subtypes (frontal, semantic and nonfluent variant) with CU, and explored the association between mitophagy biomarkers and clinical phenotypes of FTLD (biomarkers of tau, biomarkers of neurodegeneration, cognition and ATN profile).Our findings indicated a significantly lower CSF PINK1 and ULK1 levels in FTLD compared to AD, with FTLD dementia showing particularly low CSF PINK1 levels compared to AD-dementia. Conversely, CSF ULK1 levels were higher in FTLD-MCI compared to AD-dementia. Serum analyses revealed lower PINK1 and higher TFEB levels in FTLD dementia compared to AD dementia. This study provides compelling evidence of distinct alterations in autophagy/mitophagy biomarkers between FTLD and AD, indicating that these neurodegenerative diseases may affect the cellular waste disposal system through different pathways. This is the first study to explore mitophagy biomarkers in human CSF and serum in FTLD, opening avenues for further research and potential clinical applications.
- Klíčová slova
- Autophagy, Frontotemporal lobar degeneration, MAPT, Neurocognitive impairment, PINK1, TDP-43, TFEB,
- MeSH
- Alzheimerova nemoc * mozkomíšní mok metabolismus patologie krev MeSH
- autofagie * fyziologie MeSH
- biologické markery mozkomíšní mok krev MeSH
- frontotemporální lobární degenerace * mozkomíšní mok metabolismus patologie krev MeSH
- homolog Atg1 mozkomíšní mok MeSH
- intracelulární signální peptidy a proteiny MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitofagie * fyziologie MeSH
- proteinkinasy mozkomíšní mok MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- homolog Atg1 MeSH
- intracelulární signální peptidy a proteiny MeSH
- proteinkinasy MeSH
- PTEN-induced putative kinase MeSH Prohlížeč
- ULK1 protein, human MeSH Prohlížeč
PURPOSE: Child abuse and trauma are significant risk factors in the etiology of borderline personality disorder (BPD). Apart from affecting the risk of developing BPD, adverse childhood experiences seem to increase its symptoms and related disability. Self-stigma presents another common issue with equally prominent consequences for mental health. Despite being theoretically linked, the connections among childhood trauma, self-stigma, and mental health have not been explored in patients with BPD. This study aimed to provide first insights into this understudied topic. PATIENTS AND METHODS: This cross-sectional study included 283 inpatients diagnosed with BPD participating in a residential transdiagnostic psychotherapeutic program. The patients completed several measurements - the Internalized Stigma of Mental Illness Scale, the Childhood Trauma Questionnaire - Short Form, the Clinical Global Impression - Severity, the Beck Depression Inventory-II, the Beck Anxiety Inventory, the Dissociative Experiences Scale, the Sheehan Disability Scale, and a demographic questionnaire. The data was statistically analyzed using IBM SPSS and AMOS 26 programs, and bivariate correlation tests and structural equation modeling explored the hypotheses. RESULTS: Retrospectively reported childhood trauma positively correlated with current self-stigma. Both childhood trauma and self-stigma were also positively related to several indicators of general psychopathology and disability. The significance of these connections was subsequently confirmed by structural equation modeling, where self-stigma acted as a partial mediator of childhood trauma, general psychopathology, and disability. CONCLUSION: Self-stigma significantly mediates the relationship between childhood trauma and selected mental health symptoms among adult patients diagnosed with BPD. Longitudinal studies are necessary to explore the causality of the findings. Therapeutic and societal efforts to tackle childhood trauma or self-stigma might benefit from reflecting its broader psychosocial context.
- Klíčová slova
- anxiety, borderline personality disorder, childhood trauma, depression, disability, self-stigma,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Previous studies have shown that personality traits (i.e., openness to experience, conscientiousness, and agreeableness) relate to prejudicial attitudes. However, one of the aspects of prejudice is social distance; its association with personality traits was overlooked by previous studies. Therefore, this study examines the connection between the Big Five personality traits and social distance toward certain social groups. PARTICIPANTS AND PROCEDURE: Participants from the general population were recruited through leaflets, the institutional webpage, Facebook, and through the project recruitment website and assessed via paper-and-pencil or online form. A total of 214 participants were included (of whom 68.2% were women and the mean age was 32.65, SD = 11.27, range 18-72) who completed the Bogardus Social Distance Scale and the 44-item Big Five Inventory questionnaire. RESULTS: The results showed a relationship between social distance, agreeableness, and openness to experience. Agreeableness seems to lower the social distance toward all studied groups. In comparison, openness to experience seems to lower the social distance towards groups that evoke more polarized attitudes in the majority (e.g., migrants). Furthermore, the influence of demographic characteristics (i.e., age, education level, and gender) is also significant. CONCLUSIONS: This study shows that personality is significantly related to social distancing and expression of prejudicial attitudes. In particular, agreeableness and openness to experience have different effects on social distance and attitudes towards different groups. Further implications are discussed.
- Klíčová slova
- BFI-44, Bogardus Social Distance Scale, personality, social distance,
- Publikační typ
- časopisecké články MeSH
Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology.Abbreviation: Aβ: amyloid beta; AD: Alzheimer disease; AVs: autophagic vacuoles; BNIP3L: BCL2 interacting protein 3 like; CU: cognitively unimpaired; CSF: cerebrospinal fluid; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCI: mild cognitive impairment; NRGN: neurogranin; NEFL: neurofilament light chain; p-MAPT/tau: phosphorylated microtubule associated protein tau; PINK1: PTEN induced kinase 1; t-MAPT/tau: total microtubule associated protein tau; TFEB: transcription factor EB; TMT: Trail Making Test.
- Klíčová slova
- Autophagy, BNIP3L, PINK1, TFEB, mild cognitive impairment, mitophagy,
- MeSH
- Alzheimerova nemoc * mozkomíšní mok krev diagnóza MeSH
- biologické markery * mozkomíšní mok krev metabolismus MeSH
- kognitivní dysfunkce mozkomíšní mok krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny mozkomíšní mok metabolismus krev MeSH
- mitofagie * MeSH
- mozek metabolismus patologie MeSH
- nádorové supresorové proteiny MeSH
- proteinkinasy metabolismus MeSH
- proteiny tau mozkomíšní mok metabolismus MeSH
- protoonkogenní proteiny mozkomíšní mok krev metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktory BHLH-Zip metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery * MeSH
- BNIP3L protein, human MeSH Prohlížeč
- membránové proteiny MeSH
- nádorové supresorové proteiny MeSH
- proteinkinasy MeSH
- proteiny tau MeSH
- protoonkogenní proteiny MeSH
- PTEN-induced putative kinase MeSH Prohlížeč
- TFEB protein, human MeSH Prohlížeč
- transkripční faktory BHLH-Zip MeSH
Impaired spatial navigation is early marker of Alzheimer's disease (AD). We examined ability of self- and informant-reported navigation questionnaires to discriminate between clinically and biomarker-defined participants, and associations of questionnaires with navigation performance, regional brain atrophy, AD biomarkers, and biomarker status. 262 participants (cognitively normal, with subjective cognitive decline, amnestic mild cognitive impairment [aMCI], and mild dementia) and their informants completed three navigation questionnaires. Navigation performance, magnetic resonance imaging volume/thickness of AD-related brain regions, and AD biomarkers were measured. Informant-reported questionnaires distinguished between cognitively normal and impaired participants, and amyloid-β positive and negative aMCI. Lower scores were associated with worse navigation performance, greater atrophy in AD-related brain regions, and amyloid-β status. Self-reported questionnaire scores did not distinguish between the groups and were weakly associated with navigation performance. Other associations were not significant. Informant-reported navigation questionnaires may be a screening tool for early AD reflecting atrophy of AD-related brain regions and AD pathology.
- Klíčová slova
- Clinical neuroscience, Disease, Neuroscience,
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: "SuperAgers" are generally defined as people 80+ years old with episodic memory performance comparable to those 20 years younger. Limited knowledge exists to describe characteristics of SuperAgers, with even less known about Hispanic SuperAgers. METHODS: We examined indicators of cognitive, physical, and psychological resilience in relation to the likelihood of being a SuperAger using data from 2 population-based studies of Hispanic older adults (Puerto Rican Elderly: Health Conditions [PREHCO] Study; Health and Retirement Study [HRS]). SuperAgers were defined as (1) ≥80 years old, (2) recall scores ≥ the median for Hispanic respondents aged 55-64, and (3) no cognitive impairment during the observation period. Overall, 640 PREHCO participants and 180 HRS participants were eligible, of whom 45 (7%) and 31 (17%) met SuperAging criteria. RESULTS: Logistic regressions controlling for age and sex demonstrated that higher education (PREHCO: odds ratio [OR] = 1.20, p < .001; HRS: OR = 1.14, p = .044) and fewer instrumental activities of daily living limitations (PREHCO: OR = 0.79, p = .019; HRS: OR = 0.58, p = .077; cognitive resilience), fewer activities of daily living limitations (PREHCO: OR = 0.72, p = .031; HRS: OR = 0.67, p = .068; physical resilience), and fewer depressive symptoms (PREHCO: OR = 0.84, p = .015; HRS: OR = 0.69, p = .007; psychological resilience) were associated with SuperAging, although not all results reached threshold for statistical significance, presumably due to low statistical power. Additionally, known indicators of physical health (e.g., chronic conditions and self-rated health) did not relate to SuperAging. DISCUSSION: Increasing access to education and recognizing/treating depressive symptoms represent potential pathways to preserve episodic memory among older Hispanic adults.
- Klíčová slova
- Cognitive reserve, Minority aging, Puerto Rico, SuperAgers, Superior memory,
- MeSH
- činnosti denního života psychologie MeSH
- epizodická paměť MeSH
- Hispánci a Latinoameričané * statistika a číselné údaje psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- psychická odolnost * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stárnutí psychologie etnologie MeSH
- stupeň vzdělání MeSH
- zdravotní stav MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Spojené státy americké epidemiologie MeSH
BACKGROUND: Mild behavioral impairment (MBI) has been commonly reported in early Alzheimer's disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity. METHODS: We included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations. RESULTS: MBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared. CONCLUSIONS: MBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.
- Klíčová slova
- Alzheimer’s disease, Mild behavioral impairment, Mild cognitive impairment, Neuropsychiatric symptoms,
- MeSH
- Alzheimerova nemoc * diagnostické zobrazování epidemiologie genetika MeSH
- apolipoproteiny E genetika MeSH
- genotyp MeSH
- kognitivní dysfunkce * diagnostické zobrazování epidemiologie genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- neuropsychologické testy MeSH
- polymorfismus genetický genetika MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- apolipoproteiny E MeSH
- mozkový neurotrofický faktor MeSH
BACKGROUND: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. METHODS: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. RESULTS: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. CONCLUSIONS: The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.
- Klíčová slova
- Borderline personality disorder, Cyberball paradigm, Rejection sensitivity, Social exclusion, Social overinclusion, fMRI,
- Publikační typ
- časopisecké články MeSH