IMPORTANCE: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. OBJECTIVE: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. MAIN OUTCOMES AND MEASURES: Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. RESULTS: In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. CONCLUSIONS AND RELEVANCE: Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.
- MeSH
- amyloidní beta-protein * mozkomíšní mok metabolismus MeSH
- apolipoprotein E4 genetika MeSH
- biologické markery mozkomíšní mok MeSH
- deprese * MeSH
- dospělí MeSH
- kognitivní dysfunkce * MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty mozkomíšní mok MeSH
- pozitronová emisní tomografie * MeSH
- průřezové studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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.
- MeSH
- Alzheimerova nemoc * krev patologie mozkomíšní mok MeSH
- autofagie * fyziologie MeSH
- biologické markery * mozkomíšní mok krev MeSH
- frontotemporální lobární degenerace * patologie mozkomíšní mok krev MeSH
- homolog Atg1 metabolismus MeSH
- intracelulární signální peptidy a proteiny MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitofagie * MeSH
- proteinkinasy metabolismus krev 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
DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment. DDC levels increased over time in PD, being significantly associated to higher dosages of dopaminergic treatment. This emphasizes the need to consider treatment effect when analyzing plasma DDC, and suggests that plasma DDC, in contrast to CSF DDC, is of limited use as a diagnostic biomarker for LBD, but could be valuable for treatment monitoring.
- MeSH
- biologické markery * krev mozkomíšní mok MeSH
- demence s Lewyho tělísky * farmakoterapie krev mozkomíšní mok MeSH
- DOPA-dekarboxylasa * metabolismus MeSH
- dopaminové látky terapeutické užití MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- Parkinsonova nemoc * farmakoterapie krev 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
- multicentrická studie MeSH
IMPORTANCE: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels. OBJECTIVE: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]). Data from 15 research and memory clinic studies were pooled and harmonized. Participants included individuals for whom data on age, cognitive status, amyloid status, and presence of CMBs were available. Data were analyzed from October 22, 2023, to April 26, 2024. MAIN OUTCOMES AND MEASURES: The main outcomes were age, cognitive status, amyloid status and presence, location, and number of CMBs. Presence of amyloid pathology was determined based on 42 amino acid-long form of amyloid-β peptide (Aβ42) levels in cerebrospinal fluid or on amyloid-positron emission tomography. Presence and, in a subset, location (lobar vs deep) and number of CMBs were determined on magnetic resonance imaging (locally with visual rating). RESULTS: Among 4080 participants included in the analysis, the mean (SD) age was 66.5 (8.9) years, and 2241 (54.9%) were female. A total of 2973 participants had no cognitive impairment (cognitive unimpairment [CU]), and 1107 had mild cognitive impairment (MCI) or AD dementia (ADD). One thousand five hundred and thirteen participants (37.1%) had amyloid pathology, 1368 of 3599 (38.0%) with data available were APOE ε4 carriers, and 648 (15.9%) had CMBs. In the CU group, amyloid pathology and APOE ε4 copy number were not associated with presence of any, no more than 4, or fewer than 2 CMBs but were associated with increased odds of lobar CMBs (odds ratio [OR] for amyloid, 1.42 [95% CI, 1.20-1.69], P < .001; OR for 2 vs 0 alleles, 1.81 [95% CI, 1.19-2.74], P = .006; OR for 1 vs 0 alleles, 1.10 [95% CI, 0.83-1.46], P = .49; and OR for 2 vs 1 allele, 1.64 [95% CI, 0.90-2.97], P = .11; overall P = .02). In the MCI-ADD group, amyloid pathology was associated with presence of any CMBs (OR, 1.51 [95% CI, 1.17-1.96], P = .002), no more than 4 CMBs (OR, 1.44 [95% CI, 1.18-1.82], P = .002), and fewer than 2 CMBs (OR 1.34 [95% CI, 1.03-1.74], P = .03) but not lobar CMBs. APOE ε4 copy number was associated with presence of any (OR for 2 vs 0 alleles, 1.72 [95% CI, 0.88-3.35], P = .11; OR for 1 vs 0 alleles, 0.78 [95% CI, 0.59-1.04], P = .09; and OR for 2 vs 1 allele, 2.20 [95% CI, 1.32-3.67], P = .002; overall P < .001) and no more than 4 CMBs (OR for 2 vs 0 alleles, 1.31 [95% CI, 0.64-2.68], P = .45; OR for 1 vs 0 alleles, 0.75 [95% CI, 0.54-1.04], P = .08; and OR for 2 vs 1 allele, 1.76 [95% CI, 0.97-3.19], P = .06; overall P = .03) but not with fewer than 2 or lobar CMBs. Prevalence estimates of CMBs ranged from 6% at 50 years of age in a non-APOE ε4 allele carrier with no amyloid pathology and no cognitive impairment to 52% at 90 years of age in an APOE ε4 homozygote carrier with amyloid pathology and cognitive impairment. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 4080 participants, prevalence estimates of CMBs were associated with amyloid status, APOE ε4 copy number, and age. CMB prevalence estimates may help inform safety evaluations for antiamyloid clinical trials.
- MeSH
- Alzheimerova nemoc * epidemiologie genetika MeSH
- amyloidní beta-protein * metabolismus mozkomíšní mok MeSH
- amyloidní plaky patologie MeSH
- apolipoprotein E4 genetika MeSH
- biologické markery * mozkomíšní mok MeSH
- cerebrální krvácení * epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- pozitronová emisní tomografie MeSH
- průřezové studie 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
INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.
- MeSH
- Alzheimerova nemoc * patologie MeSH
- atrofie patologie MeSH
- demence s Lewyho tělísky * diagnostické zobrazování patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozková kůra patologie MeSH
- pohlavní dimorfismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This study aims to evaluate the efficacy of the Uniform Data Set (UDS) 2 battery in distinguishing between individuals with mild cognitive impairment (MCI) attributable to Alzheimer's disease (MCI-AD) and those with MCI due to other causes (MCI-nonAD), based on contemporary AT(N) biomarker criteria. Despite the implementation of the novel UDS 3 battery, the UDS 2 battery is still used in several non-English-speaking countries. METHODS: We employed a cross-sectional design. A total of 113 Czech participants with MCI underwent a comprehensive diagnostic assessment, including cerebrospinal fluid biomarker evaluation, resulting in two groups: 45 individuals with prodromal AD (A+T+) and 68 participants with non-Alzheimer's pathological changes or normal AD biomarkers (A-). Multivariable logistic regression analyses were employed with neuropsychological test scores and demographic variables as predictors and AD status as an outcome. Model 1 included UDS 2 scores that differed between AD and non-AD groups (Logical Memory delayed recall), Model 2 employed also Letter Fluency and Rey's Auditory Verbal Learning Test (RAVLT). The two models were compared using area under the receiver operating characteristic curves. We also created separate logistic regression models for each of the UDS 2 scores. RESULTS: Worse performance in delayed recall of Logical Memory significantly predicted the presence of positive AD biomarkers. In addition, the inclusion of Letter Fluency RAVLT into the model significantly enhanced its discriminative capacity. CONCLUSION: Our findings demonstrate that using Letter Fluency and RAVLT alongside the UDS 2 battery can enhance its potential for differential diagnostics.
- MeSH
- Alzheimerova nemoc * diagnóza mozkomíšní mok MeSH
- amyloidní beta-protein mozkomíšní mok MeSH
- biologické markery * mozkomíšní mok MeSH
- diferenciální diagnóza MeSH
- kognitivní dysfunkce * diagnóza etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy * normy statistika a číselné údaje MeSH
- proteiny tau mozkomíšní mok MeSH
- průřezové studie 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
BACKGROUND: Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). OBJECTIVE: We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. METHODS: Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. RESULTS: KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). CONCLUSIONS: Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.
- MeSH
- alely MeSH
- Alzheimerova nemoc * genetika MeSH
- apolipoprotein E4 genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- jednonukleotidový polymorfismus * genetika MeSH
- kognitivní dysfunkce * genetika MeSH
- lidé MeSH
- mozkový neurotrofický faktor genetika MeSH
- neuropsychologické testy MeSH
- paměť fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
There is growing interest in virtual reality (VR) training among competitive athletes and casual sports players alike as a tool to supplement real-life play within a highly controlled, intellectually stimulating environment. We examined data from a commercially available, recently released VR software for tennis for changes in and correlates of performance. Two most frequently used tasks were evaluated-Baseline Center and Quick Volley, which include Efficiency (both), Concentration (both), and Reaction Time (Quick Volley only) subtasks. In all, 1,124 (Baseline Center) and 745 (Quick Volley) users met inclusion criteria (completed more than four trials; active sometime between November 2022 and July 2023). We found that most users were male adults and were about evenly split between advanced/pro users and intermediate/beginner users. Two or three trajectories emerged across the subtasks. Performance gains were most pronounced on movement efficiency, especially early on. Adult users generally exhibited more improvement than junior users. Additionally, women and right-handed users improved more on Baseline Center subtasks, and advanced/pro users did better than intermediate/beginner users on Quick Volley subtasks. We discuss that, despite strong performance gains within VR environment, VR training may still reflect in better real-world performance, may increase confidence and accuracy of relevant movement, lower risk of injury, and present a welcome diversion from a potential monotony of performing sport-related tasks in purely real-world settings. Future research should explore the extent to which VR training transfers to real-world performance.
- MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- psychomotorický výkon fyziologie MeSH
- sportovní výkon * fyziologie MeSH
- tenis * MeSH
- virtuální realita * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
