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The present study explores the modifications of cardiovascular autonomic control (CAC) during wake and sleep time and the systemic inflammatory profile associated with exposure to indoor air pollution (IAP) in a cohort of healthy subjects. Twenty healthy volunteers were enrolled. Indoor levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2) and volatile organic compounds (VOCs) were monitored using a portable detector for 7 days. Together, a 7-day monitoring was performed through a wireless patch that continuously recorded electrocardiogram, respiratory activity and actigraphy. Indexes of CAC during wake and sleep time were derived from the biosignals: heart rate and low-frequency to high-frequency ratio (LF/HF) index of sympathovagal balance with higher values corresponding to a predominance of the sympathetic branch. Cyclic variation of heart rate index (CVHRI events/hour) during sleep, a proxy for the evaluation of sleep apnea, was assessed for each night. After the monitoring, blood samples were collected to assess the inflammatory profile. Regression and correlation analysis were performed. A positive association between VOC exposure and the CVHRI (Δ%=+0.2% for 1µg/m3 VOCs, p=0.008) was found. The CVHRI was also positively associated with LF/HF during sleep, thus higher CVHRI values corresponded to a shift of the sympathovagal balance towards a sympathetic predominance (r=0.52; p=0.018). NO2 exposure was positively associated with both the pro-inflammatory biomarker TREM-1 and the anti-inflammatory biomarker IL-10 (Δ%=+1.2% and Δ%=+2.4%, for 1µg/m3 NO2; p=0.005 and p=0.022, respectively). The study highlights a possible causal relationship between IAP exposure and higher risk of sleep apnea events, associated with impaired CAC during sleep, and a pro-inflammatory state counterbalanced by an increased anti-inflammatory response in healthy subjects. This process may be disrupted in vulnerable populations, leading to a harmful chronic pro-inflammatory profile. Thus, IAP may emerge as a critical and often neglected risk factor for the public health that can be addressed through targeted preventive interventions.
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In 2022, stroke emerged as the most significant cerebrovascular disorder globally, causing 6.55 million deaths. Microglia, crucial for CNS preservation, can exacerbate brain damage in ischemic stroke by triggering neuroinflammation. This process is mediated by receptors on microglia, triggering receptors expressed on myeloid cells (TREM-1 and TREM-2), which have contrasting roles in neuroinflammation. In this study, we recruited 38 patients within 4.5 h from the onset of ischemic stroke. The degree of severity was evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) at admission (T0) and after one week of ischemic events (TW) and the Modified Rankin Scale (mRS) at three months. The plasma concentration of TREMs (sTREM) was analyzed by next-generation ELISA at T0 and TW. The sTREM-1 concentrations at T0 were associated with mRS, while the sTREM-2 concentrations at T0 were associated with both the NIHSS at T0 and the mRS. A strong correlation between sTREM-1 and sTREM-2 was observed, suggesting a dependent modulation of the levels. This study provides insights into the potential pathway of TREM-1 and TREM-2 as a future biomarker for stratifying high-risk patients with ischemic stroke.
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Biomarcadores , AVC Isquêmico , Glicoproteínas de Membrana , Receptores Imunológicos , Índice de Gravidade de Doença , Receptor Gatilho 1 Expresso em Células Mieloides , Humanos , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Masculino , Feminino , AVC Isquêmico/metabolismo , AVC Isquêmico/sangue , AVC Isquêmico/patologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/sangue , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/sangue , Idoso , Pessoa de Meia-Idade , Biomarcadores/sangue , Células Mieloides/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/sangue , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: The progressive aging of the population and the increasing complexity of health issues contribute to a growing number of older individuals seeking emergency care. This study aims to assess the state of the art of care provided to older people in the Emergency Departments of Lombardy, the most populous region in Italy, counting over 2 million people aged 65 years and older. METHODS: An online cross-sectional survey was developed and disseminated among emergency medicine physicians and physicians affiliated to the Lombardy section of the Italian Society of Geriatrics and Gerontology (SIGG), during June and July 2023. The questionnaire covered hospital profiles, geriatric consultation practices, risk assessment tools, discharge processes and perspectives on geriatric emergency care. RESULTS: In this mixed method research, 219 structured interviews were collected. The majority of physicians were employed in hospitals, with 54.7% being geriatricians. Critical gaps in older patient's care were identified, including the absence of dedicated care pathways, insufficient awareness of screening tools, and a need for enhanced professional training. CONCLUSIONS: Tailored protocols and geriatric educational programs are crucial for improving the quality of emergency care provided to older individuals. These measures might also help relieve the burden on the Emergency Departments, thereby potentially enhancing overall efficiency and ensuring better outcomes.
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Serviço Hospitalar de Emergência , Humanos , Itália , Estudos Transversais , Idoso , Masculino , Feminino , Inquéritos e Questionários , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , GeriatriaRESUMO
The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247â¯bp and 115â¯bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.
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Biomarcadores , Doenças Cardiovasculares , Ácidos Nucleicos Livres , Humanos , Masculino , Feminino , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Idoso , Ácidos Nucleicos Livres/sangue , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Prognóstico , Fatores de RiscoRESUMO
People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study.
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Envelhecimento , Longevidade , Idoso de 80 Anos ou mais , HumanosRESUMO
Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer's disease (AD). The aim of the present study was to isolate total EVs from plasma and characterize their microRNA (miRNA) contents in AD patients. We isolated total EVs from the plasma of all recruited subjects using ExoQuickULTRA exosome precipitation solution (SBI). Subsequently, circulating total EVs were characterized using Nanosight nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. A panel of 754 miRNAs was determined with RT-qPCR using TaqMan OpenArray technology in a QuantStudio 12K System (Thermo Fisher Scientific). The results demonstrated that plasma EVs showed widespread deregulation of specific miRNAs (miR-106a-5p, miR-16-5p, miR-17-5p, miR-195-5p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-296-5p, miR-30b-5p, miR-532-3p, miR-92a-3p, and miR-451a), some of which were already known to be associated with neurological pathologies. A further validation analysis also confirmed a significant upregulation of miR-16-5p, miR-25-3p, miR-92a-3p, and miR-451a in prodromal AD patients, suggesting these dysregulated miRNAs are involved in the early progression of AD.
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Doença de Alzheimer , Exossomos , Vesículas Extracelulares , MicroRNAs , Humanos , Doença de Alzheimer/genética , MicroRNAs/genética , Biomarcadores , Vesículas Extracelulares/genética , Exossomos/genéticaRESUMO
Inflammaging is a low-grade inflammatory state that can be considered an adaptive process aimed at stimulating appropriate anti-inflammatory response. Frailty is determined by the accumulation of molecular and cellular defects accumulated throughout life; therefore, an appropriate frailty computation could be a valuable tool for measuring biological age. This study aims to analyse the association between inflammatory markers and both chronological age "per se" and frailty. We studied 452 persons aged 43-114 years. A Frailty Index (FI) was computed considering a wide range of age-related signs, symptoms, disabilities, and diseases. Plasma concentrations of inflammatory cytokines and peripheral markers of neuroinflammation were analysed by next-generation ELISA. The mean age of the cohort was 79.7 (from 43 to 114) years and the median FI was 0.19 (from 0.00 to 0.75). The concentrations of most inflammatory markers increased significantly with chronological age, after adjustment for sex and FI. Interferon-γ was significantly affected only by FI, while interleukin (IL)-10 and IL-1ß were associated only with chronological age. In conclusion, we described different associations between inflammatory components and chronological vs. biological age. A better characterization of the molecular signature of aging could help to understand the complexity of this process.
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Fragilidade , Humanos , Idoso , Idoso de 80 Anos ou mais , Fragilidade/diagnóstico , Envelhecimento/fisiologia , Inflamação , CitocinasRESUMO
OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease with health-related quality of life (HRQoL) high impairment. Pain is of paramount importance to be targeted by therapeutical approaches. Our study aim was to perform an add-on device-based non-invasive neuromodulatory treatment through transcutaneous auricular vagal nerve stimulation (tVNS) in patients with SSc, assessing its effects on pain as primary endpoint and on inflammation, cardiovascular autonomic control and HRQoL. METHODS: Thirty-two patients with SSc were enrolled based on reported pain assessed through Numeric Rating Scale (NRS). Twenty-one (90% with limited cutaneous SSc) completed a randomised, cross-over, patient-blind trial, in which interventional and active control were used in random order for 4 weeks, interspersed with 4 weeks washout. NRS, Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) Item4 for pain interference, heart rate variability (HRV), serum cytokines and HRQoL questionnaires (Health Assessment Questionnaire, Patient Health Questionnaire-9, University of California, Los Angeles Gastrointestinal Tract, Pittsburgh Sleep Quality Index) were assessed at baseline, at T1 (after 1 month of tVNS or active control), at T2 (after washout) and at T3 (after 1 month of active control or tVNS). T-test for paired data and Wilcoxon signed-rank test for non-normally distributed parameters were performed to compare the effect of tVNS and active control. RESULTS: NRS pain was significantly reduced by tVNS and not by active control (Mean±SD: -27.7%±21.3% vs -7.7%±26.3%, p=0.002). Interleukin-6 was downregulated in tVNS versus active control (p=0.029). No significant differences were observed in tVNS versus active control for PROMIS-29 Item4, QoL scales and HRV with both spectral and symbolic analyses. CONCLUSION: tVNS demonstrated to be a safe and non-invasive add-on tool to reduce pain in SSc.
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Escleroderma Sistêmico , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Manejo da Dor , Qualidade de Vida , Dor/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapiaRESUMO
Frailty is a geriatric syndrome that results from multisystem impairment caused by age-associated accumulation of deficits. The frailty index is used to define the level of frailty. Several studies have searched for molecular biomarkers associated with frailty, to meet the needs for personalized care. Cyclase-associated protein 2 (CAP2) is a multifunctional actin-binding protein involved in various physiological and pathological processes, that might reflect frailty's intrinsic complexity. This study aimed to investigate the association between frailty index and circulating CAP2 concentration in 467 community-dwelling older adults (median age: 79; range: 65-92 years) from Milan, Italy. The selected robust regression model showed that circulating CAP2 concentration was not associated with chronological age, as well as sex and education. However, circulating CAP2 concentration was significantly and inversely associated with the frailty index: a 0.1-unit increase in frailty index leads to ~0.5-point mean decrease in CAP2 concentration. Furthermore, mean CAP2 concentration was significantly lower in frail participants (i.e., frailty index ≥0.25) than in non-frail participants. This study shows the association between serum CAP2 concentration and frailty status for the first time, highlighting the potential of CAP2 as a biomarker for age-associated accumulation of deficits.
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Proteínas Adaptadoras de Transdução de Sinal , Fragilidade , Proteínas de Membrana , Idoso , Humanos , Biomarcadores/sangue , Estudos Transversais , Idoso Fragilizado , Fragilidade/sangue , Avaliação Geriátrica/métodos , Vida Independente , Proteínas de Membrana/sangue , Proteínas Adaptadoras de Transdução de Sinal/sangueRESUMO
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aß42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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Doença de Alzheimer , Cadeias HLA-DRB1 , Doença de Parkinson , Humanos , Doença de Alzheimer/genética , Antígenos de Histocompatibilidade , Antígenos HLA , Cadeias HLA-DRB1/genética , Doença de Parkinson/genéticaRESUMO
BACKGROUND: The longevity gene Klotho (KL) was recently associated with neurodegenerative diseases including Alzheimer's disease (AD). Its role in the brain has not been completely elucidated, although evidence suggests that KL-VS heterozygosity is associated with a reduced risk of AD in Apolipoprotein E É4 carriers. Conversely, no data about genetic association with frontotemporal dementia (FTD) are available so far. OBJECTIVE: To investigate the involvement of KL in AD and FTD by the determination of the genetic frequency of KL-VS variant and the expression analysis of KL gene. METHODS: A population consisting of 438 patients and 240 age-matched controls was enrolled for the study. KL-VS and APOE genotypes were assessed by allelic discrimination through a QuantStudio 12K system. KL gene expression analysis was performed in a restricted cohort of patients consisting of 43 AD patients, 41 FTD patients and 19 controls. KL gene expression was assessed in peripheral blood mononuclear cells with specific TaqMan assay. Statistical analysis was performed using GraphPad 9 Prims software. RESULTS: KL-VS frequency was comparable to the ones found in literature and no differences were found in both allelic and genotypic frequencies between patients and controls were found. Conversely, KL expression levels were significantly lower in AD and FTD patients compared with controls (mean fold regulation - 4.286 and - 6.561 versus controls in AD and FTD, respectively, pâ=â0.0037). CONCLUSION: This is the first study investigating KL in FTD. We showed a decreased expression of the gene in AD and FTD, independent of the genotype, suggesting a role of Klotho in common steps during neurodegeneration.
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Doença de Alzheimer , Demência Frontotemporal , Humanos , Doença de Alzheimer/genética , Demência Frontotemporal/genética , Expressão Gênica , Genótipo , Leucócitos MononuclearesRESUMO
Social isolation and feelings of loneliness are related to higher mortality and morbidity. Evidence from studies conducted during space missions, in space analogs, and during the COVID-19 pandemic underline the possible role of the autonomic nervous system in mediating this relation. Indeed, the activation of the sympathetic branch of the autonomic nervous system enhances the cardiovascular response and activates the transcription of pro-inflammatory genes, which leads to a stimulation of inflammatory activation. This response is adaptive in the short term, in that it allows one to cope with a situation perceived as a threat, but in the long term it has detrimental effects on mental and physical health, leading to mood deflection and an increased risk of cardiovascular disease, as well as imbalances in immune system activation. The aim of this narrative review is to present the contributions from space studies and insights from the lockdown period on the relationship between social isolation and autonomic nervous system activation, focusing on cardiovascular impairment and immune imbalance. Knowing the pathophysiological mechanisms underlying this relationship is important as it enables us to structure effective countermeasures for the new challenges that lie ahead: the lengthening of space missions and Mars exploration, the specter of future pandemics, and the aging of the population.
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Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle-brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle-brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle-brain axis is also provided.
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Disfunção Cognitiva , Fragilidade , Sarcopenia , Humanos , Idoso , Músculo Esquelético/metabolismo , Fragilidade/complicações , Envelhecimento/fisiologia , Disfunção Cognitiva/metabolismo , Encéfalo/metabolismoRESUMO
Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
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Centenários , Longevidade , Idoso de 80 Anos ou mais , Humanos , Longevidade/genética , Metilação de DNA , Epigênese Genética/genéticaRESUMO
BACKGROUND: Frailty, defined as physical performance impairment, is a common condition in older adults and can anticipate the development of sarcopenia, a geriatric syndrome characterized by loss of muscle strength and mass. microRNAs (miRNAs) are short molecules of RNA endowed with the ability to modulate gene expression; miRNAs are present in serum and are considered potential biomarkers for several diseases. Serum concentration of miR-451a, miR-93-5p, miR-155-5p, miR-421-3p, miR-425-5p, miR-495-3p and miR-744-5p was recently shown to be altered in sarcopenic patients. METHODS: We verified if a particular miRNAs pattern could be detected in frailty as well by analyzing these molecules in 50 frail and 136 robust subjects. Additionally, a subgroup of these subjects (15 frail and 30 robust) underwent a 12-week program based on a multicomponent exercise protocol (VIVIFRAIL) consisting of resistance training, gait retraining, and balance training. After the program, serum miRNAs concentration was measured again, to verify whether the physical activity had an effect on their concentration. Moreover, clinical characteristics and indicators of physical performance of all subjects were compared before and after intervention to verify the effect of the VIVIFRAIL program. RESULTS: At the end of the multicomponent exercise program, Short Physical Performance Battery (SPPB) score as well right and left handgrip (p < 0.05) were significantly increased in frail subjects; right and left handgrip significantly were increased also in robust subjects (p < 0.05). Interestingly, the variation of SPPB was significantly higher in frail compared to robust subjects (p < 0.0001). Moreover, at the end of the program, in frail compared to robust subjects: miR-451a serum concentration was significantly increased (frail: 6.59 × 104; 1.12 × 104-2.5 × 105 c/ng; robust: 2.31 × 104; 1.94 × 103-2.01 × 105 c/ng) (p < 0.05); and 2) miR-93-5p and miR-495-3p serum concentration was reduced, whereas that of miR-155-5p was significantly increased (p < 0.05 in both cases). Serum concentration of miR-93-5p and miR-495-3p was decreased, and that of miR-155-5p was increased at the end of the program in robust subjects alone, statistical significance being reached for miR-93-5p alone (p = 0.02). CONCLUSION: These results suggest that serum miR-451a should be investigated as a potential biomarker for frailty and show that the VIVIFRAIL multicomponent program modulates circulatory miRNAs expression, at least in older adults.
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Fragilidade , MicroRNAs , Sarcopenia , Humanos , Idoso , Fragilidade/genética , Idoso Fragilizado , Força da Mão , MicroRNAs/genética , Biomarcadores , Exercício FísicoRESUMO
Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians. Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained. Results: Six hundred fifteen individuals (aged 86.4 ± 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (ρs = -0.17 [confidence interval; CI: -0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (ß = -0.44, odds ratio [OR]: 0.64 [CI: 0.47-0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44-0.80] ß = -0.51, p < 0.001]. Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.
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Fragilidade , Tiroxina , Tri-Iodotironina , Feminino , Humanos , Masculino , Biomarcadores , Testes de Função Tireóidea , Hormônios Tireóideos , Tireotropina , Tiroxina/sangue , Tri-Iodotironina/sangue , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Alzheimer's disease (AD) is clinically heterogeneous, including the classical-amnesic (CA-) phenotype and some variants. OBJECTIVE: We aim to describe a further presentation we (re)named confabulation-misidentification (CM-) phenotype. METHODS: We performed a retrospective longitudinal case-series study of 17 AD outpatients with the possible CM-phenotype (CM-ADs). Then, in a cross-sectional study, we compared the CM-ADs to a sample of 30 AD patients with the CA-phenotype (CA-ADs). The primary outcome was the frequency of cognitive and behavioral features. Data were analyzed as differences in percentage by non-parametric Chi Square and mean differences by parametric T-test. RESULTS: Anterograde amnesia (100%) with early confabulation (88.2%), disorientation (88.2%) and non-infrequently retrograde amnesia (64.7%) associated with reduced insight (88.2%), moderate prefrontal executive impairment (94.1%) and attention deficits (82.3%) dominated the CM-phenotype. Neuropsychiatric features with striking misidentification (52.9%), other less-structured delusions (70.6%), and brief hallucinations (64.7%) were present. Marked behavioral disturbances were present early in some patients and very common at later stages. At the baseline, the CM-ADs showed more confabulation (pâ<â0.001), temporal disorientation (pâ<â0.02), misidentification (pâ=â0.013), other delusions (pâ=â0.002), and logorrhea (pâ=â0.004) than the CA-ADs. In addition, more social disinhibition (pâ=â0.018), reduction of insight (pâ=â0.029), and hallucination (pâ=â0.03) persisted at 12 months from baseline. Both the CA- and CM-ADs showed anterior and medial temporal atrophy. Compared to HCs, the CM-ADs showed more right fronto-insular atrophy, while the CA-ADs showed more dorsal parietal, precuneus, and right parietal atrophy. CONCLUSION: We described an AD phenotype resembling diencephalic rather than hippocampal amnesia and overlapping the past-century description of presbyophrenia.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Estudos Retrospectivos , Estudos Transversais , Amnésia/psicologia , Transtornos da Memória , Hipocampo , Alucinações , Confusão , Testes NeuropsicológicosRESUMO
Dysfunctions in liver metabolic activities may increase the risk of cognitive impairment and dementia. In a cohort of community-dwelling older persons investigated for a suspected cognitive decline, we studied the association between liver status and dementia, considering sex and frailty contribution. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and the AST/ALT ratio were used to assess liver function in 419 older adults (248 persons with dementia and 171 age- and sex-matched subjects without cognitive decline). Although the serum concentrations of the liver enzymes were in the physiologic range, patients with dementia showed lower ALT concentrations (p = 0.005) and higher AST/ALT ratios (p = 0.003) compared to controls. The same differences were found when comparing men with and without dementia (ALT, p = 0.009; AST/ALT ratio, p = 0.003) but disappeared in women. Curiously, comparing women and men with the same diagnosis, the ALT concentrations were lower (p = 0.008), and the AST/ALT ratio was higher (p = 0.001) in control women than men, whereas no significant difference was found between persons with dementia. In conclusion, in our cohort of older people living in the community, the association between serum aminotransferases and dementia was remarked. Moreover, our results support attention to sex difference in liver function, suggesting a role in the pathogenesis of dementia.