ABSTRACT
More than one-third of the cases of infective endocarditis (IE) occur in older patients. The disease is often characterized by atypical symptoms. The incidence of neurological complications is high and represents a strong independent predictor of severe outcomes and mortality. IE is a rare but serious complication of transcatheter aortic valve implantation (TAVI). A persistent delirium as a unique manifestation of post-TAVI IE in an older patient is presented in this clinical case.
Subject(s)
Aortic Valve Stenosis , Delirium , Endocarditis, Bacterial , Endocarditis , Prosthesis-Related Infections , Transcatheter Aortic Valve Replacement , Humans , Aged , Transcatheter Aortic Valve Replacement/adverse effects , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiology , Endocarditis/etiology , Endocarditis/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/etiology , Delirium/etiology , Delirium/complications , Aortic Valve Stenosis/surgery , Aortic Valve , Treatment Outcome , Risk FactorsABSTRACT
Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disease, causing motor and cognitive dysfunction and dementia. iNPH and Alzheimer's disease (AD) share similar molecular characteristics, including amyloid deposition, t-tau and p-tau dysregulation; however, the disease is under-diagnosed and under-treated. The aim was to identify a panel of sphingolipids and proteins in CSF to diagnose iNPH at onset compared to aged subjects with cognitive integrity (C) and AD patients by adopting multiple reaction monitoring mass spectrometry (MRM-MS) for sphingolipid quantitative assessment and advanced high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic analysis. The results indicated that iNPH are characterized by an increase in very long chains Cer C22:0, Cer C24:0 and Cer C24:1 and of acute-phase proteins, immunoglobulins and complement component fragments. Proteins involved in synaptic signaling, axogenesis, including BACE1, APP, SEZ6L and SEZ6L2; secretory proteins (CHGA, SCG3 and VGF); glycosylation proteins (POMGNT1 and DAG1); and proteins involved in lipid metabolism (APOH and LCAT) were statistically lower in iNPH. In conclusion, at the disease onset, several factors contribute to maintaining cell homeostasis, and the protective role of very long chains sphingolipids counteract overexpression of amyloidogenic and neurotoxic proteins. Monitoring specific very long chain Cers will improve the early diagnosis and can promote patient follow-up.
Subject(s)
Hydrocephalus, Normal Pressure/cerebrospinal fluid , Nerve Tissue Proteins/cerebrospinal fluid , Proteomics , Aged , Aged, 80 and over , Biomarkers/cerebrospinal fluid , Female , Humans , Male , Middle Aged , Sphingolipids/cerebrospinal fluidABSTRACT
PURPOSE: Advancing age represents the strongest risk factor for Alzheimer's disease (AD), and the identification of biomarkers able to define what characterizes physiological aging from AD may represent a potential starting point for novel preventive strategies. Among these biomarkers, telomeres seem to be a promising target. Interestingly, high intake of carotenoid-rich food may play a role in protecting telomeres by oxidative stress reduction. Accordingly, low plasma ß-carotene concentrations have been found in AD subjects when compared with cognitively healthy subjects. In this study, we aim at investigating the hypothesis that low ß-carotene might be associated with markers of accelerated cellular aging, including leucocyte telomere length (LTL) and peripheral mononuclear cell (PBMC) telomerase activity in a cohort of old age subjects. METHODS: The study was conducted in 68 old age subjects, 37 AD, and 31 age-matched healthy controls. In all subjects, ß-carotene plasma level, LTL and peripheral telomerase activity were measured. RESULTS: In all populations, ß-carotene significantly and positively (r = 0.320, p = 0.008) correlated with telomerase activity, independent of gender. A model having telomerase activity levels as the dependent variable, and age, gender, smoking habit, and ß-carotene as independent variables, confirmed that ß-carotene was independently associated with telomerase activity (ß = 0.319, p = 0.012). Subjects affected by AD had significantly lower plasmatic levels of ß-carotene (448 ± 66 mg/ml vs 497 ± 59 mg/ml, p = 0.001) and LTL (0.53 ± 0.25 vs 0.69 ± 0.29; p = 0.009) as compared with healthy controls. Β-carotene plasma level was associated with AD diagnosis (OR 0.988; IC95% 0.978-0.997; p = 0.013) independently of age, gender, smoking habit, ApoE genotype, and LTL. CONCLUSION: Our data show that ß-carotene may modulate telomerase activity in old age. Moreover, lower plasma ß-carotene levels, correlating with peripheral telomerase activity, are associated with AD diagnosis independent of multiple covariates.
Subject(s)
Alzheimer Disease/blood , Geriatric Assessment/methods , Telomerase/blood , beta Carotene/blood , Aged , Aged, 80 and over , Biomarkers/blood , Cross-Sectional Studies , Female , Humans , MaleABSTRACT
BACKGROUND: Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer's disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects. AIM: Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD. METHODS: 53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, ß-, γ- and δ-tocopherol, α-, ß-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured. RESULTS AND DISCUSSION: Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, ß-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and ß-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging. CONCLUSIONS: Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.
Subject(s)
Alzheimer Disease/blood , Telomere Homeostasis , Vitamin E/blood , Biomarkers/blood , Case-Control Studies , Cellular Senescence , Cohort Studies , Disease Progression , Female , Humans , Male , Oxidative StressABSTRACT
Confabulation may be present in Alzheimer's disease (AD), but usually it is not a primary feature of either its typical or atypical variants. In this report, we describe the case of an AD patient who showed an unusual and enduring neuropsychiatric phenotype characterized by early and prominent spontaneous confabulation. Surprisingly, such atypical AD presentation bears a striking resemblance to presbyophrenia, a subtype of dementia which was described at the beginning of the twentieth century and then sank into oblivion. In discussion, we speculate on the "return" of presbyophrenia as an unrecognized neuropsychiatric variant of AD and its possible neuroanatomical substrates.
Subject(s)
Activities of Daily Living/psychology , Alzheimer Disease/complications , Alzheimer Disease/psychology , Cognitive Dysfunction/etiology , Aged , Caregivers/psychology , Female , Follow-Up Studies , Humans , Memory Disorders/etiologySubject(s)
Anisocoria , Cognitive Dysfunction , Anisocoria/diagnosis , Cognitive Dysfunction/diagnosis , HumansABSTRACT
We describe a family composed of six siblings, four of which affected by late-onset Alzheimer's disease (LOAD). We constructed the family pedigree, evaluated mutations usually associated with early-onset Alzheimer's disease (APP, PSEN1, PSEN2), and assessed polymorphisms in the apolipoprotein E (APOE) gene and in cytokine genes that we had previously found to be associated with a higher risk of LOAD (IL-10, IL-6, TNF-α). Results showed that all subjects carried one ε4 allele of the APOE gene and those with the earliest age of onset exhibited the AA (-1082) IL-10 and the CC (-174) IL-6 genotypes. The only male had a genetic profile which also included the A (-308) TNF-α allele. These data confirm the role of the APOE gene as genetic risk factor in LOAD, and suggest that the risk of developing AD may be governed by a "susceptibility profile" involving polymorphisms in inflammatory genes.
Subject(s)
Alzheimer Disease/genetics , Dementia/genetics , Siblings , Aged , Aged, 80 and over , Alleles , Female , Genotype , Humans , Italy , Male , Polymorphism, GeneticABSTRACT
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.
Subject(s)
Adaptor Proteins, Signal Transducing , Frailty , Membrane Proteins , Aged , Humans , Biomarkers/blood , Cross-Sectional Studies , Frail Elderly , Frailty/blood , Geriatric Assessment/methods , Independent Living , Membrane Proteins/blood , Adaptor Proteins, Signal Transducing/bloodABSTRACT
Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty's contribution. Our cohort included 509 adults, aged 64-92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer's Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.
Subject(s)
Cognitive Dysfunction , Frailty , Aged , Aged, 80 and over , Frail Elderly/psychology , Humans , Middle Aged , Vitamin D , VitaminsABSTRACT
Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer's Disease (AD). The 26 bp intergenic polymorphism of VAMP2, a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated ApoE4 and VAMP2 26 bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as VAMP2 gene expression in a subset of 73 AD, 122 MD, 103 MCI and 140 CT. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time. VAMP2 mRNA was higher in MD compared to AD (p = 0.0013) and CT (p = 0.0017), and in MCI-MD compared to MCI-AD (p < 0.001) after correcting for age, gender, MMSE and ApoE4 +/- covariates (p c = 0.004). A higher VAMP2 expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (p = 0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (p c = 0.036). These results suggest that VAMP2 mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients.
ABSTRACT
OBJECTIVES: Psycholeptic drugs have been used in the older population for years, especially to control delirium and neuropsychiatric symptoms (NPS) of dementia. However, data from the literature confirm that the prolonged use of psycholeptics may be responsible for adverse reactions in older patients. The aim of this study was (1) to identify how many patients receive the first prescription of a psycholeptic drug during the hospital stay; (2) to evaluate the main sociodemographic and clinical characteristics of these patients; and (3) to verify if the prescribed psycholeptic drugs are continued after 3 months from the hospital discharge. DESIGN: Our retrospective study was based on data from the REPOSI (REgistro POliterapie SIMI) registry, a cohort of older patients hospitalized in internal medicine and geriatric wards throughout Italy from 2010 to 2018. SETTING AND PARTICIPANTS: Patients aged 65 years or older who were not on home therapy with psycholeptic drugs were considered in the analyses. METHODS: We did both univariate and multivariate analyses in order to find the variables associated independently to an increased risk for first psycholeptic prescription at hospital discharge. RESULTS: At hospital discharge, 193 patients (5.8%) out of a total sample of 3322 patients were prescribed at least 1 psycholeptic drug. Cognitive impairment was the main risk factor for the introduction of psycholeptic drugs at discharge. Among them, 89.1% were still on therapy with a psycholeptic drug after 3 months from the hospital discharge. CONCLUSIONS AND IMPLICATIONS: Cognitive impairment represents the main risk factor for psycholeptic initiation in hospitalized older patients. The vast majority of these treatments are chronically continued after the discharge. Therefore, special attention is needed in prescribing psycholeptics at discharge, because their prolonged use may lead to cognitive decline. Moreover, their continued use should be questioned by physicians providing post-acute care, and deprescribing should be considered.
Subject(s)
Hospitalization , Patient Discharge , Aged , Humans , Italy , Length of Stay , Retrospective StudiesABSTRACT
Microglia performs a variety of functions during brain development designed to maintain brain homeostasis. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in microglial cells modulating phagocytosis, cytokine production, cell proliferation, and cell survival. Interestingly, the levels of soluble TREM2 (the secreted ectodomain of TREM2, sTREM2) were higher in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients than subjects without cognitive decline. It is noteworthy that, while CSF sTREM2 levels have been extensively studied, few studies have investigated sTREM2 in blood producing conflicting results. We aimed to investigate the levels of sTREM2 in CSF and blood from a cohort of well-characterized AD comparing the results to those obtained in patients suffering from idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cognitive impairment. Our findings underlined a significantly lower plasma sTREM2 concentration in AD patients compared to iNPH subjects [39.1 ng/mL (standard deviation (SD), 15.0) and 47.2 ng/mL (SD, 19.5), respectively; p = 0.01], whereas no difference was revealed between the two groups in the CSF sTREM2 levels. The adjusted regression analyses evidenced in AD patients an association between plasma and CSF sTREM2 levels [B = 0.411; 95% confidence interval (CI), 0.137-0.685, p = 0.004], as well as ß-amyloid concentrations (B = 0.035; 95% CI, 0.007-0.063, p = 0.01) and an association between CSF sTREM2 and phospho-Tau concentrations (B = 0.248; 95% CI, 0.053-0.443; p = 0.01). No significant relation was found in iNPH patients. In conclusion, these differences in sTREM2 profiles between AD and iNPH reinforce the notion that this receptor has a role in neurodegeneration.
Subject(s)
Electronic Health Records , Information Technology , Humans , Aged , Medical History Taking , Delivery of Health CareABSTRACT
OBJECTIVES: To evaluate the effects of repeated cerebrospinal fluid (CSF) tap procedures in idiopathic normal pressure hydrocephalus (iNPH) patients ineligible for surgical treatment. DESIGN: Prospective, monocentric, pilot study. SETTING: University hospital. PARTICIPANTS: Thirty-nine patients aged 75 years and older, ineligible for shunting surgical intervention. INTERVENTION: Repeated CSF taps. MEASUREMENTS: All patients underwent a comprehensive geriatric assessment before and after each CSF tap. Adverse events were recorded. RESULTS: No major side effect was reported. Eleven patients showed no response to the first CSF tap test and were excluded. In the remaining 28 patients, all physical and cognitive functions improved after the drainage procedures, except for continence (which seemed poorly influenced). According to clinical judgment, the mean time frame of benefit between CSF taps was 7 months. Patients withdrawing from the protocol during the clinical follow-up showed a worsening of functional and cognitive performances after the interruption. CONCLUSIONS/IMPLICATIONS: Periodic CSF therapeutic taps are safe, allow a better control of iNPH symptoms, and prevent functional decline in geriatric patients.
Subject(s)
Hydrocephalus, Normal Pressure/cerebrospinal fluid , Reoperation , Spinal Puncture/methods , Aged , Aged, 80 and over , Cognition , Female , Humans , Male , Pilot Projects , Prospective StudiesABSTRACT
BACKGROUND: Ultra-micronized palmitoylethanolamide (um-PEA) represents an attractive option for chronic pain control in complex older patients at higher risk of adverse effects with traditional analgesics. OBJECTIVE: The aim of this study was to determine the effectiveness of um-PEA versus placebo on chronic pain intensity and function in individual geriatric patients. DESIGN: We performed randomized, blinded N-of-1 trials with two 3-week um-PEA versus placebo comparisons, separated by 2-week washout periods. PARTICIPANTS: The study included outpatients aged ≥ 65 years with chronic, non-cancer, non-ischemic pain in the back, joints, or limbs. INTERVENTION: Patients were randomized to Um-PEA 600 mg or placebo twice daily. MEASUREMENTS: Pain intensity was measured using an 11-point visual numeric scale. Functional impairment was measured using a Back Pain Functional Scale. Impact of each N-of-1 trial was measured on the clinician's intention to treat and confidence. RESULTS: Ten of 11 eligible patients consented over 7 months [all female, mean age 83.2 years (SD 4.6)]. Three patients interrupted the trial: one had diarrhea (under placebo), one for low adherence, and one for intercurrent pneumonia. A small statistically significant effect in favor of um-PEA was seen at the mixed method analyses in two patients (effect size equal to 8% of the baseline pain). A statistically significant impact on function was found in one patient. After the trial, um-PEA was prescribed to four patients; in two patients the clinician changed their pre-trial intention to treat; the clinician confidence in the treatment plan either increased (5) or remained the same (2). CONCLUSIONS: Our experience confirmed that N-of-1 trials may help make personalized evidence-based decisions in complex older patients, with special feasibility considerations. CLINICALTRIALS.GOV: NCT02699281.
Subject(s)
Analgesics/administration & dosage , Chronic Pain/drug therapy , Ethanolamines/administration & dosage , Palmitic Acids/administration & dosage , Aged , Aged, 80 and over , Amides , Female , Geriatric Assessment , Humans , Male , Pilot ProjectsABSTRACT
BACKGROUND: Chronic pain in older people is highly prevalent, often underestimated, and associated with adverse outcomes. Most available analgesic drugs are often either ineffective or not tolerated, with many side effects. Palmitoylethanolamide (PEA) is an endogenous widely distributed N-acylethanolamina involved in neuroinflammation and pain-generating processes. Formulations containing ultra-micronized palmitoylethanolamide (um-PEA) are available but their effectiveness on chronic pain in highly heterogeneous geriatric patients is not clear and probably not generalizable. We planned to adopt the N-of-1 trial approach to test the effectiveness of um-PEA objectively at the individual level in our older outpatients. METHODS/DESIGN: Persons 65 years or older referring to the Geriatric Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan complaining of noncancer chronic pain of any origin will be eligible. Each trial will be a placebo-controlled randomized crossover trial including two um-PEA (600 mg twice a day) and placebo treatment pairs. The um-PEA or placebo 3-week periods will be separated by 2-week washout intervals to overcome possible carryover effects. Pain intensity, need of on-demand analgesic medications, and impact on daily activities will be evaluated. Cognitively impaired patients will be eligible as long as an expression of pain can be recognized and its frequency assessed by a caregiver. Trial results will be discussed with the patient or caregiver and the treating physician to decide whether to continue the treatment. The impact of the N-of-1 approach on the physician's management plan and confidence will be assessed. We will secondarily meta-analyze the performed N-of-1 trials to obtain an estimate of the average effect of um-PEA compared with placebo using a frequentist and Bayesian approach. DISCUSSION: While pursuing an ultimate clinical objective, i.e. to empirically and objectively decide the best treatment choice for an individual older patient with chronic pain, these series of geriatric N-of-1 trials on PEA will bring the principles of evidence-based medicine into the care of patients not usually represented in conventional randomized controlled trials, and realize a patient-centered outcome approach necessary to improve appropriate prescribing in elderly patients with multimorbidity and polypharmacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02699281 . Registered on 3 March 2016.
Subject(s)
Analgesics/administration & dosage , Chronic Pain/drug therapy , Clinical Protocols , Ethanolamines/administration & dosage , Palmitic Acids/administration & dosage , Aged , Amides , Bayes Theorem , Cross-Over Studies , Humans , Sample SizeABSTRACT
BACKGROUND: Clinical events occurring during hospital stay are independent predictors of prolonged hospitalization, in-hospital mortality and readmission among elderly patients admitted to medical wards. PURPOSE: To identify predictors of intercurrent clinical events (ICE) during hospital stay among the main demographic, functional and clinical characteristics assessed at hospital admission in a multicenter sample of elderly inpatients in Italy. METHODS: This observational prospective cohort study was conducted in 66 internal and geriatric medicine hospital wards in 2010. It enrolled 1267 inpatients aged 65years or older living at home before hospitalization. Multivariable Poisson regression analyses were employed to identify the most common ICEs as well as their independent predictors. RESULTS: During the hospital stay 427 patients (33.7%) experienced at least one ICE. The most common ICEs were urinary tract infections, pneumonia, anemia, arrhythmias and fluid electrolyte disorders. After correction for age, sex, comorbidity, cognitive impairment and functional dependence, independent predictors of any ICE were: being a bladder catheter holder (RR [risk ratio] 1.86, 95% CI 1.52-2.27), being on treatment at home with a proton pump inhibitor (PPI) (RR 1.25, 95% CI 1.03-1.53), with immunosuppressant therapy (RR 2.10, 95% CI 1.24-3.56), and body temperature at admission (RR 1.19, 95% CI 1.06-1.33). CONCLUSION: Four clinical characteristics, easily assessable at admission, may be useful to identify elderly inpatients at a higher risk for developing ICEs during hospital stay. Furthermore three of these predictors are modifiable factors, thus interventions reducing the use of catheter, PPI and immunosuppressants may result in reduction of ICEs.
Subject(s)
Anemia/epidemiology , Arrhythmias, Cardiac/epidemiology , Hospitalization , Pneumonia/epidemiology , Urinary Tract Infections/epidemiology , Water-Electrolyte Imbalance/epidemiology , Aged , Aged, 80 and over , Body Temperature , Female , Fever/epidemiology , Humans , Immunosuppressive Agents/therapeutic use , Italy/epidemiology , Male , Multivariate Analysis , Odds Ratio , Poisson Distribution , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Risk Assessment , Risk Factors , Urinary Catheterization/statistics & numerical dataABSTRACT
Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disease that usually develops in the elderly. Natural history of iNPH is still unknown. It has been hypothesized that cerebrovascular diseases could have a role in etiology of chronic hydrocephalus and studies show an increased prevalence of cardiovascular diseases in iNPH patients. Moreover, evidences show a possible alteration of immune system in iNPH patients. Adenosine (Ado) is a metabolite produced in response to metabolic stress and injury. Adenosine and its receptors play an important role in vascular protection and in the modulation of inflammatory reactions and neuroinflammation. Our aim is to evaluate gene and protein expression of A1R and A2AR in the peripheral blood mononuclear cells (PBMCs) from iNPH patients compared to control subjects. We investigate if Ado system, that plays an important role in central nervous system, in vascular system, and also in inflammation, is involved in pathophysiology of iNPH disease. Our analysis showed that A1R mRNA levels and A1R density in PBMCs from iNPH patients were significantly lower than CT subjects (0.84 ± 0.12 and 2.42 ± 0.42, p<0.001 and 0.31 ± 0.02 and 0.42 ± 0.04, p=0.043; respectively). About A2AR, the gene expression in PBMCs was significantly lower in iNPH than CT (0.65 ± 0.09 and 1.5 ± 0.14, p<0.001) as well as there was a trend in protein expression: iNPH and CT (0.51 ± 0.05 and 0.62 ± 0.03; p=0.172). This preliminary study underlines the involvement of Ado system in iNPH disease whose pathophysiology is still unclear.
Subject(s)
Down-Regulation , Hydrocephalus, Normal Pressure/metabolism , Leukocytes, Mononuclear/metabolism , Receptor, Adenosine A1/metabolism , Receptor, Adenosine A2A/metabolism , Aged , Aged, 80 and over , Female , Humans , Hydrocephalus, Normal Pressure/genetics , Male , Receptor, Adenosine A1/genetics , Receptor, Adenosine A2A/geneticsABSTRACT
As the European population gets older, the incidence of neurological disorders increases with significant impact on social costs. Despite differences in disease etiology, several brain disorders in the elderly (e.g., Alzheimer's disease, vascular dementia, normal pressure hydrocephalus) share dementia as a common clinical feature. The current treatment for the majority of these diseases is merely symptomatic and does not modify the course of the illness. Symptoms of normal pressure hydrocephalus are the only ones that can be modified if they are recognized in time and treated appropriately. Therefore, an important clinical strategy may be disclosed by pathogenic pathways that can be modified and to find drugs that can slow down or even arrest disease progression. Possibly a way to answer this question could be by re-examining all the molecules which have so far succeeded in improving many aspects of cognitive deterioration in some neurodegenerative conditions, that were not considered because of controversial opinions. The main purpose of this summary is to further substantiate the hypothesis that the pathway of adenosine type A2A receptor could be used as a potential target to develop new/old therapeutic strategies.