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1.
Dement Geriatr Cogn Disord ; 46(3-4): 140-153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30199883

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the prognostic power of late-life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for the onset of Alzheimer's disease (AD) within 4 years of follow-up. METHODS: We estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients suffering of LLD treated with antidepressants with good compliance, and 66 healthy control (HC) patients, followed for 4 years. RESULTS: The risk to develop AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60% deteriorated without depression, and 72.20% deteriorated with depression after 4 years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other dementia type. CONCLUSION: In our results, aMCI was the first predictive condition that increased the risk to develop AD. Depression is a potentially preventable medical condition across the lifespan and may be a modifiable risk factor.


Assuntos
Disfunção Cognitiva/diagnóstico , Depressão/diagnóstico , Transtornos da Memória/diagnóstico , Testes Neuropsicológicos , Idade de Início , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Antidepressivos/uso terapêutico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Depressão/tratamento farmacológico , Depressão/epidemiologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco
2.
Int J Geriatr Psychiatry ; 30(9): 965-75, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25504466

RESUMO

OBJECTIVE: To evaluate in a pilot single-blind randomized controlled clinical trial the efficacy of an integrated treatment with rivastigmine transdermal patch (RTP) and cognitive stimulation (CS) in Alzheimer's disease (AD) patients at 6-month follow-up. METHODS: We enrolled 90 patients with an age ≥65 years admitted to the outpatient Alzheimer's Evaluation Unit with diagnosis of AD. Patients were randomized to enter in the Group-1 (RTP + CS) or in the Group-2 (RTP). All patients at baseline and after 6 months were evaluated with the following tools: Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression (HAM-D), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-Distress (NPI-D), and a standardized Comprehensive Geriatric Assessment, including also activities of daily living (ADL), instrumental activities of daily living (IADL), and the Mini Nutritional Assessment (MNA). Mortality risk was assessed using the Multidimensional Prognostic Index (MPI). RESULTS: At baseline no significant difference was shown between the two groups. After 6 months of follow-up, there were significant differences between Group-1 and Group-2 in: MMSE: +6.39% vs. +2.69%, CDR: +6.92% vs. +1.54%, HDRS-D = -60.7% vs. -45.8%, GDS: -60.9% vs. -7.3%, NPI: -55.2% vs. -32.7%%, NPI-D: -55.1% vs. -18.6%, ADL: +13.88% vs. +5.95%, IADL: +67.59% vs. +18.28%, MNA: +12.02% vs. +5.91%, and MPI: -29.03% vs. -12.90%. CONCLUSION: The integrated treatment of RTP with CS in AD patients for 6 months improved significantly cognition, depressive and neuropsychiatric symptoms, functional status, and mortality risk in comparison with a group of AD patients receiving only RTP.


Assuntos
Doença de Alzheimer/terapia , Terapia Cognitivo-Comportamental , Fármacos Neuroprotetores/uso terapêutico , Rivastigmina/uso terapêutico , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/mortalidade , Doença de Alzheimer/psicologia , Terapia Combinada , Feminino , Seguimentos , Avaliação Geriátrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Projetos Piloto , Escalas de Graduação Psiquiátrica , Fatores de Risco , Rivastigmina/administração & dosagem , Adesivo Transdérmico
3.
Int J Geriatr Psychiatry ; 30(9): 891-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25475248

RESUMO

OBJECTIVE: To characterize the differences of caregiver burden in patients with Alzheimer's disease (AD) and vascular dementia (VaD) in order to improve the care counselling and management plan. METHODS: We included 506 patients consecutively attending the Alzheimer's Evaluation Unit of a Geriatric Unit, evaluated with Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression, and Neuropsychiatric Inventory. To all caregivers were administered the Caregiver Burden Inventory (CBI), a 24-item multidimensional questionnaire in which 5 subscales explore 5 dimensions of caregiver burden: (1) CBI-Objective; (2) CBI-Developmental; (3) CBI-Physical; (4) CBI-Social; and (5) CBI-Emotional. RESULTS: The present study included, respectively, 253 AD patients and 253 VaD patients. AD patients at baseline showed a significantly higher instruction level (p < .0001), higher grade of cognitive impairment (MMSE, p < .0001), and increased severity stage of dementia (CDR, p < .0001) than VaD patients. AD caregivers, mainly females (p = 0.010), devoted significantly more length of time care (in months, p = 0.010) and time of daily care (in hours, p = 0.011) and showed a significantly higher burden level in CBI-Objective (p = 0.047), CBI-Physical (p < .0001), CBI-Social (p = 0.003), CBI-Emotional (p < .0001), and CBI-total score (p < .0001), than VaD caregivers. In both caregiver groups, a higher presence of spouses and sons (p < .0001) compared to other relatives was observed. AD caregiver burden showed a significant association with sex of caregivers and length of time care in months. CONCLUSIONS: AD caregivers showed a higher burden level than VaD caregivers, and this appeared to be associated with sex and length of time care.


Assuntos
Doença de Alzheimer/enfermagem , Cuidadores/psicologia , Demência Vascular/enfermagem , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Análise de Variância , Efeitos Psicossociais da Doença , Aconselhamento/normas , Demência Vascular/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica
4.
Am J Geriatr Psychiatry ; 21(1): 67-77, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23290204

RESUMO

OBJECTIVE: Polymorphism C in the solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) gene has been variously associated with major depressive disorder (MDD). To the best of our knowledge, no data were reported regarding a role of SLC6A4 in late-life MDD. The aim of this study was to explore the possible involvement of the SLC6A4 locus in patients with late-life MDD by means of a haplotype-tagged approach. DESIGN: Case-control study. SETTING: Older patients attending a geriatric unit. PARTICIPANTS: A total of 218 patients with late-life MDD (61 men and 157 women) age 65 to 92 years (76.29 ± 6.53 years) and 363 depression-free healthy subjects (156 men and 207 women) age 41 to 65 years (48.33 ± 5.94 years). MEASUREMENTS: Genotyping and haplotype estimation of the three markers rs4795541, rs140701, and rs3813034 spanning a 39-kb block the SLC6A4 locus. Diagnoses of late-life MDD, mild cognitive impairment, Alzheimer disease, vascular dementia, and other dementing diseases were made using current clinical criteria. RESULTS: No significant differences were observed in allele or genotype distribution for the three SLC6A4 markers across the study groups. Because the comparison group could not be matched for age, a sensitivity analysis for the misclassification of controls was performed according to different scenarios. For each simulated scenario, the same nonsignificant result was observed. However, the results are limited to late-life MDD that is specifically not associated with cognitive impairment, and there was limited power for detecting very small effect sizes. CONCLUSIONS: Our findings suggested that the SLC6A4 locus play a minor role, if any, in the pathogenesis of late-life MDD. Also, tempering our conclusions, we were unable to account for population stratification, recurrence or chronicity of depression, nor the influence of coexisting medical, cognitive, and psychosocial stressors.


Assuntos
Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Estudos de Casos e Controles , Disfunção Cognitiva/genética , Demência/genética , Demência Vascular , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética
5.
J Clin Med ; 12(14)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37510946

RESUMO

BACKGROUND: The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. METHODS: In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. RESULTS: Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). CONCLUSIONS: The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

6.
Biomedicines ; 10(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35740403

RESUMO

Our study aims to investigate the relationship between medial temporal lobe atrophy (MTA) score, assessed by computed tomography (CT) scans, and functional impairment, cognitive deficit, and psycho-behavioral disorder severity. Overall, 239 (M = 92, F = 147; mean age of 79.3 ± 6.8 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. MTA was evaluated from 0 (no atrophy) to 4 (severe atrophy). The homocysteine serum was set to two levels: between 0 and 10 µmol/L, and >10 µmol/L. The cholesterol and glycemia blood concentrations were measured. Hypertension and atrial fibrillation presence/absence were collected. A total of 14 patients were MTA 0, 44 patients were MTA 1, 63 patients were MTA 2, 79 patients were MTA 3, and 39 patients were MTA 4. Cognitive (p < 0.0001) and functional (p < 0.0001) parameters decreased according to the MTA severity. According to the diagnosis distribution, AD patient percentages increased by MTA severity (p < 0.0001). In addition, the homocysteine levels increased according to MTA severity (p < 0.0001). Depression (p < 0.0001) and anxiety (p = 0.001) increased according to MTA severity. This study encourages and supports the potential role of MTA score and CT scan in the field of neurodegenerative disorder research and diagnosis.

7.
Pharmacogenet Genomics ; 21(4): 225-30, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20859244

RESUMO

OBJECTIVE: Cytochrome P450 (CYP) 2D6 enzyme is the major responsible for the metabolism of donepezil, an inhibitor of acetyl cholinesterase currently used for the symptomatic treatment of mild-to-moderate Alzheimer's disease (AD). Functional polymorphisms in the CYP2D6 gene may affect enzyme activity and thus, the metabolism of donepezil. The aim of this study was to evaluate the effect of 16 functional polymorphisms in the CYP2D6 gene on the clinical response to donepezil treatment in patients with mild-to-moderate AD. METHODS: In this multicenter prospective cohort study we evaluated 57 unrelated Caucasians clinically diagnosed as AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil (5-10 mg/daily) for 6 months. The response to donepezil treatment was evaluated at 6-month follow-up according to the National Institute for Health and Clinical Excellence requirements. The identification of 16 clinically relevant CYP2D6 gene variants was performed by a high-throughput genetic analysis. RESULTS: Thirty-eight of 57 patients (67%) were responders and 19 patients (33%) were nonresponders to donepezil treatment. A significantly higher frequency of gene variants conferring decreased or absent enzyme activity was observed in responder than in nonresponder patients (73.68% vs. 36.84%; P=0.005). The presence of gene variants conferring decreased or absent activity of the CYP2D6 enzyme was significantly associated with a clinical response to donepezil treatment (odds ratio=6.286; 95% confidence interval=1.828-21.667). CONCLUSIONS: Functional polymorphisms in the CYP2D6 gene can influence the clinical efficacy of donepezil. The analysis of CYP2D6 genotypes may be useful in identifying subgroups of AD patients with different clinical response to donepezil treatment.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Citocromo P-450 CYP2D6/genética , Indanos/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Polimorfismo Genético/genética , Doença de Alzheimer/genética , Estudos de Coortes , Donepezila , Feminino , Variação Genética , Humanos , Masculino
8.
Int J Geriatr Psychiatry ; 26(10): 1062-70, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21905100

RESUMO

BACKGROUND: Neuropsychiatric symptoms (NPS) are a common feature of Alzheimer's disease (AD), resulting in particular AD endophenotypes. The common AD genetic risk factor apolipoprotein E (APOE) has been suggested underlying these AD endophenotypes. METHODS: APOE genotyping, a comprehensive geriatric assessment (CGA), and Neuropsychiatric Inventory were performed on 322 consecutive older patients. Patients were divided into three groups: AD with NPS (N = 93), AD without NPS (N = 108), and, as a control group, patients with no cognitive impairment (NoCI: N = 121). Patients with NPS were further sub-divided in four groups according to the European Alzheimer's Disease Consortium (EADC) classification of neuropsychiatric syndromes in AD: hyperactive, psychotic, affective, and apathetic. RESULTS: AD patients with NPS showed a significantly higher grade of cognitive impairment, more severity stage of dementia, more disability in the activities of daily living (ADL), and the instrumental ADL than AD patients without NPS. As expected, an higher frequency of APOE ε3/ε4 genotype was observed in patients with AD, both with and without NPS, than patients with NoCI. No difference in the distribution of APOE genotypes was found between AD patients with vs. without NPS. However, in AD patients APOE ε4-carriers, there was an increased risk of affective [odds ratio (OR): 2.34, 95% confidence interval (CI): 1.19-4.58) and apathetic (OR: 2.24,95%CI: 1.19-4.22) syndromes. CONCLUSIONS: These findings did not suggest a significant association between APOE polymorphism and presence of NPS in AD patients. In AD patients with NPS, however, APOE ε4-carrier status was associated with an increased risk of affective and apathetic syndromes.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Apolipoproteínas E/genética , Polimorfismo Genético , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Razão de Chances , Escalas de Graduação Psiquiátrica , Fatores de Risco
9.
J Alzheimers Dis ; 82(1): 235-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057086

RESUMO

BACKGROUND: Alzheimer's disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. OBJECTIVE: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. METHODS: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10µmol/L and > 10µmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. RESULTS: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p < 0.0001), than MCI and mild dementia. Poss-AD and VaD had a higher frequency of homocysteine > 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p < 0.0001), and functional impairment severity respectively for ADL (p < 0.0001) and IADL (p < 0.0001). CONCLUSION: Higher homocysteine level seems to be significantly related to cognitive impairment frequency and severity, possible AD and VaD, neuropsychiatric symptom severity, and functional impairment severity.


Assuntos
Atividades Cotidianas , Doença de Alzheimer/sangue , Escalas de Graduação Psiquiátrica Breve/estatística & dados numéricos , Disfunção Cognitiva/sangue , Demência Vascular/sangue , Homocisteína/sangue , Idoso , Feminino , Humanos , Entrevistas como Assunto , Masculino
10.
Dement Geriatr Cogn Disord ; 29(5): 424-31, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20502016

RESUMO

BACKGROUND: Genotypes of the solute carrier family 6 (neurotransmitter transporter, serotonin) member 4 (SLC6A4) have been variously associated with depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD). AIMS: To evaluate the possible involvement of different SLC6A4 genotypes/haplotypes in VaD. METHODS: The analysis of the 3 markers rs3813034, rs140701 and rs4795541 spanning the SLC6A4 locus was made in 541 consecutive patients clinically diagnosed as having VaD (n = 372) or no cognitive impairment (n = 169) attending a geriatric ward. A community-dwelling sample of 353 healthy subjects, as a reference for the genetic frequencies in the recruitment area, was also included in the study. All patients and subjects were free from any symptoms of depression, obsessive-compulsive disorder and anxiety. A complete neuroimaging documentation was available for all patients. RESULTS: No important differences were observed in genotype distribution across the study groups. Similarly, no important differences were observed in haplotype distribution when a 3-point analysis was made. CONCLUSION: Our findings suggest that polymorphism C in the promoter region of the SLC6A4 gene plays a minor role, if any, in the pathogenesis of VaD.


Assuntos
Demência Vascular/genética , Depressão/genética , Polimorfismo Genético/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , DNA/genética , Demência Vascular/diagnóstico , Demência Vascular/psicologia , Depressão/psicologia , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica
11.
Transl Neurodegener ; 8: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733861

RESUMO

BACKGROUND: Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. METHODS: We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. RESULTS: Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121-0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522-0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195-4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD. CONCLUSIONS: More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.

12.
Rejuvenation Res ; 11(1): 151-61, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18173367

RESUMO

Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and information on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0-0.33; moderate risk, 0.34-0.66; and severe risk, 0.67-1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 +/- 0.09 and 0.18 +/- 0.09); 31.2 and 30.6% in the moderate-risk group (0.48 +/- 0.09 and 0.49 +/- 0.09); 15.4 and 14.2% in the severe-risk group (0.77 +/- 0.08 and 0.75 +/- 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70-0.80) at 6 months and 0.751 (95%CI, 0.71-0.80) at 1 year of follow-up. We conclude that this MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality.


Assuntos
Avaliação Geriátrica/métodos , Indicadores Básicos de Saúde , Hospitalização , Mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Modelos Teóricos , Prognóstico , Fatores de Tempo
13.
Neurosci Lett ; 438(3): 335-9, 2008 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-18490109

RESUMO

The promoter region of the serotonin transporter gene (SLC6A4) shows a 22-bp tandem repeat polymorphism, indicated as polymorphism C, that has been associated to depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding its association with Alzheimer's disease (AD). No data were reported regarding its association with questionable dementia (QD). In this study we investigate for polymorphism C in the SLC6A4 gene 302 elderly subjects with a clinical diagnosis of AD (n=105), QD (n=88) and no cognitive impairment (n=114) attending a geriatric ward. A community-dwelling sample of 390 healthy subjects was also included in the analysis. A significant higher prevalence of the C16/C16 genotype in AD than in QD was observed (37.14% vs. 3%; p=0.041, OR 2.001, 95%CI 1.018-4.024), while no differences in the C16/C14 and C14/C14 genotypes as well as in the estimated allele frequencies were found. No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD.


Assuntos
Doença de Alzheimer/genética , Demência/genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Estudos Retrospectivos , Estatísticas não Paramétricas , Sequências de Repetição em Tandem/genética
14.
Dement Geriatr Cogn Disord ; 25(3): 287-92, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18303265

RESUMO

BACKGROUND: The glutamatergic neurotransmitter systems play a crucial role in memory formation and information processing. Alterations in this system contribute to the manifestation of symptoms in Alzheimer's disease (AD). Glutamate transmits signals via the N-methyl-D-aspartate receptors (NMDARs). AIMS: The potential involvement of polymorphisms in the GRIN2B gene, encoding subunit 2B of the NMDA receptor, in the risk for AD was evaluated. METHODS: We investigated the 3 single-nucleotide polymorphisms (SNPs) rs1019385, rs1806201 and rs890, i.e. the G(-200)-->T transversion in the 5'UTR, the A(2664)-->G transition in exon 13 and the G(5072)-->T transition in the 3'UTR of the GRIN2B gene, in 222 Caucasian AD patients and 170 healthy Caucasian age-matched controls. RESULTS: No differences were found in the overall distribution of the single-nucleotide polymorphism genotypes between AD patients and healthy controls, even when the analysis was adjusted for sex, age and APOE. As expected from genotype frequencies, no differences were found in the distribution of the estimated allele and haplotype frequencies between AD patients and healthy controls. CONCLUSION: In this study no significant association between polymorphisms in the GRIN2B gene and AD was observed. Further investigations of polymorphisms in the gene encoding the NMDA receptor 2B subunit in AD patients with different genetic setting are needed to clarify their role in the pathogenesis of AD.


Assuntos
Doença de Alzheimer/genética , Receptores de N-Metil-D-Aspartato/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Estudos Transversais , Primers do DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença
15.
Nutrients ; 10(5)2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29751506

RESUMO

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na⁺: p < 0.001; K⁺: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r² = 0.0046, p = 0.77), ESS (r² = 0.0052, p = 0.54) and MNA (r² = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65⁻75 years, p = 0.001; 76⁻85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.


Assuntos
Disfunção Cognitiva/epidemiologia , Desidratação/epidemiologia , Depressão/epidemiologia , Transtornos Neurocognitivos/epidemiologia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Estudos de Casos e Controles , Cloretos/sangue , Disfunção Cognitiva/sangue , Desidratação/sangue , Depressão/sangue , Feminino , Avaliação Geriátrica , Humanos , Masculino , Transtornos Neurocognitivos/sangue , Avaliação Nutricional , Potássio/sangue , Prevalência , Fatores de Risco , Sódio/sangue , Ureia/metabolismo
16.
J Alzheimers Dis ; 62(2): 699-711, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29480171

RESUMO

Alzheimer's disease (AD) and vascular dementia (VaD) lead to progressive decline in executive function. We estimated the prevalence of executive dysfunction in AD and VaD patients, investigating cognitive, functional, and clinical correlates and also using a multidimensional approach based on a standardized comprehensive geriatric assessment (CGA). We included 215 patients (115 AD patients and 100 VaD patients) consecutively evaluated with a complete cognitive and affective assessment, a CGA, and the Frontal Assessment Battery (FAB) with six subtests investigating conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. The prevalence of dysexecutive syndrome screened with a FAB score <12 points was high in both AD (97 patients) and VaD (77 patients) (84.3% versus 77.0%, p = 0.171). AD patients were significantly younger, with higher grade of cognitive impairment and less severe comorbidity and polypharmacy than VaD patients. AD patients showed a significantly higher impairment in FAB total score and five FAB subtests (conceptualization, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy) than VaD patients. These findings were largely confirmed in a sub-analysis conducted subdividing the sample in mild and moderate-to-severe demented patients and suggesting that in moderate-to-severe AD there was higher impairment in FAB total score and four FAB subtests (conceptualization, sensitivity to interference, inhibitory control, and environmental autonomy). Executive dysfunction could be greater in AD patients with moderate-to-severe dementia compared to VaD patients, although our groups were also not matched for age, comorbidity or polypharmacy, which could also exert an effect.


Assuntos
Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Demência Vascular/psicologia , Função Executiva , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Comorbidade , Demência Vascular/complicações , Feminino , Lobo Frontal/patologia , Humanos , Modelos Logísticos , Masculino , Polimedicação , Índice de Gravidade de Doença
17.
Curr Alzheimer Res ; 15(4): 381-385, 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29125073

RESUMO

BACKGROUND: Although it is known that Alzheimer's disease (AD) is associated with the progressive accumulation of amyloid ß-peptide (Aß) in the human brain, its pathogenic role has to be completely clarified. Aß moves from the bloodbrain barrier to the plasma and an increased Aß production in brain could be associated with higher Aß concentrations in blood. A recent study has evaluated Aß40 and Aß42 levels in human red blood cells (RBCs) with evidence of agedependent higher Aß concentration in RBCs. OBJECTIVE: The aim of the study was to investigate if erythrocyte associated Aß (iAß) levels could be different in subjects affected by dementia in comparison with controls and according to the patient's cognitive impairment or different dementia subtypes. METHOD: To answer these questions we assessed iAß40 and iAß42 levels in 116 patients: 32 healthy controls, 39 with diagnosis of vascular dementia (VaD), 14 mild cognitive impairment (MCI) and 31 AD. RESULTS: In this population we found significant differences in iAß42 between controls and cognitive impaired patients. Moreover, iAß42 significantly differed between dementia vs MCI. AD also showed different iAß42 levels as compared to VaD. Conversely, no differences were found for iAß40. All the analyses were adjusted for potential confounders like age, gender and Hb concentration. A direct correlation between increasing iAß42 concentration and the progression of the cognitive decline using the MMSE score as continuous variable was also found. CONCLUSION: Our findings support the evidence that iAß42 could be an instrument to early recognize dementia and predict cognitive impairment.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Demência Vascular/sangue , Demência Vascular/diagnóstico , Eritrócitos/metabolismo , Fragmentos de Peptídeos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Correlação de Dados , Demência Vascular/complicações , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada
19.
J Alzheimers Dis ; 51(2): 427-37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890768

RESUMO

In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p <  0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/psicologia , Delusões/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/mortalidade , Delusões/diagnóstico , Delusões/mortalidade , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Prognóstico , Risco , Índice de Gravidade de Doença , Fatores de Tempo
20.
Am J Alzheimers Dis Other Demen ; 20(3): 167-70, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16003932

RESUMO

The prevalence of Alzheimer's disease (AD) and AD-related dementias (ADRD) in acute ward-hospitalized elderly patients is not well known, owing principally to misclassification and undercoding of AD and ADRD on hospital discharge abstract forms (DAFs). The aims of this study were to evaluate the prevalence of AD and ADRD, as evaluated by the DAF in elderly patients hospitalized in acute wards, and to compare clinical severity, length of stay, comorbidity, and number of diagnostic procedures in patients with AD versus ADRD to explain the different reimbursement costs of DRG12 (AD) versus DRG429 (ADRD). From the inpatient DAF database of the Casa Sollievo della Sofferenza Hospital, the DAFs of patients aged 65 years or over discharged from January 1, 2001, to March 31, 2003, with principal or secondary diagnoses of AD (ICD9-CM code 331) or ADRD (ICD9-CM codes from 290.0 to 290.43) were extracted and grouped by APR-grouper version 12. Age, gender, length of stay, principal and secondary diagnoses and procedures, and APR-DRG severity index (SI) and mortality risk (MR) were evaluated in these patients. Senile dementia was reported in 294 patients (0.58 percent, N = 50,253). In 123 patients (41.8 percent) dementia was the principal diagnosis, whereas in 171 patients (58.2 percent) dementia was reported on the DAF as a secondary diagnosis. Of the 123 patients with a principal diagnosis of dementia, 35 patients were included in the DRG-12 (AD) and 88 patients were included in the DRG-429 (ADRD). No differences were found in mean age, length of stay, comorbidity, or number of diagnostic procedures, as well as in the APR-DRG SI and APR-DRG MR between AD and ADRD patients. Conversely, reimbursement amounts were established as Euro4,033 for DRG-12 (AD) and Euro2,952 for DRG-429 (ADRD). AD and ADRD are undercoded in elderly hospitalized patients. The limits of the ICD9-CM classification system and the influence of reimbursement amounts may influence the coding reports by physicians.


Assuntos
Doença de Alzheimer/classificação , Doença de Alzheimer/diagnóstico , Demência/classificação , Demência/diagnóstico , Processamento Eletrônico de Dados/estatística & dados numéricos , Idoso , Doença de Alzheimer/epidemiologia , Área Programática de Saúde , Demência/epidemiologia , Feminino , Hospitalização , Humanos , Classificação Internacional de Doenças , Itália/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Prevalência , Índice de Gravidade de Doença
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