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1.
J Intern Med ; 275(4): 428-36, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24410954

RESUMO

OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Barreira Hematoencefálica , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Administração Oral , Adulto , Doença de Alzheimer/tratamento farmacológico , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Progressão da Doença , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacocinética , Método Duplo-Cego , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/líquido cefalorraquidiano , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/líquido cefalorraquidiano , Seguimentos , Humanos , Fosforilação , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano
2.
Dement Geriatr Cogn Disord ; 37(3-4): 196-206, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24157938

RESUMO

OBJECTIVE: Cerebrospinal fluid (CSF) amyloid ß42 (Aß42), total tau (t-tau) and phosphorylated tau (p-tau) are useful as predictors of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. However, results are contradictory as to whether these biomarkers reflect the future rate of clinical decline. METHODS: This is a retrospective study on 196 patients with AD [mild/moderate AD (n = 72) or AD-MCI (n = 124) at baseline] with a follow-up period of 2-9 years' duration (median 6 years). Lumbar punctures were performed at baseline as a part of the diagnostic procedure. RESULTS: We found an increased risk of rapid cognitive decline defined as a drop in the Mini-Mental State Examination score of ≥ 4 points/year in patients with CSF t-tau concentrations above the median (OR 3.31, 95% CI 1.53-7.16) and CSF p-tau above the median (OR 2.53, 95% CI 1.21-5.26). Patients with CSF t-tau in the highest quartile had a higher risk of dying in severe dementia (HR 4.67, 95% CI 1.16-18.82). CONCLUSIONS: In this large AD cohort, we found an association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease, measured as a rapid cognitive decline and a higher risk of dying in severe dementia.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/mortalidade , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Fosforilação , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
3.
Dement Geriatr Cogn Dis Extra ; 3(1): 472-81, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24516415

RESUMO

OBJECTIVES: There is an overlap regarding Pittsburgh compound B (PIB) retention in patients clinically diagnosed as Alzheimer's disease (AD) and non-AD dementia. The aim of the present study was to investigate whether there are any differences between PIB-positive and PIB-negative patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). METHODS: Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting. RESULTS: The PIB-positive patients (7 out of 18) had slower psychomotor speed and more impaired visual episodic memory than the PIB-negative patients; otherwise performance did not differ between the groups. The initial clinical diagnoses were changed in one third of the patients (6 out of 18) during follow-up. CONCLUSIONS: The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need for amyloid biomarkers and a readiness to re-evaluate the initial diagnosis.

4.
Dement Geriatr Cogn Disord ; 29(3): 204-12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20332638

RESUMO

BACKGROUND: The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring beta-amyloid (Abeta) load. Associations between PET PIB and cerebrospinal fluid (CSF) Abeta1-42 and apolipoprotein E epsilon4 (APOE epsilon4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer's disease (AD) are less investigated. METHOD: PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD. RESULTS: PIB retention was constant over 1 year, inversely related to low CSF Abeta1-42 (p = 0.01) and correlated positively to the numbers of the APOE epsilon4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = -0.59, p = 0.07), and plasma cystatin C (r = -0.56, p = 0.09). CONCLUSION: PIB retention is strongly related to CSF Abeta1-42, and to the numbers of the APOE epsilon4 allele.


Assuntos
Doença de Alzheimer/metabolismo , Compostos de Anilina/análise , Tiazóis/análise , Idoso , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/urina , Compostos de Anilina/metabolismo , Apolipoproteínas E/genética , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/urina , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Interpretação Estatística de Dados , Educação , Ensaio de Imunoadsorção Enzimática , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Psicometria , Compostos Radiofarmacêuticos , Fatores de Risco , Tiazóis/metabolismo
5.
Acta Neurol Scand ; 122(4): 270-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20047570

RESUMO

OBJECTIVES: Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) has become a standard clinical trials outcome for cognition, but has been recognized as deficient in areas including coverage of cognitive domains, sensitivity and standardization. Computerized test batteries may address some of these issues. The cognitive drug research computerized assessment (CDR) system is validated in Alzheimer's disease (AD). This study was designed to further evaluate validity in relation to ADAS-Cog, mini mental state examination (MMSE) and cerebrospinal fluid (CSF) biomarkers and psychometric properties, in a population of Alzheimer's patients on stable anticholinesterase treatment. MATERIALS AND METHODS: Patients completed cognition assessments, CSF and blood sampling at baseline and 6 months later. Data for 65 patients were evaluated. RESULTS: The CDR system demonstrated good psychometric properties in this population. Measures of psychomotor speed showed possible sensitivity to decline over 6 months. CONCLUSIONS: There are a number of methodological problems with current cognition assessment methodology for clinical trials. Computerized measures and in particular millisecond reaction time measures, may address many of these issues.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Inibidores da Colinesterase/uso terapêutico , Cognição , Testes Neuropsicológicos , Atenção , Feminino , Humanos , Masculino , Memória , Psicometria , Desempenho Psicomotor , Reprodutibilidade dos Testes
6.
Acta Neurol Scand ; 121(3): 186-93, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19785641

RESUMO

OBJECTIVES: To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer's disease (AD). MATERIALS AND METHODS: Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and MMSE were administered concurrently. RESULTS: Correlations (rho) between age and AQT processing speed were non-significant, but were significant for ADAS-Cog and Mini Mental State Examination (MMSE). AQT and ADAS-Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman's rho) were moderate-to-high for all tests. Means for subgroups did not differ as a function of medication type. CONCLUSIONS: AQT processing speed, ADAS-Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Inibidores da Colinesterase/uso terapêutico , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Análise de Variância , Feminino , Seguimentos , Humanos , Masculino , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
7.
Neurology ; 71(14): 1072-9, 2008 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-18824671

RESUMO

BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.


Assuntos
Envelhecimento/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Cistatinas/sangue , Citoproteção/fisiologia , Idoso , Doença de Alzheimer/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Causalidade , Estudos de Coortes , Cistatina C , Cistatinas/análise , Regulação para Baixo/fisiologia , Humanos , Hiperlipidemias/epidemiologia , Nefropatias/epidemiologia , Estudos Longitudinais , Masculino , Obesidade/epidemiologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/epidemiologia , Suécia/epidemiologia
8.
Dement Geriatr Cogn Disord ; 24(4): 247-52, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17700020

RESUMO

BACKGROUND: Memantine is a moderate affinity N-methyl-D-aspartate receptor antagonist approved for treatment of Alzheimer's disease (AD). In AD, tau is abnormally hyperphosphorylated. However, no significant changes of phosphorylated tau levels in CSF are found at follow-up in studies with AD patients. It has been shown in vitro that memantine reverse induced abnormal hyperphosphorylation of tau in hippocampal neurons of rats. METHODS: Eleven AD patients were examined with cognitive tests and interviews of relatives. CSF analyses were performed before starting treatment with memantine as well as after 1 year. RESULTS: A statistically significant reduction of CSF phosphorylated tau at the 1-year follow-up was seen, from median 126 (interquartile range 107-153) to 108 (88-133) ng/l (p = 0.018). No statistically significant differences of total tau or Abeta42 were found. CONCLUSION: The results may reflect effects of memantine on a key pathological feature in AD in line with previous in vitro findings.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Memantina/uso terapêutico , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Fatores de Tempo
9.
Eur J Clin Nutr ; 59(8): 947-54, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15942639

RESUMO

OBJECTIVE: We investigated the nutritional, cognitive and functional status in residents of two service-flat (SF) complexes and the effects of a nutrition education programme for care staff. DESIGN: Controlled nonrandomised study. SETTING: Two SF complexes, that is community-assisted accommodation. SUBJECTS: Of 115 eligible SF residents, 80 subjects participated (age 83+/-7 y, 70% women). INTERVENTION: The nutritional status was assessed using body mass index (BMI, kg/m(2)), subjective global assessment (SGA), serum concentrations of albumin, insulin-like growth factor-I (IGF-I) and vitamin B(12). Cognitive and functional status were evaluated using the Mini Mental State Examination (MMSE, 0-30 points, <24 points indicates impaired cognition) and the Katz activities of daily living (ADL) index, respectively. Two assessments were made with a 5-month interval. At the start, a 12-h education programme was given to the staff at one of the SF complexes. RESULTS: At baseline, the means of BMI and the biochemical nutritional indices were normal, whereas one-third had BMI <22 kg/m(2) and one-fourth had lost > or =10% of previous weight. According to SGA, 30% demonstrated possible or serious malnutrition. The median MMSE was 23 points (19.5-26.5, 25-75th percentile). Nearly 70% were ADL-independent. At the 5-month follow-up there were no differences in the nutritional and cognitive status of the residents. The nutritional knowledge of the staff improved slightly (P<0.05) at both SF complexes (NS between groups). CONCLUSIONS: Around one-third of SF residents appeared to be at nutritional risk. Five months after a 12-h staff nutrition education programme, no objective changes were seen in the nutritional status of the SF residents.


Assuntos
Envelhecimento/fisiologia , Pessoal de Saúde/educação , Distúrbios Nutricionais/prevenção & controle , Ciências da Nutrição/educação , Estado Nutricional , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Cognição , Feminino , Avaliação Geriátrica , Conhecimentos, Atitudes e Prática em Saúde , Habitação para Idosos , Humanos , Masculino , Desenvolvimento de Pessoal
10.
J Intern Med ; 256(3): 240-6, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15324367

RESUMO

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.


Assuntos
Transtornos Cognitivos/diagnóstico , Idoso , Biomarcadores/líquido cefalorraquidiano , Pesquisa Biomédica , Transtornos Cognitivos/genética , Transtornos Cognitivos/terapia , Diagnóstico por Imagem/métodos , Humanos , Testes Neuropsicológicos
11.
J Neural Transm Suppl ; (62): 117-25, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12456057

RESUMO

The characterisation of the borderline syndrome between normal cognitive function and Alzheimer's disease (AD), often mentioned as Mild Cognitive Impairment (MCI) has been a goal for recent research. However, a variety of definitions of MCI-like syndromes and the uncertainty about the final diagnosis have hampered progress. To overcome these problems, the present study will describe cognitive function in two healthy mutation carriers and two matched non-carriers of the Swedish double mutation family, during the time period when carriers convert to a symptomatic stage, i.e., true preclinical AD, and finally into the stage when a clinical diagnosis of AD is first possible. The findings question the generality of common MCI concepts and the commonly held beliefs about cognitive features in late preclinical stage of AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Progressão da Doença , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Suécia
12.
Eur J Clin Nutr ; 56(3): 221-7, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11960297

RESUMO

OBJECTIVES: We studied the nutritional status and the effects of nutritional intervention on body weight, cognition and activities of daily life (ADL)-function in demented individuals. DESIGN: Controlled non-randomised study. SETTING: Group-living for demented elderly (GLD), ie community assisted housing. SUBJECTS AND INTERVENTIONS: Twenty-two residents living in one of two units (GLD-I), received oral liquid supplements (1720 kJ/410 kcal/day) and the personnel of the GLD-I were given nutritional education. Fourteen residents in the other unit (GLD-C) served as controls. After 6 months 21 (83 (4) y, 81% women) and 12 (85 (4) y, 100% women) of the participants, respectively, were re-examined according to body mass index (BMI, kg/m2), cognitive function (Mini Mental State Examination (MMSE, 0-30 p) and Clinical Dementia Rating Scale (CDR) and the Katz' ADL index. RESULTS: Body mass index (BMI) < or =20 was found in 19% of the participants and 44% had BMI< or =23. BMI correlated with MMSE (r=0.43, P<0.01). The weight of the residents in the intervention group increased by 3.4 (3) kg (P=0.001) at follow-up, whereas the weight remained unchanged in the control group. The cognitive function was low at the start in both groups, ie MMSE approximately 9 and no apparent positive effect of the nutritional intervention was seen. In addition, the ADL functions appeared to deteriorate in both groups. CONCLUSIONS: Being underweight was common among demented elderly in group-living and was related to low cognitive capacity. Five months of oral supplementation, along with education of personnel, was followed by a weight gain. In this study the nutritional treatment did not affect the rate of decline in cognitive function or Katz' ADL index. SPONSORSHIP: Supported by grants from the Swedish National Board of Health and Social Welfare. Semper Foods AB provided the liquid supplements.


Assuntos
Demência/dietoterapia , Instituição de Longa Permanência para Idosos , Casas de Saúde , Avaliação Nutricional , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Bebidas , Índice de Massa Corporal , Cognição/fisiologia , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Masculino , Suécia
13.
J Neural Transm (Vienna) ; 108(4): 451-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11475012

RESUMO

Today, cognitive impairment can be successfully treated with acetylcholine esterase inhibitors (AChE-I) in many, but not all, patients with Alzheimer's disease (AD). To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC scores (efficacy parameters) after 6 and 12 months of tacrine (an AChE-I) treatment were investigated in 145 AD patients. Of these, 84 were ApoE epsilon4-positive (ApoE4) and 61 were ApoE epsilon4-negative (ApoE2-3). No differences were found after 6 months of treatment, but after 12 months the CIBIC scores revealed that the ApoE4 patients had declined more than the ApoE2-3 patients (p < 0.05). No differences were found for the last 6 months of treatment. The results primarily suggest a faster rate of decline in the ApoE4 AD compared to the ApoE2-3, but may also reflect that ApoE epsilon4 genotype inheritance is a negative predictor of treatment effect of tacrine in AD patients.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Nootrópicos/uso terapêutico , Tacrina/uso terapêutico , Idoso , Alelos , Apolipoproteína E4 , Inibidores da Colinesterase/farmacologia , Progressão da Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria
14.
Neurology ; 56(9): 1188-94, 2001 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-11342684

RESUMO

OBJECTIVE: To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. METHODS: A population-based longitudinal study in Sweden, the Kungsholmen PROJECT: A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. RESULTS: When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. CONCLUSIONS: This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.


Assuntos
Doença de Alzheimer/sangue , Ácido Fólico/sangue , Vitamina B 12/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica
15.
Dement Geriatr Cogn Disord ; 12(2): 127-32, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11173885

RESUMO

Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer's disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45-80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.


Assuntos
Envelhecimento/fisiologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Apolipoproteínas E/metabolismo , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton Único
16.
Am J Epidemiol ; 153(3): 225-31, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11157409

RESUMO

The authors examined the impact of the apolipoprotein E (APOE)(*)epsilon4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged >/=75 years was followed for an average of 3 years (1990-1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with (*)epsilon3/(*)epsilon3, the APOE(*)epsilon4 allele increased the risk of developing dementia (relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1) and Alzheimer's disease (RR = 1.7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among (*)epsilon4 carriers. For those not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (95% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE(*)epsilon4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.


Assuntos
Doença de Alzheimer/genética , Anti-Hipertensivos/uso terapêutico , Apolipoproteínas E/genética , Demência Vascular/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Apolipoproteína E3 , Apolipoproteína E4 , Demência Vascular/diagnóstico , Demência Vascular/epidemiologia , Diagnóstico Diferencial , Feminino , Genótipo , Humanos , Incidência , Estudos Longitudinais , Masculino , Estudos Prospectivos , Suécia/epidemiologia
17.
Am J Ind Med ; 38(3): 290-4, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10940966

RESUMO

BACKGROUND: The Kungsholmen project is a longitudinal study of ageing and dementia conducted in Stockholm in 1987. In a 1994-96 follow-up, 804 subjects had their blood samples analyzed for lead. METHODS: Lead concentration in blood in an elderly population aged 75+ (mean age of 88.4 years) was studied in relation to age, blood pressure (BP), body mass index (BMI), cognitive function measured with Mini-Mental State Examination (MMSE), gender, and smoking. RESULTS: The mean blood lead level (n = 762) was 3.7 microg/dL (0.18 micromol/L) whole blood with a standard deviation of 2.3, (0.11). There was a contribution of gender with men having higher blood lead levels than women (beta = -0.20; P = 0.000001) but not of smoking habits (beta = 0.07; P = 0.08) when these variables were entered into a multiple regression model with lead as the dependent variable (R = 0.22; P < 0.000001). Different multiple regression models were tested with lead as the dependent variable. No relation was found between lead concentrations and age, BMI, systolic BP, diastolic BP, or MMSE. Systolic and diastolic BP were correlated to BMI (R = 0.10; P = 0.01 and R = 0.22; P = 0.000 001, respectively). CONCLUSIONS: In this elderly population from a specified area of Stockholm it is unlikely that lead exposure affects BP or cognition. However, high lead levels in blood may reflect earlier occupational exposure or life style factors.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Chumbo/efeitos adversos , Chumbo/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores Sexuais , Fumar , Suécia , População Urbana
19.
Stroke ; 31(1): 53-60, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10625715

RESUMO

BACKGROUND AND PURPOSE: Both stroke and the apolipoprotein E (APOE) epsilon4 allele increase the risk of dementia. However, the interaction between stroke and APOE on dementia is still unclear. We addressed this topic by using a longitudinal design. METHODS: We followed up a community cohort of 1301 subjects aged >/=75 years, who did not have dementia at baseline. Among them, 92 subjects had a history of stroke (from 3 months to 16 years before baseline interview). After the 3-year follow-up, 224 dementia cases had been diagnosed. During the period of follow-up, 91 subjects had a first occurrence of stroke (incident stroke). The APOE genotype was known for 985 subjects. Cox proportional hazards regression models were constructed to estimate the risk for dementia in terms of relative risks (RRs) for stroke and the APOE epsilon4 allele, with adjustment for age, sex, education, systolic blood pressure, antihypertensive medication use, and heart disease. RESULTS: In the entire study population, RRs for dementia related to history of stroke and incident stroke were 1.7 (95% CI, 1.1 to 2.6) and 2.4 (95% CI, 1.6 to 3.5), respectively, after adjustment for all potential confounders. Subjects with stroke that occurred within 3 years before baseline had RR of 2.4 (95% CI, 1.4 to 4.2), whereas those with stroke occurring >3 years before baseline had RR of dementia of 1.1 (95% CI, 0.6 to 2.3). Among those with APOE information, individuals with only history of stroke (that occurred within 3 years before baseline) had RR of 3.1 (95% CI, 1.4 to 6.6), individuals with only the APOE epsilon4 allele had RR of 1.7 (95% CI, 1.1 to 2.5), and individuals with both factors had RR of 5.3 (95% CI, 2.1 to 13.4). The corresponding figures when incident stroke was examined instead of history of stroke were 2.3 (95% CI, 1.3 to 4.1), 1.7 (95% CI, 1.1 to 2.4), and 4.6 (95% CI, 2.0 to 10.6), respectively. The RR of interaction term for history of stroke and APOE epsilon4 was 1.1 (95% CI, 0.3 to 3.8; P=0.8). The corresponding figure was 1.2 (95% CI, 0.4 to 4.4; P=0.7) for incident stroke and APOE epsilon4. Furthermore, the RRs of dementia without any stroke and dementia with stroke in relation to APOE epsilon4 were 1.6 (95% CI, 1.1 to 2.3) and 1.2 (95% CI, 0.6 to 2.4), respectively. In addition, the APOE epsilon4 allele was not significantly related to the occurrence of stroke (RR=0.8; 95% CI, 0.5 to 1.5). CONCLUSIONS: A relatively fresh stroke is a risk factor for dementia. APOE epsilon4 increases the risk of dementia without stroke but not dementia with stroke. Our data do not support a multiplicative effect of stroke and the APOE epsilon4 allele on the risk of dementia. However, both factors seem to have an additive effect on the risk of dementia. The APOE epsilon4 allele does not increase the risk of stroke in this Swedish elderly population.


Assuntos
Alelos , Apolipoproteínas E/genética , Demência/complicações , Demência/genética , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Idoso , Idoso de 80 Anos ou mais , Demência/epidemiologia , Humanos , Incidência , Acidente Vascular Cerebral/epidemiologia , Suécia/epidemiologia
20.
Biometals ; 13(4): 311-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11247037

RESUMO

Concentration of cadmium in blood in an elderly population with a mean age of 87 years was studied in relation to age, blood pressure, BMI, cognitive function, gender and smoking. This population-based study consisted of 804 subjects both men and women. Clinical examination included medical and social history, physical and neurologic examination, and assessment of cognitive functions with Mini-Mental State Examination (MMSE). Information on prescription and non-prescription drug use was collected. Anti-hypertensive drugs included all medicines potentially used for treating high blood pressure. Blood pressure was measured. Whole blood from 763 subjects was analysed for cadmium by atomic absorption spectrophotometry (GFAAS) with Zeeman background correction and with a graphite furnace using the L'vov platform technique including quality control. Differences in cadmium concentrations were related to non-smokers (3.9 nmol/l), previous smokers (4.4 nmol/l) and current smokers (7.5 nmol/l). There were no relations between cadmium and age, blood pressure or cognitive functions. In conclusion, increased cadmium levels were found in smokers. A possible contribution from previous occupational exposure needs to be further evaluated.


Assuntos
Cádmio/sangue , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Índice de Massa Corporal , Cognição , Feminino , Humanos , Masculino , Fumar/sangue , Suécia , População Urbana
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