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OBJECTIVES: To investigate whether rhythmic/periodic EEG patterns (RPP) appearing after propofol discontinuation are more likely to be related to the elimination phase of propofol, or are an expression of severe brain damage. METHODS: In a retrospective cohort of comatose postanoxic patients, EEG was assessed one hour before (baseline) and on hour after discontinuation of propofol. Presence and duration of RPP were related to (changes in) EEG background pattern and duration of sedation. RESULTS: In eleven (of 36 eligible) patients RPP appeared after propofol discontinuation and disappeared in seven of these patients within one hour. A continuous background pattern at baseline and shorter duration of propofol infusion seemed associated with (earlier) spontaneous disappearance of RPP. In ten patients with RPP at baseline, the EEG did not change, and in one patient it changed into burst-suppression. CONCLUSION: Our findings suggest that RPP after propofol discontinuation could be propofol-related. DISCUSSION: RPP might be related to propofol discontinuation rather than an expression of severe brain damage, especially in case of, and congruent with, a continuous pattern at the time of propofol discontinuation. This opens a new insight in this phenomenon and its transient nature. In clinical practice, we suggest to consider the timing of propofol discontinuation when assessing the EEG signal in postanoxic patients.
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Coma , Eletroencefalografia , Propofol , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Eletroencefalografia/métodos , Estudos Retrospectivos , Masculino , Feminino , Coma/etiologia , Coma/induzido quimicamente , Coma/fisiopatologia , Pessoa de Meia-Idade , Idoso , Adulto , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagemRESUMO
OBJECTIVE: To investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD). METHODS: We classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF ß-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD. RESULTS: Fifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A-T-N-), 27% (n = 186) had non-AD pathologic change (A-T-N+, A-T+N-, A-T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T-N-, A+T-N+, A+T+N-, A+T+N+). ATN profiles were unevenly distributed, with A-T+N+, A+T-N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A-T-N-, participants in A+ profiles had a higher risk of dementia with a dose-response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition. CONCLUSIONS: Among individuals presenting with SCD at a memory clinic, those with a biomarker profile A-T+N+, A+T-N-, A+T+N-, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A-T-N- individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.
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Doença de Alzheimer , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/classificação , Progressão da Doença , Idoso , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/patologia , Proteínas tau/líquido cefalorraquidianoRESUMO
Plasma biomarkers are promising prognostic tools in individuals with subjective cognitive decline (SCD). We aimed to investigate the relationships of baseline plasma amyloid beta (Aß)42/Aß40 and total Tau (tTau) with rate of cognitive decline, in comparison to relationships of baseline cerebrospinal fluid (CSF) Aß42, tTau, and phosphorylated tau181 (pTau181) with rate of cognitive decline. We included 241 subjects with SCD (age = 61 ± 9, 40% female, Mini-Mental State Examination = 28 ± 2) with follow-up (average: 2 ± 2 years, median visits: 3 [range: 1-11]) for re-evaluation of neuropsychological test performance (attention, memory, language, and executive functioning domains). Using age, gender and education-adjusted linear mixed models, we found that lower plasma Aß42/Aß40 was associated with steeper rate of decline on tests for attention, memory, and executive functioning, but not language. Lower CSF Aß42 was associated with steeper decline on tests covering all domains. Associations for plasma amyloid and cognitive decline mirror those of CSF amyloid. Plasma tTau was not associated with rate of cognitive decline, whereas CSF tTau and pTau181 were on multiple tests covering all domains.
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Peptídeos beta-Amiloides/sangue , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Envelhecimento Saudável/psicologia , Fragmentos de Peptídeos/sangue , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Função Executiva , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidianoRESUMO
As nutrition is one of the modifiable risk factors for cognitive decline, we studied the relationship between dietary quality and clinical characteristics in cognitively normal individuals with subjective cognitive decline (SCD). We included 165 SCD subjects (age: 64 ± 8 years; 45% female) from the SCIENCe project, a prospective memory clinic based cohort study on SCD. The Dutch Healthy Diet Food Frequency Questionnaire (DHD-FFQ) was used to assess adherence to Dutch guidelines on vegetable, fruit, fibers, fish, saturated fat, trans fatty acids, salt and alcohol intake (item score 0-10, higher score indicating better adherence). We measured global cognition (Mini Mental State Examination), cognitive complaints (Cognitive Change Index self-report; CCI) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D). Using principal component analysis, we identified dietary components and investigated their relation to clinical characteristics using linear regression models adjusted for age, sex and education. We identified three dietary patterns: (i) "low-Fat-low-Salt", (ii) "high-Veggy", and (iii) "low-Alcohol-low-Fish". Individuals with lower adherence on "low-Fat-low-Salt" had more depressive symptoms (ß -0.18 (-2.27--0.16)). Higher adherence to "high-Veggy" was associated with higher MMSE scores (ß 0.30 (0.21-0.64)). No associations were found with the low-Alcohol-low-Fish component. We showed that in SCD subjects, dietary quality was related to clinically relevant outcomes. These findings could be useful to identify individuals that might benefit most from nutritional prevention strategies to optimize brain health.
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Cognição , Disfunção Cognitiva/prevenção & controle , Autoavaliação Diagnóstica , Dieta/classificação , Comportamento Alimentar , Memória , Idoso , Encéfalo , Disfunção Cognitiva/complicações , Estudos Transversais , Demência/prevenção & controle , Depressão/complicações , Depressão/prevenção & controle , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Análise de Componente Principal , Estudos Prospectivos , VerdurasRESUMO
Self-perceived word-finding difficulties are common in aging individuals as well as in Alzheimer's Disease (AD). Language and speech deficits are difficult to objectify with neuropsychological assessments. We therefore aimed to investigate whether amyloid, an early AD pathological hallmark, is associated with speech-derived semantic complexity. We included 63 individuals with subjective cognitive decline (age 64⯱â¯8, MMSE 29⯱â¯1), with amyloid status (positron emission tomography [PET] scans nâ¯=â¯59, or Aß1-42 cerebrospinal fluid [CSF] nâ¯=â¯4). Spontaneous speech was recorded using three open-ended tasks (description of cookie theft picture, abstract painting and a regular Sunday), transcribed verbatim and subsequently, linguistic parameters were extracted using T-scan computational software, including specific words (content words, frequent, concrete and abstract nouns, and fillers), lexical complexity (lemma frequency, Type-Token-Ratio) and syntactic complexity (Developmental Level scale). Nineteen individuals (30%) had high levels of amyloid burden, and there were no differences between groups on conventional neuropsychological tests. Using multinomial regression with linguistic parameters (in tertiles), we found that high amyloid burden is associated with fewer concrete nouns (ORmiddle (95%CI): 7.6 (1.4-41.2), ORlowest: 6.7 (1.2-37.1)) and content words (ORlowest: 6.3 (1.0-38.1). In addition, we found an interaction for education between high amyloid burden and more abstract nouns. In conclusion, high amyloid burden was modestly associated with fewer specific words, but not with syntactic complexity, lexical complexity or conventional neuropsychological tests, suggesting that subtle spontaneous speech deficits might occur in preclinical AD.
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Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Fala/fisiologia , Idoso , Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Diagnóstico Precoce , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia Computadorizada de Emissão de Fóton Único , VocabulárioRESUMO
INTRODUCTION: Within-person trajectories of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) are not well defined. METHODS: We included 467 subjects from the BIOMARKAPD study with at least two serial CSF samples. Diagnoses were subjective cognitive decline (n = 75), mild cognitive impairment (n = 128), and AD dementia (n = 110), and a group of cognitively unimpaired subjects (n = 154) were also included. We measured baseline and follow-up CSF levels of total tau (t-tau), phosphorylated tau (p-tau), YKL-40, and neurofilament light (NfL). Median CSF sampling interval was 2.1 years. RESULTS: CSF levels of t-tau, p-tau, NfL, and YKL-40 were 2% higher per each year of baseline age in controls (P <.001). In AD, t-tau levels were 1% lower (P <.001) and p-tau levels did not change per each year of baseline age. Longitudinally, only NfL (P <.001) and YKL-40 (P <.02) increased during the study period. DISCUSSION: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and p-tau.
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Doença de Alzheimer , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Apolipoproteínas E/genética , Proteína 1 Semelhante à Quitinase-3 , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Fragmentos de Peptídeos , FosforilaçãoRESUMO
BACKGROUND: Biomarkers such as cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) have predictive value for progression to dementia in patients with mild cognitive impairment (MCI). The pre-dementia stage takes far longer, and the interpretation of biomarker findings is particular relevant for individuals who present at a memory clinic, but are deemed cognitively normal. The objective of the current study is to construct biomarker-based prognostic models for personalized risk of clinical progression in cognitively normal individuals presenting at a memory clinic. METHODS: We included 481 individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort. Prognostic models were developed by Cox regression with patient characteristics, MRI, and/or CSF biomarkers to predict clinical progression to MCI or dementia. We estimated 5- and 3-year individualized risks based on patient-specific values. External validation was performed on Alzheimer's Disease Neuroimaging Initiative (ADNI) and an European dataset. RESULTS: Based on demographics only (Harrell's C = 0.70), 5- and 3-year progression risks varied from 6% [3-11] and 4% [2-8] (age 55, MMSE 30) to 38% [29-49] and 28% [21-37] (age 70, MMSE 27). Normal CSF biomarkers strongly decreased progression probabilities (Harrell's C = 0.82). By contrast, abnormal CSF markedly increased risk (5 years, 96% [56-100]; 3 years, 89% [44-99]). The CSF model could reclassify 58% of the individuals with an "intermediate" risk (35-65%) based on the demographic model. MRI measures were not retained in the models. CONCLUSION: The current study takes the first steps in a personalized approach for cognitively normal individuals by providing biomarker-based prognostic models.
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Disfunção Cognitiva/diagnóstico , Progressão da Doença , Idoso , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Demência/líquido cefalorraquidiano , Demência/diagnóstico , Demência/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Fatores de RiscoRESUMO
We examined the relationships between amyloid-ß PET and concurrent and longitudinal cognitive performance in 107 cognitively normal individuals with subjective cognitive decline (age: 64 ± 8 years, 44% female, Mini-Mental State Examination score 29 ± 1). All underwent 90-minute dynamic [18F]florbetapir PET scanning and longitudinal neuropsychological tests with a mean follow-up of 3.4 ± 3.0 years. Receptor parametric mapping was used to calculate [18F]florbetapir binding potential (BPND), and we performed linear mixed models to assess the relationships between global [18F]florbetapir BPND and neuropsychological performance. Higher [18F]florbetapir BPND was related to lower concurrent Mini-Mental State Examination (ß ± SE: -1.69 ± 0.63 p < 0.01) and to steeper rate of decline on tasks capturing memory (Rey Auditory Verbal Learning Task immediate [ß ± SE -1.81 ± 0.81, p < 0.05] and delayed recall [ß ± SE -1.19 ± 0.34, p < 0.01]), attention/executive functions (Stroop II [color] [ß ± SE -0.02 ± 0.01, p < 0.05], Stroop III [word-color] [ß ± SE -0.03 ± 0.02, p < 0.05]), and language (category fluency [ß ± SE -0.04 ± 0.01, p < 0.01]). These findings suggest that higher amyloid-ß load in cognitively normal individuals with subjective cognitive decline from a memory clinic is associated with lower concurrent global cognition and with faster rate of decline in a variety of cognitive domains.
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Peptídeos beta-Amiloides/metabolismo , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Idoso , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de PósitronsRESUMO
Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aß) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aß42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aß42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48% of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12%). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aß42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aß-independent pathways as part of the cascade leading to Alzheimer pathology.
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Apolipoproteínas E/líquido cefalorraquidiano , Apolipoproteínas E/genética , Encéfalo/metabolismo , Clusterina/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Genótipo , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína A-I/líquido cefalorraquidiano , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidianoRESUMO
Objective: Subjective cognitive decline (SCD) is associated with an increased risk of Alzheimer's Disease (AD). Early disease processes, such as amyloid-ß aggregation measured with quantitative PET, may help to explain the phenotype of SCD. The aim of this study was to investigate whether quantitative amyloid-ß load is associated with both self- and informant-reported cognitive complaints and memory deficit awareness in individuals with SCD. Methods: We included 106 SCD patients (mean ± SD age: 64 ± 8, 45%F) with 90 min dynamic [18F]florbetapir PET scans. We used the following questionnaires to assess SCD severity: cognitive change index (CCI, self and informant reports; 2 × 20 items), subjective cognitive functioning (SCF, four items), and five questions "Do you have complaints?" (yes/no) for memory, attention, organization and language), and "Does this worry you? (yes/no)." The Rivermead Behavioral Memory Test (RBMT)-Stories (immediate and delayed recall) was used to assess objective episodic memory. To investigate the level of self-awareness, we calculated a memory deficit awareness index (Z-transformed (inverted self-reported CCI minus episodic memory); higher index, heightened self-awareness) and a self-proxy index (Z-transformed self- minus informant-reported CCI). Mean cortical [18F]florbetapir binding potential (BPND) was derived from the PET data. Logistic and linear regression analyses, adjusted for age, sex, education, and depressive symptoms, were used to investigate associations between BPND and measures of SCD. Results: Higher mean cortical [18F]florbetapir BPND was associated with SCD-related worries (odds ratio = 1.76 [95%CI = 1.07 ± 2.90]), but not with other SCD questionnaires (informant and self-report CCI or SCF, total scores or individual items, all p > 0.05). In addition, higher mean cortical [18F]florbetapir BPND was associated with a higher memory deficit awareness index (Beta = 0.55), with an interaction between BPND and education (p = 0.002). There were no associations between [18F]florbetapir BPND and self-proxy index (Beta = 0.11). Conclusion: Amyloid-ß deposition was associated with SCD-related worries and heightened memory deficit awareness (i.e., hypernosognosia), but not with severity of cognitive complaints. Our findings indicate that worries about self-perceived decline may reflect an early symptom of amyloid-ß related pathology rather than subjective cognitive functioning.
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INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). METHODS: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aß)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. RESULTS: The prevalence of abnormal Aß42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aß42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aß42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. CONCLUSIONS: While heterogeneous frequency of abnormal Aß42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD.
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Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/epidemiologia , Autoavaliação Diagnóstica , Ambulatório Hospitalar/tendências , Idoso , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/psicologia , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Prevalência , Proteínas tau/líquido cefalorraquidianoRESUMO
INTRODUCTION: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. METHODS: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. RESULTS: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini-Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E ε4 (1.8 [1.3-2.5]) increased the risk of dementia. DISCUSSION: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts.
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Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Estudos de Coortes , Demência/psicologia , Autoavaliação Diagnóstica , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , AutoimagemRESUMO
BACKGROUND: We aimed to describe the Subjective Cognitive Impairment Cohort (SCIENCe) study design, to cross-sectionally describe participant characteristics, and to evaluate the SCD-plus criteria. METHODS: The SCIENCe is a prospective cohort study of subjective cognitive decline (SCD) patients. Participants undergo extensive assessment, including cerebrospinal fluid collection and optional amyloid positron emission tomography scan, with annual follow-up. The primary outcome measure is clinical progression. RESULTS: Cross-sectional evaluation of the first 151 participants (age 64 ± 8, 44% female, Mini-Mental State Examination 29 ± 2) showed that 28 (25%) had preclinical Alzheimer's disease (AD) (amyloid status available n = 114 (75%)), 58 (38%) had subthreshold psychiatry, and 65 (43%) had neither. More severe subjective complaints were associated with worse objective performance. The SCD-plus criteria age ≥ 60 (OR 7.7 (95% CI 1.7-38.9)) and apolipoprotein E (genotype) e4 (OR 4.8 (95% CI 1.6-15.0)) were associated with preclinical AD. CONCLUSIONS: The SCIENCe study confirms that SCD is a heterogeneous group, with preclinical AD and subthreshold psychiatric features. We found a number of SCD-plus criteria to be associated with preclinical AD. Further inclusion and follow-up will address important questions related to SCD.
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Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico por imagem , Projetos de Pesquisa , Idoso , Amiloide/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Inquéritos e Questionários , Proteínas tau/líquido cefalorraquidianoRESUMO
INTRODUCTION: Individuals with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease and could benefit from a prevention strategy targeting lifestyle factors. Making a program available through the Internet gives a widespread reach at low cost, but suboptimal adherence is a major threat to effectiveness. As a first step in developing an online lifestyle program (OLP), we aimed to identify factors that are barriers and/or facilitators for the use of an OLP in individuals with SCD in three European countries. METHODS: As part of the Euro-SCD project, SCD subjects were recruited at memory clinics in the Netherlands, Germany, and Spain. We combined quantitative and qualitative methods, using a mixed methods approach. We conducted an online 18-item survey on the preferences of SCD patients for an OLP (N = 238). In addition, we held semi-structured interviews (N = 22) to gain in-depth understanding of factors acting as a facilitator and/or barrier for intended use of an OLP. Audio recordings were transcribed verbatim. Content analysis was performed. RESULTS: One hundred seventy-six individuals completed the survey (response rate 74%). Almost all participants regularly use the Internet (97%). Participants reported trustworthiness (93%), user-friendliness (91%), and up-to-date information (88%) as main facilitators, whereas having contact with other users (26%), needing an account (21%), and assignments (16%) were reported as barriers. Barriers differed slightly between countries, but facilitators were largely similar. In-depth interviews revealed that both program characteristics (e.g., trustworthiness, user-friendliness, and personalization) and personal factors (e.g., expectancy to receive negative feedback) are likely to influence the intended use of an OLP. DISCUSSION: Involving users provided in-depth understanding of factors associated with the intended use of an OLP for brain health. Both program characteristics and personal factors are likely to influence the use of an OLP. Based on this input from the end-users, we will develop an OLP for individuals with SCD.
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OBJECTIVES: Grey matter network disruptions in Alzheimer's disease (AD) are associated with worse cognitive impairment cross-sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD). EXPERIMENTAL DESIGN: We included 231 individuals with SCD who had annually repeated neuropsychological assessment (3 ± 1 years; n = 646 neuropsychological investigations) available from the Amsterdam Dementia Cohort (54% male, age: 63 ± 9, MMSE: 28 ± 2). Single-subject grey matter networks were extracted from baseline 3D-T1 MRI scans and we computed basic network (size, degree, connectivity density) and higher-order (path length, clustering, betweenness centrality, normalized path length [lambda] and normalized clustering [gamma]) parameters at whole brain and/or regional levels. We tested associations of network parameters with baseline and annual cognition (memory, attention, executive functioning, language composite scores, and global cognition [all domains with MMSE]) using linear mixed models, adjusted for age, sex, education, scanner and total gray matter volume. PRINCIPAL OBSERVATIONS: Lower network size was associated with steeper decline in language (ß ± SE = 0.12 ± 0.05, p < 0.05FDR). Higher-order network parameters showed no cross-sectional associations. Lower gamma and lambda values were associated with steeper decline in global cognition (gamma: ß ± SE = 0.06 ± 0.02); lambda: ß ± SE = 0.06 ± 0.02), language (gamma: ß ± SE = 0.11 ± 0.04; lambda: ß ± SE = 0.12 ± 0.05; all p < 0.05FDR). Lower path length values in precuneus and fronto-temporo-occipital cortices were associated with a steeper decline in global cognition. CONCLUSIONS: A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment.
Assuntos
Encéfalo/fisiopatologia , Cognição , Disfunção Cognitiva/fisiopatologia , Substância Cinzenta/fisiopatologia , Idioma , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Autoavaliação Diagnóstica , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , PercepçãoRESUMO
INTRODUCTION: Individuals with subjective cognitive decline (SCD) are at increased risk for clinical progression. We studied how combining different diagnostic tests can help to identify individuals who are likely to show clinical progression. METHODS: We included 674 patients with SCD (46% female, 64 ± 9 years, Mini-Mental State Examination 28 ± 2) from three memory clinic cohorts. A multivariate model based on the Disease State Index classifier incorporated the available baseline tests to predict progression to MCI or dementia over time. We developed and internally validated the model in one cohort and externally validated it in the other cohorts. RESULTS: After 2.9 ± 2.0 years, 151(22%) patients showed clinical progression. Overall performance of the classifier when combining cognitive tests, magnetic resonance imagining, and cerebrospinal fluid showed a balanced accuracy of 74.0 ± 5.5, with high negative predictive value (93.3 ± 2.8). DISCUSSION: We found that a combination of diagnostic tests helps to identify individuals at risk of progression. The classifier had particularly good accuracy in identifying patients who remained stable.
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INTRODUCTION: Synaptic membrane formation depends on nutrients that fuel metabolic pathways for the synthesis of constituent phospholipids. Consequently, insufficient availability of such nutrients may restrict membrane formation and contribute to synaptic dysfunction in Alzheimer's disease (AD). We assessed whether blood and cerebrospinal fluid (CSF) concentrations of nutrients related to phospholipid synthesis differ among patients with AD, mild cognitive impairment (MCI), and control subjects. METHODS: Concentrations of uridine, choline, folate, homocysteine, and other related metabolites were analyzed in paired blood and CSF samples from subjects selected from the Amsterdam Dementia Cohort with AD (n = 150; age, 66 ± 7 years; 37% female), MCI (n = 148; age, 66 ± 8 years; 37% female), and control subjects (n = 148; age, 59 ± 8 years; 38% female). RESULTS: Age- and gender-adjusted analysis of variance revealed different concentrations of circulating uridine, choline, and folate and CSF uridine, folate, and homocysteine (all P < .05) among the three diagnostic groups. Post hoc pairwise comparison showed that subjects with AD had lower CSF uridine, plasma choline and higher CSF homocysteine concentrations, whereas subjects with MCI had lower plasma and CSF uridine, serum and CSF folate, and higher CSF homocysteine concentrations compared with control subjects (all P < .05), with differences ranging from -11 to +22%. DISCUSSION: AD and MCI patients have lower levels of nutrients involved in phospholipid synthesis. The current observations warrant exploration of the application of nutritional strategies in the early stages of AD.
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A lumbar puncture is performed to obtain cerebral spinal fluid. It is implemented in the clinic on a routine basis to aid the diagnosis of neurologic diseases, such as dementia. This video will show the lumbar puncture procedure as routinely performed in the VUmc Alzheimer Center.
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BACKGROUND: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-ß aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer's disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. OBJECTIVE: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. METHODS: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; nâ=â206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; nâ=â223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOEÉ4 carriership. RESULTS: 117 patients (27%) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30% increased risk of clinical progression (hazard ratio (HR) (95% CI) â=â1.3(1.0-1.6)). The effect appeared to be attributable to the APOEÉ4 carriers with SCD (HR 3.3(1.0-10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEÉ4 carriers with SCD (HR 5.0(1.3-18.9)). CONCLUSION: Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOEÉ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.