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Background/aims: The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Methods: MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E É4 (APOE É4) carrier status. Results: Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses. Conclusion: The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.
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Objective: To evaluate prevalence and factors determining not returning to full-time work 1 year after first-ever mild ischemic stroke. Design: Prospective, observational cohort study with 12-month follow-up. Setting: Stroke units and outpatient clinics at 2 Norwegian hospitals. Participants: We included 84 (N=84) full-time working, cognitively healthy patients aged 70 years or younger who suffered an acute first-ever mild ischemic stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score ≤3 points. Interventions: Not applicable. Main Outcome Measures: Vascular risk factors, sociodemographic factors, stroke localization, and etiology were recorded at inclusion. Cognitive impairment, anxiety, depression, fatigue, and apathy 12 months after stroke were assessed with validated instruments. Logistic regression analyses were performed to find correlates of not returning to full-time employment. Results: Of 78 patients assessed 1 year after stroke, 63 (81%) had returned to work, 47 (60%) to full-time employment status. Modified Rankin scale score >1 (adjusted odds ratio, 12.44 [95% confidence interval, 2.37-65.43], P=.003) at follow-up was significantly associated, and diabetes (adjusted odds ratio, 10.56 [95% confidence interval, 0.98-113.47], P=.052) was borderline significantly associated with not returning to full-time work. Female sex, NIHSS at discharge, anxiety per point on the anxiety scale, depression per point on the depression scale, and fatigue per point on the fatigue scale were significantly associated with not returning to full-time work after 1 year, but these associations were only seen in the unadjusted models. Conclusions: Low functional level that persists 12 months after stroke is related to not returning to full-time work. Patients with diabetes mellitus, female patients, and patients with a higher score on fatigue, anxiety, and depression scales may also be at risk of not returning to full-time work post stroke. Working patients should be followed up with a particular focus on factors determining participation in work and social life.
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Even mild strokes may affect the patients' everyday life by impairing cognitive and emotional functions. Our aim was to study predictors of such impairments one year after first-ever mild stroke. We included cognitively healthy patients ≤ 70 years with acute mild stroke. Vascular risk factors, sociodemographic factors and stroke classifications were recorded. At one-year post-stroke, different domains related to cognitive and emotional function were assessed with validated instruments. Logistic regression analyses were performed to identify predictors of cognitive and emotional outcome. Of 117 patient assessed at follow-up, only 21 patients (18%) scored within the reference range on all cognitive and emotional assessments. Younger age, multiple infarcts, and being outside working life at stroke onset were independent predictors of cognitive impairments (psychomotor speed, attention, executive and visuospatial function, memory). Female gender and a higher National Institutes of Health Stroke Scale (NIHSS) score at discharge were significantly associated with emotional impairments (anxiety, depressive symptoms, fatigue, apathy, emotional lability) after one year, but these associations were only seen in the unadjusted models. In conclusion, patients in working age may profit from a follow-up during the post-stroke period, with extra focus on cognitive and emotional functions.
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Apatia , Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Feminino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Ansiedade , CogniçãoRESUMO
Neurodegenerative dementia may, in rare cases, initially manifest as isolated language impairments in the absence of other cognitive symptoms. These impairments are often somewhat imprecisely referred to as difficulties with 'word finding'. There are several variants of this form of dementia, each caused by different underlying neuropathologies. Occasionally problems with speech rather than language predominate. Patients may have exclusively language or speech-related symptoms for several years, but eventually all will progress to generalised dementia. This clinical review describes primary progressive aphasia: a collective term for forms of dementia that begin with language impairments.
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Afasia Primária Progressiva , Humanos , Afasia Primária Progressiva/diagnóstico , Afasia Primária Progressiva/patologia , IdiomaRESUMO
PURPOSE: The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data. PARTICIPANTS: The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009-2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders. FINDINGS TO DATE: All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources. FUTURE PLANS: The finish date of NorCog was originally in 2029. In 2021, the registry's legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.
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Materiais Biocompatíveis , Demência , Humanos , Idoso , Atividades Cotidianas , Sistema de Registros , Instituições de Assistência Ambulatorial , Cognição , Demência/diagnósticoRESUMO
BACKGROUND: Polygenic hazard scores (PHS) estimate age-dependent genetic risk of late-onset Alzheimer's disease (AD), but there is limited information about the performance of PHS on real-world data where the population of interest differs from the model development population and part of the model genotypes are missing or need to be imputed. OBJECTIVE: The aim of this study was to estimate age-dependent risk of late-onset AD using polygenic predictors in Nordic populations. METHODS: We used Desikan PHS model, based on Cox proportional hazards assumption, to obtain age-dependent hazard scores for AD from individual genotypes in the Norwegian DemGene cohort (nâ=â2,772). We assessed the risk discrimination and calibration of Desikan model and extended it by adding new genotype markers (the Desikan Nordic model). Finally, we evaluated both Desikan and Desikan Nordic models in two independent Danish cohorts: The Copenhagen City Heart Study (CCHS) cohort (nâ=â7,643) and The Copenhagen General Population Study (CGPS) cohort (nâ=â10,886). RESULTS: We showed a robust prediction efficiency of Desikan model in stratifying AD risk groups in Nordic populations, even when some of the model SNPs were missing or imputed. We attempted to improve Desikan PHS model by adding new SNPs to it, but we still achieved similar risk discrimination and calibration with the extended model. CONCLUSION: PHS modeling has the potential to guide the timing of treatment initiation based on individual risk profiles and can help enrich clinical trials with people at high risk to AD in Nordic populations.
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Doença de Alzheimer , Idade de Início , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Genótipo , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Having accurate, up-to-date information on the epidemiology of mild cognitive impairment (MCI) and dementia is imperative. OBJECTIVE: To determine the prevalence of MCI and dementia in Norway using data from a large population-based study. METHODS: All people 70â+âyears of age, nâ=â19,403, in the fourth wave of the Trøndelag Health Study (HUNT4) were invited to participate in the study HUNT4 70â+â. Trained health personnel assessed participants using cognitive tests at a field station, at homes, or at their nursing home. Interviewers also completed a structured carer questionnaire in regard to participants suspected of having dementia. Clinical experts made diagnoses according to DSM-5 criteria. We calculated prevalence weighing the data to ensure population representativeness. RESULTS: A total of 9,930 (51.2%) of the possible 19,403 people participated, and 9,663 of these had sufficient information for analysis. Standardized prevalence of dementia and MCI was 14.6% (95% confidence interval (CI) 13.9-15.4) and 35.3% (95% CI 34.3-36.4), respectively. Dementia was more prevalent in women and MCI more prevalent in men. The most prevalent dementia subtype was Alzheimer's disease (57%). By adding data collected from a study of persons < 70 years in the same region, we estimate that there are 101,118 persons with dementia in Norway in 2020, and this is projected to increase to 236,789 and 380,134 in 2050 and 2100, respectively. CONCLUSION: We found a higher prevalence of dementia and MCI than most previous studies. The present prevalence and future projections are vital for preparing for future challenges to the healthcare system and the entire society.
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Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Feminino , Previsões , Humanos , Masculino , Testes de Estado Mental e Demência , Testes Neuropsicológicos , Noruega/epidemiologia , Prevalência , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the prevalence of cognitive and emotional impairments one year after first-ever mild stroke in younger patients Design: Prospective, observational, cohort study. SUBJECTS: A consecutive sample of 117 previously cognitively healthy patients aged 18-70 years with mild stroke (National Institutes of Health Stroke Scale score ≤ 3) were included in 2 hospitals in Norway during a 2-year period. METHODS: At 12-month follow-up, patients were assessed using validated instruments for essential cognitive domains, fatigue, depression, anxiety, apathy and pathological laughter and crying. RESULTS: In total, 78 patients (67%) had difficulty with one or a combination of the cognitive domains psychomotor speed, attention, executive and visuospatial function, and memory. Furthermore, 50 patients (43%) had impairment in either one or a combination of the emotional measures for anxiety, depressive symptoms, fatigue, apathy or emotional lability. A total of 32 patients (28%) had both cognitive and emotional impairments. Only 21 patients (18%) scored within the reference range in all the cognitive and emotional tools. CONCLUSION: Hidden impairments are common after first-ever mild stroke in younger patients. Stroke physicians should screen for hidden impairments using appropriate tools.
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Disfunção Cognitiva/psicologia , Emoções/fisiologia , Acidente Vascular Cerebral/psicologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Depressão/psicologia , Fadiga/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Adulto JovemRESUMO
Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aß42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain ß-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aß42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline.
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Envelhecimento/líquido cefalorraquidiano , Envelhecimento/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteína 1 Semelhante à Quitinase-3/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Memória , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Atrofia , Biomarcadores/líquido cefalorraquidiano , Proteína 3 Ligante de Ácido Graxo/líquido cefalorraquidiano , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Valor Preditivo dos TestesRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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OBJECTIVE: Neuroinflammation may play an important role in the pathogenesis and progression of Alzheimer disease (AD). The aim of the present study was to detect whether increased inflammatory activity at baseline could predict cognitive and functional decline in patients with amnestic mild cognitive impairment (aMCI) or AD dementia after 2 years. METHODS: Serum samples from 242 memory clinic patients with an aMCI (n=88) or AD dementia (n=154) were analyzed for C-reactive protein and for 14 other inflammatory markers [interleukin (IL)-1ß, interleukin-1 receptor antagonist, IL-6, IL-10, IL-12p40, IL-17a, IL-18, IL-22, IL-33, tumor necrosis factor, cluster of differentiation 40 ligand, interferon-γ, chemokine ligand (CCL) 2, and CCL4] by bead-based multiplex immunoassay. Disease progression was measured by the annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and annual decrease in the score on the Mini-Mental State Examination (MMSE). RESULTS: No association between increased levels of the inflammatory markers and change on the CDR-SB or MMSE score was found, but there was a significant difference in baseline IL-6 and interleukin-1 receptor antagonist levels between aMCI and AD dementia groups. CONCLUSION: Increased levels of inflammatory markers were not associated with faster progression as measured by the annual change on the CDR-SB or MMSE score.
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Doença de Alzheimer/epidemiologia , Biomarcadores/sangue , Disfunção Cognitiva/epidemiologia , Progressão da Doença , Inflamação , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Disfunção Cognitiva/sangue , Feminino , Humanos , Inflamação/sangue , Interleucinas/análise , Estudos Longitudinais , Masculino , Testes de Estado Mental e Demência/estatística & dados numéricos , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Noruega/epidemiologiaRESUMO
Psychosis (delusions or hallucinations) in Alzheimer's disease (AD + P) occurs in up to 50% of individuals and is associated with significantly worse clinical outcomes. Atypical antipsychotics, first developed for schizophrenia, are commonly used in AD + P, suggesting shared mechanisms. Despite this implication, little empirical research has been conducted to examine whether there are mechanistic similarities between AD + P and schizophrenia. In this study, we tested whether polygenic risk score (PRS) for schizophrenia was associated with AD + P. Schizophrenia PRS was calculated using Psychiatric Genomics Consortium data at ten GWAS p value thresholds (PT) in 3111 AD cases from 11 cohort studies characterized for psychosis using validated, standardized tools. Association between PRS and AD + P status was tested by logistic regression in each cohort individually and the results meta-analyzed. The schizophrenia PRS was associated with AD + P at an optimum PT of 0.01. The strongest association was for delusions where a one standard deviation increase in PRS was associated with a 1.18-fold increased risk (95% CI: 1.06-1.3; p = 0.001). These new findings point towards psychosis in AD-and particularly delusions-sharing some genetic liability with schizophrenia and support a transdiagnostic view of psychotic symptoms across the lifespan.
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Doença de Alzheimer/complicações , Herança Multifatorial , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/genética , Esquizofrenia/complicações , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/complicações , Medição de Risco , Fatores de Risco , Esquizofrenia/genéticaRESUMO
Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
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Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Locos de Características Quantitativas/genética , Adulto , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Risco , Adulto JovemRESUMO
Cortisol dysregulation has been reported in dementia and depression. Cortisol levels and its associates were investigated among older people living at home and in nursing homes, in a cross-sectional study. A sample of 650 older people, from the community (home and nursing homes) and specialized care (memory clinics and old age psychiatry wards), mean age 76.8 (SD = 10.3) (dementia n = 319, depression, n = 154, dementia plus depression n = 53, and reference group n = 124), was included. Assessment included the Mini Mental State Examination (MMSE), Cornell scale for depression in dementia, activities of daily living scales, and salivary cortisol. Number of drugs was registered. The results showed that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. Characteristics significantly associated with cortisol levels were higher MMSE score (in patients with dementia and co-morbid depression), male gender (in people with dementia), and number of medications (in the reference group). We conclude that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. The association of cortisol level with MMSE score among patients with dementia and depression could further indicate that increased stress is related to cognitive function.
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Doença de Alzheimer , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva , Valor Preditivo dos Testes , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Noruega , Proteínas tau/líquido cefalorraquidianoRESUMO
A large fraction of genetic risk factors for Alzheimer's Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer's Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10-6) from the discovery analysis for replication in an Icelandic cohort consisting of 5,341 cases and 110,008 controls. We identified a novel genomic region with genome-wide significant association with AD on chromosome 4 (combined analysis OR = 1.07, p = 2.48 x 10-8). This finding implicated HS3ST1, a gene expressed throughout the brain particularly in the cerebellar cortex. In addition, we identified IGHV1-68 in the discovery sample, previously not associated with AD. We also associated USP6NL/ECHDC3 and BZRAP1-AS1 to AD, confirming findings from a follow-up transethnic study. These new gene loci provide further evidence for AD as a polygenic disorder, and suggest new mechanistic pathways that warrant further investigation.
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Doença de Alzheimer/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Locos de Características Quantitativas , Adolescente , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between ß-amyloid (Aß) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, memory function, and depressive symptoms predicted self-reported sleep patterns in 91 cognitively healthy older adults over a 3-year period. The results showed that CSF levels of total- and phosphorylated (P) tau, and YKL-40-a marker of neuroinflammation/astroglial activation-predicted poor sleep in Aß positive older adults. Interestingly, although brain atrophy was strongly predictive of poor sleep, the relationships between CSF biomarkers and sleep were completely independent of atrophy. A joint analysis showed that unique variance in sleep was explained by P-tau and the P-tau × Aß interaction, memory function, depressive symptoms, and brain atrophy. The results demonstrate that sleep relates to a range of different pathophysiological processes, underscoring the importance of understanding its impact on neurocognitive changes in aging and people with increased risk of Alzheimer's disease.