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- Alenius, M, et al.
(författare)
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Cognitive Performance among Cognitively Healthy Adults Aged 30-100 Years
- 2019
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 9:1, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> To detect cognitive decline in older adults, measures of verbal fluency and verbal memory are widely used. Less is known about performance in these measures in younger persons or according to education level and gender. We investigated cognitive performance according to age, education and gender among cognitively healthy adults aged 30–100 years. <b><i>Methods:</i></b> The study population comprised 4,174 cognitively healthy persons participating in the nationally representative Finnish Health 2011 survey. Cognitive assessment included verbal fluency, word list memory, word list recall and word list savings from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. <b><i>Results:</i></b> Total variance in the cognitive test performance explained by age, education and gender varied from 12.3 to 31.2%. A decreasing trend in cognitive performance existed in all subtests by advancing age, with differences appearing between 50 and 55 years. Persons with the highest-education level performed best for all measures. For the participants < 55 years, education explained part of the variance, while age and gender did not. <b><i>Conclusions:</i></b> When assessing cognition, age and education should be accounted for in more detail in research and clinical practice. Additionally, the cohort effect and its potential impact on the renewal cycle of future normative values for cognitive tests should be considered.
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| 2. |
- Alenius, M, et al.
(författare)
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Cognitive Performance at Time of AD Diagnosis: A Clinically Augmented Register-Based Study
- 2022
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Ingår i: Frontiers in psychology. - : Frontiers Media SA. - 1664-1078. ; 13, s. 901945-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer’s disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010–2013 (aged 60–81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.
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| 3. |
- Alenius, M, et al.
(författare)
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Education-Based Cutoffs for Cognitive Screening of Alzheimer's Disease
- 2022
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 51:1, s. 42-55
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. <b><i>Methods:</i></b> CERAD-nb scores were obtained from AD patients (<i>n</i> = 389, 58% women, mean age 74.0 years) and from controls (<i>n</i> = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. <b><i>Results:</i></b> Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. <b><i>Conclusions:</i></b> Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.
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| 4. |
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| 5. |
- Konte, B, et al.
(författare)
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HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry
- 2021
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 214-
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Tidskriftsartikel (refereegranskat)abstract
- The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E−06) and agranulocytosis (OR = 10.49, P = 1.83E−06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E−08; agranulocytosis: OR = 16.31, P = 1.39E−06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.
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| 8. |
- Orešič, Matej, 1967-, et al.
(författare)
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Metabolome in progression to Alzheimer's disease
- 2011
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Ingår i: Translational Psychiatry. - New York : Nature Publishing Group. - 2158-3188. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.
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| 9. |
- Wesenhagen, K. E. J., et al.
(författare)
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Effects of age, amyloid, sex, and APOE epsilon 4 on the CSF proteome in normal cognition
- 2022
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E sigma 4 genotype. Methods We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery, and Metabolic Syndrome in Men. In total, 1149 proteins were measured with liquid chromatography mass spectrometry with multiple reaction monitoring/Rules-Based Medicine, tandem mass tag mass spectrometry, and SOMAscan. We tested associations between age and protein levels in linear models and tested enrichment for Reactome pathways. Results Levels of 252 proteins increased with age independently of amyloid status. These proteins were associated with immune and signaling processes. Levels of 21 proteins decreased with older age exclusively in amyloid abnormal participants and these were enriched for extracellular matrix organization. Discussion We found amyloid-independent and -dependent CSF proteome changes with older age, perhaps representing physiological aging and early AD pathology.
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