| 1. |
- 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 For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy.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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| 2. |
- Borda, MG, et al.
(författare)
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Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness
- 2022
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 51:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). <b><i>Methods:</i></b> This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer’s Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. <b><i>Results:</i></b> The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. <b><i>Discussion/Conclusion:</i></b> TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.
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| 3. |
- Engedal, K, et al.
(författare)
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The Power of EEG to Predict Conversion from Mild Cognitive Impairment and Subjective Cognitive Decline to Dementia
- 2020
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 49:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). <b><i>Methods:</i></b> From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. <b><i>Results:</i></b> Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer’s disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70–0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. <b><i>Conclusion:</i></b> We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods.
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| 4. |
- Fresnais, David, 1995-, et al.
(författare)
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Cerebrovascular Hemodynamics in Cognitive Impairment and Dementia : A Systematic Review and Meta-Analysis of Transcranial Doppler Studies
- 2023
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 52:5-6, s. 277-295
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Transcranial Doppler sonography (TCD) is a non-invasive tool for measuring cerebrovascular hemodynamics. Studies have reported alterations in cerebrovascular hemodynamics in normal aging, mild cognitive impairment (MCI) and dementia, as well as in different etiologies of dementia. This systematic review and meta-analysis was designed to investigate the relationship between cerebral blood velocity (CBv) and pulsatility index (PI) in the middle cerebral artery (MCA) in persons with MCI and dementia.Methods: A systematic literature search was conducted in Pubmed, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL. The search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of 33439 articles, 86 were reviewed in full-text, and 35 fulfilled the inclusion criteria.Results: CBv was significantly lower and PI significantly higher in MCA in vascular dementia (VaD) and Alzheimer's disease (AD) compared to cognitively normal (CN) older persons. Also, CBv was lower in MCI compared to CN. There were no significant differences in CBv in MCA in AD compared with VaD, although PI was higher in VaD compared to AD.Conclusion: Alterations in cerebrovascular hemodynamics are seen in AD, VaD and MCI. While PI was slightly higher in VaD compared to AD, the reduction in CBv appears to be equally pronounced across neurodegenerative and vascular etiologies of dementia.
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| 5. |
- Fresnais, David, et al.
(författare)
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The Association between Carotid Intima-Media Thickness and Cognitive Impairment : A Systematic Review and Meta-Analysis
- 2021
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 50:4, s. 305-317
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Forskningsöversikt (refereegranskat)abstract
- Background: Emerging evidence suggests that cognitive impairment (CI) and different etiologies of dementia, including Alzheimer's disease (AD), are associated with vascular risk factors and atherosclerosis. In clinical practice, carotid intima-media thickness (CIMT) measured by ultrasonography may be a marker of atherosclerosis. Many studies report increased CIMT in patients with dementia and CI although a firm association has not yet been established.Aim: This systematic review and meta-analysis were conducted to study the relationship between CIMT, dementia, and CI.Methods: The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included the following databases: Medline, Embase, Cochrane Library, and Epistemonikos. The search spanned from 2000 to 2020 and was limited to English and Scandinavian languages.Results: The main analysis of CIMT in subjects with CI compared to subjects with no cognitive impairment (NCI) included 12 studies; 1,089 subjects with CI and 5,223 with NCI. There was no significant difference in CIMT between the CI and NCI groups. However, subgroup analyses revealed significantly higher CIMT in the mild cognitive impairment (MCI) and dementia groups than the NCI group. In addition, patients with dementia had increased CIMT compared to patients with MCI, and patients with AD demonstrated higher CIMT than those with vascular cognitive impairment (VCI).Conclusion: CIMT may be higher in subjects with CI than in cognitively healthy subjects although no significant difference was observed in our main analysis. CIMT was higher in the dementia group than the MCI group and in the AD group compared to the VCI group.
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| 6. |
- Gerards, M., et al.
(författare)
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Alzheimer's Disease Plasma Biomarkers Distinguish Clinical Diagnostic Groups in Memory Clinic Patients
- 2022
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 51:2, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed. Methods: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Ass42), amyloid-beta40 (Ass40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed. Results: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Ass42/Ass40 (H(2) = 7.50, p = 0.02) and pTau181/Ass42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Ass42 and an SCD versus MCI difference for Ass42/Ass40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Ass42, Ass40, and NFL concentrations. Conclusion: Plasma pTau181 and NFL, as well as the ratios Ass42/Ass40 and pTau181/Ass42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies.
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| 7. |
- Grande, Giulia, et al.
(författare)
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Detection and Prediction of Incident Alzheimer Dementia over a 10-Year or Longer Medical History : A Population-Based Study in Primary Care
- 2020
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 49, s. 384-389
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the crucial role played by general practitioners in the identification and care of people with cognitive impairment, few data are available on how they may improve the early recognition of patients with Alzheimer dementia (AD), especially those with long (i.e., 10 years and longer) medical history. Aims: To investigate the occurrence and the predictors of AD during a 10-year or longer period prior AD diagnosis in primary care patients aged 60 years or older. Materials and Methods: A cohort study with a nested case-control analysis has been conducted. Data were extracted from the Italian Health Search Database (HSD), an Italian database with primary care data. AD cases have been defined in accordance with the International Classification of Diseases, ninth edition (ICD-9-CM) codes and coupled with the use of anti-dementia drugs. Prevalence and incidence rates of AD have been calculated. To test the association between candidate predictors, being identified in a minimum period of 10 years, and incident cases of AD, we used a multivariate conditional logistic regression model. Results: As recorded in the primary care database, AD prevalence among patients aged 60 years or older was 0.8% during 2016, reaching 2.4% among nonagenarians. Overall, 1,889 incident cases of AD have been identified, with an incidence rate as high as 0.09% person-year. Compared with 18,890 matched controls, history of hallucinations, agitation, anxiety, aberrant motor behavior, and memory deficits were positively associated with higher odds of AD (p < 0.001 for all) diagnosis. A previous diagnosis of depression and diabetes and the use of low-dose aspirin and non-steroidal anti-inflammatory drugs were associated with higher odds of AD (p < 0.05 for all). Conclusion: Our findings show that, in accordance with primary care records, 1% of patients aged 60 years and older have a diagnosis of AD, with an incident AD diagnosis of 0.1% per year. AD is often under-reported in primary care settings; yet, several predictors identified in this study may support general practitioners to early identify patients at risk of AD.
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| 8. |
- Li, Yuanjing, et al.
(författare)
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Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education : A Population-Based Cohort Study
- 2023
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Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008 .- 1421-9824. ; 52:4, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60–74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.
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| 9. |
- Overton, Marieclaire, et al.
(författare)
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Diagnostic Stability of Mild Cognitive Impairment, and Predictors of Reversion to Normal Cognitive Functioning
- 2020
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 48:5-6, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Studies that investigate predictive factors for spontaneous recovery (reversion) from mild cognitive impairment (MCI) are only beginning to emerge, and the long-term course of MCI is not properly understood. We aimed to investigate stability of the MCI diagnosis, predictors for reversion, as well as the trajectory of MCI over the course of 12 years. Materials and Methods: Data were drawn from the Swedish population study: Good Aging in Skåne with MCI defined according to the expanded Mayo Clinic criteria. A total of 331 participants, aged 60-95 years with MCI, were used to investigate 6-year MCI stability and reversion, and 410 participants were used to inspect 12-year MCI trajectory. Predictors for reversion included demographical factors, psychological status, and factors tied to the cognitive testing session and the operationalization of the MCI criteria. Results: Over half (58%, 95% CI 52.7-63.3) of the participants reverted back to normal cognitive functioning at 6-year follow-up. Of those with stable MCI, 56.5% (95% CI 48.2-64.8) changed subtype. A total of 23.9% (95% CI 13.7-34.1) of the 6-year follow-up reverters re-transitioned back to MCI at 12-year follow-up. ORs for reversion were significantly higher in participants with lower age (60-year-olds: OR 2.19, 95% CI 1.08-4.43, 70-year-olds: OR 3.11, 95% CI 1.27-7.62), better global cognitive functioning (OR 1.15, 95% CI 1.03-1.29), good concentration (OR 2.53, 95% CI 1.06-6.05), and single-domain subtype (OR 2.68, 95% CI 1.51-4.75). Conclusion: Our findings provide further support that MCI reversion to normal cognitive functioning as well as re-transitioning to MCI is fairly common, suggesting that the MCI trajectory does not necessarily lead straight to dementia. Additionally, assessment of factors associated with reversion can aid clinicians to make accurate MCI progression prognosis.
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| 10. |
- Peters, R., et al.
(författare)
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Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis
- 2021
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 50, s. 318-325
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.
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