| 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 For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy.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, 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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| 5. |
- 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
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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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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
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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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| 9. |
- Tsevis, T, et al.
(författare)
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Demographic and Clinical Characteristics of Individuals with Mild Cognitive Impairment Related to Grade of Alcohol Consumption
- 2022
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 50:5, s. 491-497
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> While alcohol overconsumption is regarded as a risk factor for Alzheimer’s disease, the specific relationship between alcohol consumption and cognitive impairment remains unclear and poorly understood. Our primary objective is to investigate whether alcohol consumption is associated with lower cognitive performance at an early phase of the development of cognitive impairment (mild cognitive impairment [MCI] stage) and second to present the clinical and demographic characteristics depending on the grade of alcohol consumption. <b><i>Methods:</i></b> This is a cross-sectional observational study, including 251 subjects with the diagnosis MCI, having caregiving contact with Memory Clinic, Karolinska University Hospital, under year 2015. We compared subgroups with different levels of alcohol consumption, concerning social parameters, cognitive, radiological, laboratory profile as well as comorbidities and burden of drugs. <b><i>Results:</i></b> Mini-mental State Examination score was not associated with alcohol consumption. Light to moderate drinkers were significantly higher educated. There were significantly more subjects using antianxiety medications among heavy drinkers in comparison with light to moderate drinkers. Finally, never/rare drinkers had significantly lower levels of erythrocyte mean corpuscular volume in their blood tests. <b><i>Discussion/Conclusion:</i></b> Alcohol consumption was not correlated with a more pronounced cognitive deficit or a distinct clinical severity at an early stage of cognitive impairment apart from higher usage of antianxiety medications. We are planning to follow up all individuals to ascertain if heavy drinkers have a different outcome compared with the other groups.
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| 10. |
- Woollacott, I. O. C., et al.
(författare)
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Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype
- 2020
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 49:1, s. 56-76
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Tidskriftsartikel (refereegranskat)abstract
- Background:Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels of glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer's disease (AD) but have not been explored in detail across the spectrum of FTD.Methods:We investigated whether CSF YKL-40 and chitotriosidase levels differed between FTD patients and controls, across different clinical and genetic subtypes of FTD, and between individuals with a clinical FTD syndrome due to AD versus non-AD (frontotemporal lobar degeneration, FTLD) pathology (based on CSF neurodegenerative biomarkers). Eighteen healthy controls and 64 people with FTD (behavioural variant FTD,n= 20; primary progressive aphasia [PPA],n= 44: nfvPPA,n= 16, svPPA,n= 11, lvPPA,n= 14, PPA-NOS,n= 3) were included. 10/64 had familial FTD, with mutations inGRN(n= 3),MAPT(n= 4), orC9orf72(n= 3). 15/64 had neurodegenerative biomarkers consistent with AD pathology. Levels were measured by immunoassay and compared using multiple linear regressions. We also examined relationships of YKL-40 and chitotriosidase with CSF total tau (T-tau), phosphorylated tau 181 (P-tau) and beta-amyloid 1-42 (A beta 42), with each other, and with age and disease du-ration.Results:CSF YKL-40 and chitotriosidase levels were higher in FTD, particularly lvPPA (both) and nfvPPA (YKL-40), compared with controls.GRNmutation carriers had higher levels of both proteins than controls andC9orf72expansion carriers, and YKL-40 was higher inMAPTmutation carriers than controls. Individuals with underlying AD pathology had higher YKL-40 and chitotriosidase levels than both controls and those with likely FTLD pathology. CSF YKL-40 and chitotriosidase levels were variably associated with levels of T-tau, P-tau and A beta 42, and with each other, depending on clinical syndrome and underlying pathology. CSF YKL-40 but not chitotriosidase was associated with age, but not disease duration.Conclusion:CSF YKL-40 and chitotriosidase levels are increased in individuals with clinical FTD syndromes, particularly due to AD pathology. In a preliminary analysis of genetic groups, levels of both proteins are found to be highly elevated in FTD due toGRNmutations, while YKL-40 is increased in individuals withMAPTmutations. As glia-derived protein levels generally correlate with T-tau and P-tau levels, they may reflect the glial response to neurodegeneration in FTLD.
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