| 1. |
- Eckerström, Carl, et al.
(författare)
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Characteristic Biomarker and Cognitive Profile in Incipient Mixed Dementia.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 73:2, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Research has shown that mixed dementia is more common than previously believed but little is known of its early stages.To examine if incipient mixed dementia can be differentiated from incipient Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SVD) using neuropsychological tests, cerebrospinal fluid (CSF) markers, and magnetic resonance imaging markers.We included 493 patients and controls from the Gothenburg MCI study and used the dementia groups for marker selection (CSF total-tau (T-tau), phospho-tau (P-tau), and amyloid-β42 (Aβ42), 11 neuropsychological tests, and 92 regional brain volumes) and to obtain cut-off values which were then applied to the MCI groups.Incipient mixed dementia was best differentiated from incipient AD by the Word fluency F-A-S test and the Trail making test A. CSF T-tau, P-tau, and Aβ42 differentiated incipient mixed dementia from incipient SVD.Incipient mixed dementia is characterized by an AD-like biomarker profile and an SVD-like cognitive profile. Incipient mixed dementia can be separated from incipient AD and incipient SVD using CSF markers and cognitive testing.
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| 2. |
- Eckerström, Carl, et al.
(författare)
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High white matter lesion load is associated with hippocampal atrophy in mild cognitive impairment.
- 2011
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 31:2, s. 132-8
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is a heterogeneous condition suggested as a prodromal state of Alzheimer's disease (AD) and subcortical vascular dementia (SVD). Recent findings suggest that white matter lesions (WML) may be associated with hippocampal atrophy. The objective of the study was to examine hippocampal and WML volumes in MCI patients and to examine if WML were linked to hippocampal atrophy.
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| 3. |
- Eckerström, Marie, 1981, et al.
(författare)
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Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:8, s. 96-107
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Tidskriftsartikel (refereegranskat)abstract
- Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications.Memory clinic patients (n = 235) were classified as SCD (n = 122): subtle cognitive decline (n = 36) and mild cognitive impairment (n = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications.Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2.In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.
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| 4. |
- Eckerström, Marie, 1981, et al.
(författare)
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Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q) - a research tool discriminating between subjectively cognitively impaired patients and healthy controls.
- 2013
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Ingår i: International psychogeriatrics / IPA. - 1741-203X. ; 25:3, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: Subjective cognitive impairment (SCI) is a potential early marker for actual cognitive decline. The cognitive manifestation of the SCI stage is, however, largely unknown. Self-report instruments developed especially for use in the SCI population are lacking, and many SCI studies have not excluded mild cognitive impairment and dementia. We developed and tested a patient-based questionnaire on everyday cognitive function aiming to discriminate between patients with subjective, but not objective, cognitive impairment and healthy controls. Methods: Individuals experiencing cognitive impairment were interviewed to generate a pool of items. After condensing to 97 items, we tested the questionnaire in 93 SCI patients seeking care at a memory clinic (age M = 64.5 years, Mini-Mental State Examination (MMSE) M = 29.0) and 50 healthy controls (age M = 69.6 years, MMSE M = 29.3). Further item reduction was conducted to maximize that remaining items would discriminate between SCI patients and controls, using a conservative α level and requiring medium to high effect sizes. Internal consistency reliability and convergent validity was subsequently examined. Results: Forty-five items discriminated between the groups, resulting in the Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire (SASCI-Q). Internal consistency was high and correlations to a single question on memory functioning were of medium to large sizes. Most remaining items were related to the memory domain. Conclusion: The SASCI-Q discriminates between SCI patients and healthy controls and demonstrates satisfying psychometric properties. The instrument provides a research method for examining SCI and forms a foundation for future examining which SCI symptoms predict objective cognitive decline. The cognitive manifestation of the SCI stage is mostly related to experiences of memory deficits.
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| 7. |
- Göthlin, Mattias, 1978
(författare)
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Mild cognitive impairment - concepts, cut-offs, and clinical relevance
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mild cognitive impairment (MCI) is a diagnosis frequently used in dementia research and in memory clinics. MCI is meant to identify patients without dementia, but with cognitive decline beyond what is considered normal, and with an increased risk of progressing to dementia. Typically, cognitive test performance 1.5 standard deviations (SD) or more below normal controls is considered impaired. To account better for heterogeneity in etiology and prognosis in MCI, clinical subtypes of MCI have been suggested; MCI with or without memory impairment as one dimension, and impairment in one or more than one cognitive domain as another dimension. The aim of this thesis is to clarify the prognostic value of MCI and MCI subtypes in memory-clinic patients. All participants in papers I-III were either patients seeking care at the Sahlgrenska memory clinic in Mölndal, or healthy controls examined at the same unit. Paper I included 317 patients, 55 of whom progressed to dementia. Paper II included 358 patients, 68 of whom progressed to dementia. Paper III included 383 patients, 70 of whom progressed to dementia. All patients included in paper I were also included in papers II and III, all patients included in paper II were also included in paper III. In paper I, 317 patients were followed for 2 years, and 168 patients were followed for 4-6 years. The probability of a patient progressing to dementia after 2 years was 17%, and 14% after 4-6 years. One-third of the memory- clinic patients did not meet standard criteria for MCI at baseline, and had a reduced probability of progressing to dementia (from 17% to 1% within 2 years and from 14% to 9% after 4-6 years). Meeting standard criteria for MCI only slightly increased the risk of progressing to dementia (from 17% to 26% after 2 years and from 14% to 20% after 4-6 years). Amnestic multi-domain MCI was the only subtype that significantly increased a patient’s probability of progressing to dementia (from 18% to 46% after 2 years and from 14% to 37% after 4-6 years). A more liberal MCI cut-off (i.e. 1.0 SD instead of 1.5 SD or 2.0 SD) did not improve the prognostic accuracy of MCI or the MCI subtypes. In paper II, amnestic multi-domain MCI was associated with a much larger increase in probability of progression to dementia in younger patients under 65 with more than 12 years of education than in other demographic groups, as compared with patients with other subtypes and those who did not meet MCI criteria. In paper III, cognitive subtypes derived from a latent profile analysis differentiated between patients who two years after baseline progressed to Alzheimer's disease dementia vs. dementia with subcortical vascular features, where the traditional MCI subtypes did not. In conclusion, a large group of memory-clinic patients do not display significant cognitive impairments and have a very low probability of progressing to dementia. Prognosticating progression to dementia is easier in younger patients with more years of education than in other demographic groups. However, even among younger patients with more years of education, it may be better to use absence of amnestic multi-domain MCI to rule out progression to dementia, than to use presence of amnestic multi- domain MCI to find patients who will progress. Statistically derived cognitive subtypes may separate the risk of AD dementia from the risk of dementia with subcortical vascular features where the established MCI subtypes do not.
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| 8. |
- Göthlin, Mattias, 1978, et al.
(författare)
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Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels.
- 2017
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 43:5-6, s. 330-341
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic accuracy of mild cognitive impairment (MCI) in clinical settings is debated, variable across criteria, cut-offs, subtypes, and follow-up time. We aimed to estimate the prognostic accuracy of MCI and the MCI subtypes for dementia using three different cut-off levels.Memory clinic patients were followed for 2 (n = 317, age 63.7 ± 7.8) and 4-6 (n = 168, age 62.6 ± 7.4) years. We used 2.0, 1.5, and 1.0 standard deviations (SD) below the mean of normal controls (n = 120, age 64.1 ± 6.6) to categorize MCI and the MCI subtypes. Prognostic accuracy for dementia syndrome at follow-up was estimated.Amnestic multi-domain MCI (aMCI-md) significantly predicted dementia under all conditions, most markedly when speed/attention, language, or executive function was impaired alongside memory. For aMCI-md, sensitivity increased and specificity decreased when the cut-off was lowered from 2.0 to 1.5 and 1.0 SD. Non-subtyped MCI had a high sensitivity and a low specificity.Our results suggest that aMCI-md is the only viable subtype for predicting dementia for both follow-up times. Lowering the cut-off decreases the positive predictive value and increases the negative predictive value of aMCI-md. The results are important for understanding the clinical prognostic utility of MCI, and MCI as a non-progressive disorder.
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| 9. |
- Hessen, Erik, et al.
(författare)
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Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
- 2017
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 7:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In the quest for prevention or treatment, there is a need to find early markers for preclinical dementia. This study observed memory clinic patients with subjective cognitive impairment (SCI) and normal cognitive function at baseline. The primary aim was to address SCI as a potential risk factor for cognitive decline. The secondary aim was to address a potential relation between (1) baseline cerebrospinal fluid biomarkers and (2) a decline in memory performance over the first 2 years of follow-up, with a possible cognitive decline after 6 years.Eighty-one patients (mean age 61 years) were recruited from university memory clinics and followed up for 6 years.Eighty-six percent of the cohort remained cognitively stable or improved, 9% developed mild cognitive impairment, and only 5% (n = 4) developed dementia. Regression analysis revealed that low levels of Aβ42 at baseline and memory decline during the first 2 years predicted dementia. When combined, these variables were associated with a 50% risk of developing dementia.Cognitive stability for 86% of the cohort suggests that SCI is predominantly a benign condition with regard to neuropathology. The low number of individuals who developed dementia limits the generalizability of the results and discussion of progression factors.
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| 10. |
- Hessen, E., et al.
(författare)
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T-Tau is Associated with Objective Memory Decline over Two Years in Persons Seeking Help for Subjective Cognitive Decline: A Report from the Gothenburg-Oslo MCI Study
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 47:3, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 - IOS Press and the authors. All rights reserved. Background: There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. Objective: The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. Methods: 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. Results: The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable.Tthe baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years.Tthe general trend for the whole group was improved memory and executive test scores.Tthere were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. Conclusions: The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.
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