| 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, 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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| 3. |
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| 4. |
- Wallin, Anders, 1950, et al.
(författare)
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Alzheimer's disease-subcortical vascular disease spectrum in a hospital-based setting: overview of results from the Gothenburg MCI and dementia studies.
- 2016
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 95-113
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Forskningsöversikt (refereegranskat)abstract
- The ability to discriminate between Alzheimer's disease (AD), subcortical vascular disease, and other cognitive disorders is crucial for diagnostic purposes and clinical trial outcomes. Patients with primarily subcortical vascular disease are unlikely to benefit from treatments targeting the AD pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment (MCI) and dementia studies are prospective, observational, single-center cohort studies suitable for both cross-sectional and longitudinal analysis that outline the cognitive profiles and biomarker characteristics of patients with AD, subcortical vascular disease, and other cognitive disorders. The studies, the first of which started in 1987, comprise inpatients with manifest dementia and patients seeking care for cognitive disorders at an outpatient memory clinic. This article gives an overview of the major published papers (neuropsychological, imaging/physiology, and neurochemical) of the studies including the ongoing Gothenburg MCI study. The main findings suggest that subcortical vascular disease with or without dementia exhibit a characteristic neuropsychological pattern of mental slowness and executive dysfunction and neurochemical deviations typical of white matter changes and disturbed blood-brain barrier function. Our findings may contribute to better healthcare for this underrecognized group of patients. The Gothenburg MCI study has also published papers on multimodal prediction of dementia, and cognitive reserve.Journal of Cerebral Blood Flow & Metabolism advance online publication, 29 July 2015; doi:10.1038/jcbfm.2015.148.
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| 5. |
- Wallin, Anders, 1950, et al.
(författare)
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The Gothenburg MCI study: design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.
- 2016
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Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 114-131
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for increased nosological knowledge to enable rational trials in Alzheimer's disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD+SVD=MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials.Journal of Cerebral Blood Flow & Metabolism advance online publication, 15 July 2015; doi:10.1038/jcbfm.2015.147.
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| 6. |
- Eckerström, Marie, 1981, et al.
(författare)
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High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment
- 2016
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 42:1-2, s. 93-105
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). Methods: Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. Results: Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. Conclusion: Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI.
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| 7. |
- 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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| 8. |
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| 9. |
- 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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| 10. |
- Rolstad, Sindre, 1976, et al.
(författare)
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Biomarkers in relation to cognitive reserve in patients with mild cognitive impairment--proof of concept.
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:2, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of the cognitive reserve (CR) posits that factors such as education enable compensation for the effect of brain pathology. Consequently, pathology should be more pronounced in individuals with higher CR before becoming clinically apparent. Biomarkers such as total tau (t-tau) and beta-amyloid 42 (Abeta42) may be surrogates for pathology in relation to CR in patients with neurodegenerative disease. OBJECTIVE: To examine the applicability of biomarkers as surrogates for pathology in relation to the CR in patients with mild cognitive impairment (MCI) either converting to dementia or remaining stable at follow-up. METHOD: Comparisons of baseline t-tau, Abeta42, educational years and global cognition for MCI patients either converting to dementia (n = 57) or remaining stable (n = 91) were made. Patients converting to dementia were grouped on the basis of educational level and compared considering biomarkers and neuropsychological tests. RESULTS: Stable MCI patients were better educated, performed better cognitively, had higher Abeta42 levels and lower levels of t-tau. Converting MCI patients with higher education had lower levels of Abeta42 and performed equally in neuropsychological tests compared to those with lower education. CONCLUSION: Our results suggest that highly educated MCI patients subsequently converting to dementia display more amyloid pathology.
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