| 1. |
- Eckerström, Marie, 1981, et al.
(författare)
-
Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.
- 2017
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:8, s. 96-107
-
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.
|
|
| 2. |
- Hessen, Erik, et al.
(författare)
-
Subjective Cognitive Impairment Is a Predominantly Benign Condition in Memory Clinic Patients Followed for 6 Years: The Gothenburg-Oslo MCI Study.
- 2017
-
Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 7:1, s. 1-14
-
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.
|
|
| 3. |
- Hessen, E., et al.
(författare)
-
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
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 47:3, s. 619-628
-
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.
|
|
| 4. |
- Wallin, Anders, 1950, et al.
(författare)
-
Alzheimer's disease-subcortical vascular disease spectrum in a hospital-based setting: overview of results from the Gothenburg MCI and dementia studies.
- 2016
-
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
-
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.
|
|
| 5. |
- Wallin, Anders, 1950, et al.
(författare)
-
The Gothenburg MCI study: design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.
- 2016
-
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
-
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.
|
|
| 6. |
- Eckerström, Marie, 1981, et al.
(författare)
-
High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment
- 2016
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 42:1-2, s. 93-105
-
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.
|
|
| 7. |
- Göthlin, Mattias, 1978, et al.
(författare)
-
Prognostic Accuracy of Mild Cognitive Impairment Subtypes at Different Cut-Off Levels.
- 2017
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 43:5-6, s. 330-341
-
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.
|
|
| 8. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
Biomarkers in relation to cognitive reserve in patients with mild cognitive impairment--proof of concept.
- 2009
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:2, s. 194-200
-
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.
|
|
| 9. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
Cognitive reserve in relation to abeta42 in patients converting from MCI to dementia - a follow-up report.
- 2009
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:2, s. 110-5
-
Tidskriftsartikel (refereegranskat)abstract
- The concept of the cognitive reserve (CR) hypothesizes that premorbid factors such as education enable compensation for the manifestation of brain pathology. Accordingly, pathology should be more prominent in individuals with higher CR before becoming clinically apparent. Previously, we found that patients subsequently converting to dementia with higher CR had lower concentrations of amyloid beta 42 (abeta42) as compared to patients with lower CR. However, the interaction between time, biomarkers, neuropsychological performance and CR is yet to be established. OBJECTIVE: To study the relation between biomarkers, neuropsychological performance and CR longitudinally. METHOD: A mixed between-within subject analysis of variance was performed for longitudinal analysis. Paired t tests were used for within group comparisons. RESULTS: Patients with higher CR (n = 15) had significantly lower concentrations of abeta42 at both time points compared to those with medium (n = 23) and lower CR (n = 28). Also, abeta42 concentrations decreased significantly from baseline to follow-up in patients with higher and medium CR. Groups performed comparably on neuropsychological tests. CONCLUSION: This study provides further support for the applicability of abeta42 as a substitute for pathology in relation to CR. Also, abeta42 reflects the disease progression in patients with higher and medium CR.
|
|
| 10. |
- Rolstad, Sindre, 1976, et al.
(författare)
-
High Education May Offer Protection Against Tauopathy in Patients with Mild Cognitive Impairment.
- 2010
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 21:1, s. 221-8
-
Tidskriftsartikel (refereegranskat)abstract
- The concepts of brain and cognitive reserve stem from the observation that premorbid factors (e.g., education) result in variation in the response to brain pathology. Potential early influence of reserve on pathology, as assessed using the cerebrospinal fluid biomarkers total tau and amyloid-beta{42}, and cognition was explored in mild cognitive impairment (MCI) patients who remained stable over a two-year period. A total of 102 patients with stable MCI grouped on the basis of educational level were compared with regard to biomarker concentrations and cognitive performance. Stable MCI patients with higher education had lower concentrations of t-tau as compared to those with lower education. Also, educational level predicted a significant proportion of the total variance in t-tau concentrations. Our results suggest that higher education may offer protection against tauopathy.
|
|
