| 1. |
- Almkvist, Ove, et al.
(författare)
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Odor Identification Across Time in Mutation Carriers and Non-Carriers in Autosomal-Dominant Alzheimer’s Disease
- 2024
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 97:2, s. 587-598
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Tidskriftsartikel (refereegranskat)abstract
- Background: Impaired odor identification is a characteristic of sporadic Alzheimer’sdisease(AD), but its presence in autosomal-dominantAD (adAD) remains uncertain. Objective: To investigate odor identification ability in mutation carriers (MC) and non-carriers (NC) of adAD in relation to years to estimated clinical onset clinical onset (YECO) of disease. Methods: Participants from six families with autosomal-dominant mutations (APP Swedish, APPArctic, and PSEN1 mutations) included 20 MC and 20 NC. The groups were comparable in age, gender, education, number of APOE ɛ4 alleles, and YECO, but differed in global cognition (Mini-Mental State Examination). The MC group included individuals in asymptomatic, symptomatic cognitively unimpaired, mild cognitive impairment, and dementia stages of disease, spanning approximately 40 years of the AD continuum. All NC were asymptomatic. Olfactory function was assessed by means of free and cued identification of common odors summarized as total identification. Results: MC performed poorer than NC in free and total identification. Four MC and none of the NC were anosmic. Olfactory functions in MC and NC were significantly and inversely related to time course (YECO) for both free and total identification. The decline in free identification began approximately 10 years prior to the estimated clinical onset of AD in MC. Odor identification proficiency was associated with episodic memory and executive function in MC and NC. Conclusions: Impaired odor identification is present well before the clinical diagnosis of AD in MC and is associated with disease progression. Odor identification ability may be a useful early biomarker for adAD.
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| 2. |
- Almkvist, Ove, et al.
(författare)
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Subcortical and Cortical Regions of Amyloid-β Pathology Measured by C-11-PiB PET Are Differentially Associated with Cognitive Functions and Stages of Disease in Memory Clinic Patients
- 2021
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 81:4, s. 1613-1624
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effect of regional brain amyloid-beta (A beta) pathology on specific cognitive functions is incompletely known.Objective: The relationship between A beta and cognitive functions was investigated in this cross-sectional multicenter study of memory clinic patients.Methods: The participants were patients diagnosed with Alzheimer's disease (AD, n = 83), mild cognitive impairment (MCI, n = 60), and healthy controls (HC, n = 32), who had been scanned by C-11-PiB PET in 13 brain regions of both hemispheres and who had been assessed by cognitive tests covering seven domains.Results: Hierarchic multiple regression analyses were performed on each cognitive test as dependent variable, controlling for demographic characteristics and APOE status (block 1) and PiB measures in 13 brain regions (block 2) as independent variables. The model was highly significant for each cognitive test and most strongly for tests of episodic memory (learning and retention) versus PiB in putamen, visuospatially demanding tests (processing and retention) versus the occipital lobe, semantic fluency versus the parietal lobe, attention versus posterior gyrus cinguli, and executive function versus nucleus accumbens. In addition, education had a positively and APOE status a negatively significant effect on cognitive tests.Conclusion: Five subcortical and cortical regions with A beta pathology are differentially associated with cognitive functions and stages of disease in memory clinic patients.
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| 3. |
- Choo, Il Han, et al.
(författare)
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Combination of f 18 fdg pet and cerebrospinal fluid biomarkers as a better predictor of the progression to alzheimer's disease in mild cognitive impairment patients
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:4, s. 929-939
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Tidskriftsartikel (refereegranskat)abstract
- The biomarker-based new diagnostic criteria have been proposed for Alzheimer's disease (AD) spectrum. However, any biomarker alone has not been known to have satisfactory AD predictability. We explored the best combination model with baseline demography, neuropsychology, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), cerebrospinal fluid (CSF) biomarkers, and apolipoprotein E (APOE) genotype evaluation to predict progression to AD in mild cognitive impairment (MCI) patients. Alongitudinal clinical follow-up (mean, 44 months; range, 1.6-161.7 months) of MCI patients was done. Among 83 MCI patients, 26 progressed to AD (MCI-AD) and 51 did not deteriorate (MCI-Stable). We applied that univariate and multivariate logistic regression analyses, and multistep model selection for AD predictors including biomarkers. In univariate logistic analysis, we selected age, Rey Auditory Verbal Retention Test, parietal glucose metabolic rate, CSF total tau, and presence or not of at least one APOE epsilon 4 allele as predictors. Through multivariate stepwise logistic analysis and model selection, we found the combination of parietal glucose metabolic rate and total tau representing the best model for AD prediction. In conclusion, our findings highlight that the combination of regional glucose metabolic assessment by PET and CSF biomarkers evaluation can significantly improve AD predictive diagnostic accuracy of each respective method.
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| 4. |
- Håkansson, Krister, 1952-, et al.
(författare)
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BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness : Associations with Working Memory Function
- 2017
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 55:2, s. 645-657
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.
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| 5. |
- Iaccarino, Leonardo, et al.
(författare)
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A Cross-Validation of FDG- and Amyloid-PET Biomarkers in Mild Cognitive Impairment for the Risk Prediction to Dementia due to Alzheimer's Disease in a Clinical Setting
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 59:2, s. 603-614
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Tidskriftsartikel (refereegranskat)abstract
- Assessments of brain glucose metabolism (F-18-FDG-PET) and cerebral amyloid burden (C-11-PiB-PET) in mild cognitive impairment (MCI) have shown highly variable performances when adopted to predict progression to dementia due to Alzheimer's disease (ADD). This study investigates, in a clinical setting, the separate and combined values of F-18-FDGPET and C-11-PiB-PET in ADD conversion prediction with optimized data analysis procedures. Respectively, we investigate the accuracy of an optimized SPM analysis for F-18-FDG-PET and of standardized uptake value ratio semiquantification for C-11-PiB-PET in predicting ADD conversion in 30 MCI subjects (age 63.57 +/- 7.78 years). Fourteen subjects converted to ADD during the follow-up (median 26.5 months, inter-quartile range 30 months). Receiver operating characteristic analyses showed an area under the curve (AUC) of 0.89 and of 0.81 for, respectively, F-18-FDG-PET and C-11-PiB-PET. F-18-FDG-PET, compared to C-11-PiB-PET, showed higher specificity (1.00 versus 0.62, respectively), but lower sensitivity (0.79 versus 1.00). Combining the biomarkers improved classification accuracy (AUC = 0.96). During the follow-up time, all the MCI subjects positive for both PET biomarkers converted to ADD, whereas all the subjects negative for both remained stable. The difference in survival distributions was confirmed by a log-rank test (p = 0.002). These results indicate a very high accuracy in predicting MCI to ADD conversion of both F-18-FDG-PET and C-11-PiB-PET imaging, the former showing optimal performance based on the SPM optimized parametric assessment. Measures of brain glucose metabolism and amyloid load represent extremely powerful diagnostic and prognostic biomarkers with complementary roles in prodromal dementia phase, particularly when tailored to individual cases in clinical settings.
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| 6. |
- Ledreux, Aurelie, et al.
(författare)
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Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum BDNF Levels in Healthy Older Adults : A Randomized Controlled Intervention Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 71:4, s. 1245-1261
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that an active lifestyle is associated with better brain health and a longer life, compared to a more sedentary lifestyle. These studies, both on human and animal subjects, have typically focused on a single activity, usually physical exercise, but other activities have received an increasing interest. One proposed mechanism is that physical exercise increases levels of brain-derived neurotrophic factor (BDNF) in the brain. For the first time, the long-term effects on serum BDNF levels were compared in persons who engaged in either physical exercise training, cognitive training, or mindfulness practice during 5 weeks, and compared with an active control group. Two cohorts of healthy older individuals, one from the Boston area in the US and one from the Vaxjo area in Sweden, participated. A total of 146 participants were randomly assigned to one of the four groups. All interventions were structurally similar, using interactive, computer-based software that directed participants to carry out specified activities for 35 minutes/day, 5 days per week for 5 weeks. Blood samples were obtained at baseline and soon after the completion of the 5-week long intervention program, and serum BDNF levels were measured using a commercially available ELISA. Only the group that underwent cognitive training increased their serum BDNF levels after 5 weeks of training (F-1,F-74 = 4.22, p = 0.044, partial eta(2) = 0.054), corresponding to an average 10% increase. These results strongly suggest that cognitive training can exert beneficial effects on brain health in an older adult population.
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| 7. |
- Leuzy, Antoine, et al.
(författare)
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Concordance and Diagnostic Accuracy of [C-11]PIB PET and Cerebrospinal Fluid Biomarkers in a Sample of Patients with Mild Cognitive Impairment and Alzheimer's Disease
- 2015
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 45:4, s. 1077-1088
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) pathology can be quantified in vivo using cerebrospinal fluid (CSF) levels of amyloid-beta(1-42) (A beta(1-42)), total-tau (t-tau), and phosphorylated tau (p- tau(181p)), as well as with positron emission tomography (PET) using [C-11]Pittsburgh compound-B ([C-11]PIB). Studies assessing concordance between these measures, however, have provided conflicting results. Moreover, it has been proposed that [C-11]PIB PET may be of greater clinical utility in terms of identifying patients with mild cognitive impairment (MCI) who will progress to the dementia phase of AD. Objective: To determine concordance and classification accuracy of CSF biomarkers and [C-11]PIB PET in a cohort of patients with MCI and AD. Methods: 68 patients (MCI, n = 33; AD, n = 35) underwent [C-11]PIB PET and CSF sampling. Cutoffs of >1.41 ([C-11]PIB), <450 pg/mL-and a more lenient cutoff of 550 pg/mL-(A beta(1-42)), <6.5 (A beta(1-42)/p-tau181p), and 1.14 (A beta(1- 42)/t-tau), were used to determine concordance. Logistic regression was used to determine classification accuracy with respect to stable MCI (sMCI) versus MCI who progressed to AD (pMCI). Results: Concordance between [C-11]PIB and A beta(1-42) was highest for sMCI (67%), followed by AD (60%) and pMCI (33%). Agreement was increased across groups using A beta(1-42) < 550 pg/mL, or A beta(1-42) to tau ratios. Logistic regression showed that classification accuracy of [11C] PIB, between sMCI and pMCI, was superior to A beta(1-42) (73% versus 58%), A beta(1-42)/t-tau (63%), and A beta(1-42)/p-tau181p (65%). Conclusion: In the present study, [C-11]PIB proved a better predictor of progression to AD in patients with MCI, relative to CSF measures of A beta(1-42) or A beta(1-42)/tau. Discordance between PET and CSF markers for A beta(1-42) suggests they cannot be used interchangeably, as is currently the case.
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| 8. |
- Li, Xiaozhen, et al.
(författare)
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The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 56:1, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Familial Alzheimer’s disease (FAD) mutations have very high penetrance but age at onset and rate of disease progression differ. Neuroimaging and cerebrospinal fluid (CSF) examinations in mutation carriers (MCs) may provide an opportunity to identify early biomarkers that can be used to track disease progression from presymptomatic to the dementia stages of disease. The default mode network (DMN) is a resting state neuronal network composed of regions known to associate with amyloid deposition in AD. We hypothesized that functional connectivity in the DMN might change at pre-clinical stages in FAD MCs and correlate with changes in CSF biomarkers as a consequence of AD brain pathology. To test the hypothesis, we compared the functional connectivity in DMN between pre-MCs/MCs and non-carriers (NCs). No significant differences between pre-MCs and NCs were observed. When comparing all MCs with NCs, significant decreased functional connectivity in the right inferior parietal lobule, right precuneus, and left posterior cingulate cortex were found. We also found statistically significant correlations between CSF amyloid-β 42 and tau protein levels and average Z-score, a resting-state functional MRI measurement reflecting the degree of the correlation between a given voxel’s time courses and the time courses corresponding to DMN, from the region with statistical difference. The observed disruption of DMN and pathological levels of AD CSF-biomarkers in FAD MCs are similar to the changes described in sporadic AD, which give further support that amyloid and tau pathology impairs neuronal and synaptic function.
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| 9. |
- Petrazzuoli, Ferdinando, et al.
(författare)
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Brief Cognitive Tests Used in Primary Care Cannot Accurately Differentiate Mild Cognitive Impairment from Subjective Cognitive Decline
- 2020
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 75:4, s. 1191-1201
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differentiating mild cognitive impairment (MCI) from subjective cognitive decline (SCD) is important because of the higher progression rate to dementia for MCI and when considering future disease-modifying drugs that will have treatment indications at the MCI stage. Objective: We examined if the two most widely-used cognitive tests, the Mini-Mental State Examination (MMSE) and clock-drawing test (CDT), and a test of attention/executive function (AQT) accurately can differentiate MCI from SCD. Methods: We included 466 consecutively recruited non-demented patients with cognitive complaints from the BioFINDER study who had been referred to memory clinics, predominantly from primary care. They were classified as MCI (n = 258) or SCD (n = 208) after thorough neuropsychological assessments. The accuracy of MMSE, CDT, and AQT for identifying MCI was examined both in training and validation samples and in the whole population. Results: As a single test, MMSE had the highest accuracy (sensitivity 73%, specificity 60%). The best combination of two tests was MMSE < 27 points or AQT > 91 seconds (sensitivity 56%, specificity 78%), but in logistic regression models, their AUC (0.76) was not significantly better than MMSE alone (AUC 0.75). CDT and AQT performed significantly worse (AUC 0.71; p < 0.001-0.05); otherwise no differences were seen between any combination of two or three tests. Conclusion: Neither single nor combinations of tests could differentiate MCI from SCD with adequately high accuracy. There is a great need to further develop, validate, and implement accurate screening-tests for primary care to improve accurate identification of MCI among individuals that seek medical care due to cognitive symptoms.
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| 10. |
- Schöll, Michael, et al.
(författare)
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Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers
- 2011
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 24:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- Studies in carriers of mutations that cause early-onset familial Alzheimer's disease (eoFAD) are of significant interest. We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1 (PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with (18)F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group of 27 sporadic Alzheimer's disease (sAD) patients. This decline correlated with cognitive deterioration over time as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of 249 sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by (18)F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.
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