| 1. |
- Nordberg, Agneta, et al.
(författare)
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A European multicentre PET study of fibrillar amyloid in Alzheimer's disease
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:1, s. 104-114
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer's disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies. In this study 238 [C-11]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [C-11]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 +/- 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 +/- 8 years) and 51 healthy controls (mean age 67.4 +/- 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 +/- 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype. [C-11]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [C-11]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [C-11]PIB retention was observed in MCI ApoE epsilon 4 carriers compared to non-ApoE epsilon 4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted. This study demonstrated the robustness of [C-11]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.
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| 2. |
- Rauhala, Elina, et al.
(författare)
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Change in brain amyloid load and cognition in patients with amnestic mild cognitive impairment : a 3-year follow-up study
- 2022
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Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Our aim was to investigate the discriminative value of 18F-Flutemetamol PET in longitudinal assessment of amyloid beta accumulation in amnestic mild cognitive impairment (aMCI) patients, in relation to longitudinal cognitive changes.Methods: We investigated the change in 18F-Flutemetamol uptake and cognitive impairment in aMCI patients over time up to 3 years which enabled us to investigate possible association between changes in brain amyloid load and cognition over time. Thirty-four patients with aMCI (mean age 73.4 years, SD 6.6) were examined with 18F-Flutemetamol PET scan, brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to Alzheimer´s disease (AD). 18F-Flutemetamol data were analyzed both with automated region-of-interest analysis and voxel-based statistical parametric mapping.Results: 18F-flutemetamol uptake increased during the follow-up, and the increase was significantly higher in patients who were amyloid positive at baseline as compared to the amyloid-negative ones. At follow-up, there was a significant association between 18F-Flutemetamol uptake and MMSE, logical memory I (immediate recall), logical memory II (delayed recall) and verbal fluency. An association was seen between the increase in 18F-Flutemetamol uptake and decline in MMSE and logical memory I scores.Conclusions: In the early phase of aMCI, presence of amyloid pathology at baseline strongly predicted amyloid accumulation during follow-up, which was further paralleled by cognitive declines. Inversely, some of our patients remained amyloid negative also at the end of the study without significant change in 18F-Flutemetamol uptake or cognition. Future studies with longer follow-up are needed to distinguish whether the underlying pathophysiology of aMCI in such patients is other than AD.
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| 3. |
- Toppala, Sini, et al.
(författare)
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Midlife Insulin Resistance as a Predictor for Late-Life Cognitive Function and Cerebrovascular Lesions
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 72:1, s. 215-228
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type 2 diabetes (T2DM) increases the risk for Alzheimer’s disease (AD) but not for AD neuropathology. The association between T2DM and AD is assumed to be mediated through vascular mechanisms. However, insulin resistance (IR), the hallmark of T2DM, has been shown to associate with AD neuropathology and cognitive decline.Objective: To evaluate if midlife IR predicts late-life cognitive performance and cerebrovascular lesions (white matter hyperintensities and total vascular burden), and whether cerebrovascular lesions and brain amyloid load are associated with cognitive functioning.Methods: This exposure-to-control follow-up study examined 60 volunteers without dementia (mean age 70.9 years) with neurocognitive testing, brain 3T-MRI and amyloid-PET imaging. The volunteers were recruited from the Finnish Health 2000 survey (n = 6062) to attend follow-up examinations in 2014–2016 according to their insulin sensitivity in 2000 and their APOE genotype. The exposure group (n = 30) had IR in 2000 and the 30 controls had normal insulin sensitivity. There were 15 APOE ɛ4 carriers per group. Statistical analyses were performed with multivariable linear models.Results: At follow-up the IR+group performed worse on executive functions (p = 0.02) and processing speed (p = 0.007) than the IR- group. The groups did not differ in cerebrovascular lesions. No associations were found between cerebrovascular lesions and neurocognitive test scores. Brain amyloid deposition associated with slower processing speed.Conclusion: Midlife IR predicted poorer executive functions and slower processing speed, but not cerebrovascular lesions. Brain amyloid deposition was associated with slower processing speed. The association between midlife IR and late-life cognition might not be mediated through cerebrovascular lesions measured here.
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