| 1. |
- Orešič, Matej, 1967-, et al.
(författare)
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Metabolome in progression to Alzheimer's disease
- 2011
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Ingår i: Translational Psychiatry. - New York : Nature Publishing Group. - 2158-3188. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.
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| 2. |
- Tukiainen, T., et al.
(författare)
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Mild cognitive impairment associates with concurrent decreases in serum cholesterol and cholesterol-related lipoprotein subclasses
- 2012
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 16:7, s. 631-635
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Accumulating evidence suggests that serum lipids are associated with cognitive decline and dementias. However, majority of the existing information concerns only serum total cholesterol (TC) and data at the level of lipoprotein fractions and subclasses is limited. The aim of this study was to explore the levels and trends of main cholesterol and triglyceride measures and eight lipoprotein subclasses during normal aging and the development of mild cognitive impairment by following a group of elderly for six years. Design: Longitudinal. Setting: City of Kuopio, Finland. Participants: 45 elderly individuals of which 20 developed mild cognitive impairment (MCI) during the follow-up. Measurement: On each visit participants underwent an extensive neuropsychological and clinical assessment. Lipoprotein levels were measured via 1H NMR from native serum samples. Results: Serum cholesterol and many primarily cholesterol-associated lipoprotein measures clearly decreased in MCI while the trends were increasing for those elderly people who maintained normal cognition. Conclusion: These findings suggest that a decreasing trend in serum cholesterol measures in elderly individuals may suffice as an indication for more detailed inspection for potential signs of cognitive decline.
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| 3. |
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| 4. |
- Paajanen, T, et al.
(författare)
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CERAD Neuropsychological Total Scores Reflect Cortical Thinning in Prodromal Alzheimer's Disease
- 2013
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 3:1, s. 446-58
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Sensitive cognitive global scores are beneficial in screening and monitoring for prodromal Alzheimer's disease (AD). Early cortical changes provide a novel opportunity for validating established cognitive total scores against the biological disease markers. <b><i>Methods:</i></b> We examined how two different total scores of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and the Mini-Mental State Examination (MMSE) are associated with cortical thickness (CTH) in mild cognitive impairment (MCI) and prodromal AD. Cognitive and magnetic resonance imaging (MRI) data of 22 progressive MCI, 78 stable MCI, and 98 control subjects, and MRI data of 103 AD patients of the prospective multicenter study were analyzed. <b><i>Results:</i></b> CERAD total scores correlated with mean CTH more strongly (r = 0.34-0.38, p < 0.001) than did MMSE (r = 0.19, p = 0.01). Of those vertex clusters that showed thinning in progressive MCI, 60-75% related to the CERAD total scores and 3% to the MMSE. <b><i>Conclusion:</i></b> CERAD total scores are sensitive to the CTH signature of prodromal AD, which supports their biological validity in detecting early disease-related cognitive changes.
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| 5. |
- Spulber, Gabriela, et al.
(författare)
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Whole brain atrophy rate predicts progression from MCI to Alzheimer's disease
- 2010
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 31:9, s. 1601-1605
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Tidskriftsartikel (refereegranskat)abstract
- For both clinical and research reasons, it is essential to identify which mild cognitive impairment (MCI) subjects subsequently progress to Alzheimer's disease (AD). The prediction may be facilitated by accelerated whole brain atrophy exhibited by AD subjects. Iterative principal component analysis (IPCA) was used to characterize whole brain atrophy rates using sequential MRI scans for 102 MCI subjects from the Kuopio University Hospital. We modelled the likelihood of progression to probable AD, and found that each additional percent of annualized whole brain atrophy rate was associated with a higher odds ratio (OR) of progression (OR=1.30, p=0.01, 95% CI=1.05-1.60). Our study demonstrates an association between whole brain atrophy rate and subsequent rate of clinical progression from MCI to AD. These findings suggest that IPCA could be an effective brain-imaging marker of progression to AD and useful tool for the evaluation of disease-modifying treatments.
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| 6. |
- Hallikainen, J, et al.
(författare)
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Emergency medical services in rural areas of Finland
- 2014
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Ingår i: NOTFALL & RETTUNGSMEDIZIN. - : Springer Science and Business Media LLC. - 1434-6222 .- 1436-0578. ; 17:3, s. 199-201
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Hartikainen, Päivi, et al.
(författare)
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Cortical thickness in frontotemporal dementia, mild cognitive impairment, and Alzheimer's disease
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 30:4, s. 857-874
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness analysis has been proposed as a potential diagnostic measure in memory disorders. In this retrospective study, we compared the cortical thickness values of 24 patients with frontotemporal dementia (FTD) to those of 25 healthy controls, 45 symptomatic subjects with stable mild cognitive impairment (S-MCI), 15 subjects with progressive mild cognitive impairment (P-MCI), and 36 patients with Alzheimer's disease (AD). The patterns of regions of thinning in FTD when compared to controls and also S-MCI patients showed similar trends; thinning of the bilateral frontal poles and bilateral medial temporal lobe structures, especially the anterior part of the gingulum, the uncus, and parahippocampal gyri. Cortical thinning in FTD was also found on the boundary regions of parietal and occipital lobes. In the P-MCI group compared to FTD, the trend of thinning in small distinct areas of the parietal and occipital lobes was observed. The FTD and AD groups did not differ statistically, but we found trends toward thinning in FTD of the left cingulate gyrus, and the left occipitotemporal gyri, and in AD of the inferior parietal, occipitoparietal, and the pericalcarine regions, more in the right hemisphere. In FTD, increased slowness in the executive test (Trail-Making A) correlated with the thinner cortex, whereas the language tests showed the lower scores, the thinner cortex in the left hemisphere. Cortical thickness might be a tool for detecting subtle changes in brain atrophy in screening of dementia prior to the development of diffuse or lobar atrophies.
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| 8. |
- Solomon, Alina, et al.
(författare)
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Validity dementia and Alzheimer's disease diagnoses in Finnish national registers
- 2014
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 10:3, s. 303-309
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Tidskriftsartikel (refereegranskat)abstract
- Background: We investigated dementia and Alzheimer disease (AD) diagnoses in three national registers in Finland: the Hospital Discharge Register (HDR), the Drug Reimbursement Register, and the Causes of Death Register (CDR). Methods: The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study was used as the gold standard. Participants were first evaluated in 1972 to 1987, and were reexamined in 1998 and in 2005 to 2008. Results: Two approaches were used for the HDR: with a time restriction (considering positive only those cases recorded in the HDR before CAIDE study evaluations) and without a time restriction. Sensitivity of the HDR was 13.7% with time restriction and 51% without time restriction (dementia), and 15.6% with time restriction 55.6% without time restriction (AD). The positive predictive value (PPV) was 87.5% with time restriction and 96.3% without time restriction (dementia), and 100% for AD. Sensitivity and PPV of the HDR were greater after 1998. For AD in the Drug Reimbursement Register alone, sensitivity was 63.5% and PPV was 97.1%; together with the HDR, sensitivity became 65.4% with time restriction and 71.1% without time restriction, and PPV was 100%. For dementia in the CDR, sensitivity was 62.2% and PPV was 100%. Conclusions: Diagnoses in registers have very good accuracy, but underestimation of dementia/AD occurrence may cause an underestimation of associations with risk/protective factors.
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