| 1. |
- Liu, Yawu, et al.
(författare)
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Diffusion tensor imaging and tract-based spatial statistics in Alzheimer's disease and mild cognitive impairment
- 2011
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Ingår i: Neurobiology of Aging. - Fayetteville, N.Y. : Ankho International. - 0197-4580 .- 1558-1497. ; 32:9, s. 1558-1571
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to explore the changes in fractional anisotropy (FA) in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by analyzing diffusion tensor imaging (DTI) data using the Tract-Based Spatial Statistics (TBSS). DTI data were collected from 17 AD patients, 27 MCI subjects and 19 healthy controls. Voxel-based analysis with TBSS was used to compare FA among the three groups. Additionally, guided by TBSS findings, a region of interest (ROI)-based analysis along the TBSS skeleton was performed on group-level and the accuracy of the method was assessed by the back-projection of ROIs to the native space FA. Neurofiber tracts with decreased FA included: the parahippocampal white matter, cingulum, uncinate fasciculus, inferior and superior longitudinal fasciculus, corpus callosum, fornix, tracts in brain stem, and cerebellar tracts. Quantitative ROI-analysis further demonstrated the significant decrease on FA values in AD patients relative to controls whereas FA values of MCI patients were found in between the controls and AD patients. We conclude that TBSS is a promising method in examining the degeneration of neurofiber tracts in MCI and AD patients.
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| 2. |
- 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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| 3. |
- Julkunen, Valtteri, et al.
(författare)
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Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer's disease patients : a longitudinal study
- 2010
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 21:4, s. 1141-1151
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype.
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| 4. |
- Jönsson, Linus, et al.
(författare)
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Determinants of costs of care for patients with Alzheimer's disease
- 2006
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 21:5, s. 449-459
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, is a major cause of disability and care burden in the elderly. This study aims to estimate the costs of formal and informal care and identity determinants of care costs. MATERIALS AND METHODS: Two hundred and seventy-two (AD) patients and their caregivers were recruited among patients attending regular visits at six memory clinic in Sweden, Denmark, Norway and Finland. Patients with a diagnosis of AD and with an identifiable primary caregiver were eligible for inclusion. Data was collected by questionnaires at baseline, and at scheduled follow-up visits after 6 months and again after 12 months. Cognitive function was assessed with the Mini Mental State Examination (MMSE) and behavioural disturbances were measured using a brief version of the neuropsychiatric inventory (NPI). RESULTS: Total annual costs were on average 172,000 SEK, ranging from 60,700 SEK in mild dementia to 375,000 SEK in severe dementia. Costs for community care (special accommodation, home help, etc.) constituted about half of total costs of care and increase sharply with increasing cognitive impairment. Informal care costs, valued at the opportunity cost of the caregiver's time, make up about a third of total costs and also increased significantly with disease severity. Medical care costs (inpatient care, outpatient care, pharmaceuticals), on the other hand, were not significantly related to disease severity. Regression analysis confirmed a strong association between costs and cognitive function, between patients as well as within patients over time. There was also a significant influence on costs from behavioural disturbances. Sensitivity analysis showed that the method chosen to value informal care can have considerable impact on results. CONCLUSIONS: Costs of care in patient with AD are high and related to dementia severity as well as presence of behavioural disturbances. The cost estimates presented have implications for future economic evaluation of treatments for Alzheimer's disease.
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| 5. |
- Jönsson, Linus, et al.
(författare)
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Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL
- 2006
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Ingår i: Alzheimer Disease and Associated Disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341 .- 1546-4156. ; 20:1, s. 49-55
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to compare patient- and proxy-rated utilities and health-related quality of life from individuals in different stages of Alzheimer disease (AD). Two hundred seventy-two patients and their primary caregivers were enrolled in a prospective observational study and underwent three consecutive interviews, 6 months apart. Average Mini-Mental State Examination (MMSE) scores were 19.3, 18.0, and 16.4 at the three interviews; scores ranged from 0 to 30. Using the EuroQoL EQ-5D instrument, patient-rated health utilities were on average 0.833 with little variation across MMSE-based severity levels. Proxy-rated health utilities were 0.69 (MMSE >25), 0.64 (MMSE 21-25), 0.50 (MMSE 15-20), 0.49 (MMSE 10-14), and 0.33 (MMSE <10). Proxy-rated utilities, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on a brief version of the neuropsychiatric inventory (NPI) and institutionalization. Utilities were highly correlated with the disease-specific quality of life instrument QoL-AD. The study shows that the EuroQoL can be used to rate utilities in Alzheimer disease, but there are important differences between patient- and proxy-ratings.
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| 6. |
- Munoz-Ruiz, Miguel Angel, et al.
(författare)
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Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease
- 2016
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - : S. Karger AG. - 1664-5464. ; 6:2, s. 313-329
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). Methods: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results: The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases (AUC = 0.94), differential diagnosis of AD and FTD performs very well. Conclusions: DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD.
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| 7. |
- Niskanen, Eini, et al.
(författare)
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New insights into Alzheimer's disease progression : a combined TMS and structural MRI study
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.
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| 8. |
- Pentikäinen, Heikki, et al.
(författare)
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Cardiorespiratory fitness and brain volumes in men and women in the FINGER study
- 2017
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 46:2, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- Background: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). Methods: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. Results: in men, VO2peak was associated with cortical GM volume (beta = 0.56, P = 0.001) and total GM volume (beta = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. Conclusion: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.
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| 9. |
- 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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| 10. |
- Spulber, Gabriela, et al.
(författare)
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Evolution of global and local grey matter atrophy on serial MRI scans during the progression from MCI to AD
- 2012
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Ingår i: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 9:4, s. 516-524
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Tidskriftsartikel (refereegranskat)abstract
- Mild cognitive impairment (MCI) often represents a prodromal form of dementia, conferring a significantly higher risk of converting to probable Alzheimer's disease (AD). The aim of this study is to characterise the differences of grey matter (GM) distribution and dynamics between progressive and stable MCI subjects during a 2 year period preceding the conversion to AD. We included 48 stable MCI and 12 progressive MCI cases based on the availability of 3 serial scans acquired with approximately 1 year scan interval. For the progressive MCI group, the third scan was acquired at the time of the clinical diagnosis of AD, while the first two scans were acquired approximately 2 and 1 years earlier. For the stable MCI group, the three scans were acquired at approximately 1 year intervals during a period free from significant cognitive decline. We used longitudinal voxel-based morphometry (VBM) for mapping the progression of GM loss over time. For the progressive MCI group, the cross-sectional analysis revealed areas of lower GM volumes in the parahippocampal gyrus, precuneus and posterior cingulate 12 months before the AD diagnosis. For the longitudinal VBM analysis the progressive MCI group revealed increased GM loss in cortical regions belonging to the temporal neocortex, parahippocampal cortex, and cingulate gyrus. The frontal lobe, insula and the cerebellum were also affected. This accelerated atrophy may offer new insights into the understanding of neurodegenerative pathology and the clinical relevance of these changes remains to be verified by subsequent studies.
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