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- Annerbo, S, et al.
(author)
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The relation between homocysteine levels and development of Alzheimer's disease in mild cognitive impairment patients
- 2005
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 20:4, s. 209-214
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate over a 3-year period the connection between homocysteine (Hcy) levels and development of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI). Hcy was analyzed in 68 men, mean age 65 years, and 68 women, mean age 64 years. Age, sex, cobalamin, folate, creatinine, and thyroid profiles as well as results of Mini-Mental State Examination at the first visit to the memory investigation unit of a geriatric department were recorded from patient journals collected between 1992 and 1999. The total numbers of persons who converted to AD within a period of 3 years from initial investigation with baseline Hcy sampling was 12 of 46 (26%) males, and 18 of 50 women (36%). The total percentage of men and women converting to AD was 31%. Thirty-three percent of men with Hcy levels >20 µmol/l converted to AD. The corresponding figure for men with Hcy levels 20–17 µmol/l was 50%, whereas none of the 18 men with Hcy levels <17 µmol/l converted to AD. These differences were statistically significant. There was also a statistically significant difference between the percentage of women with Hcy levels >16 µmol/l who converted to AD (45%) as compared to those with Hcy levels <16 µmol/l who converted (21%). These findings are inconsistent with the results of other studies showing a positive correlation with hyperhomocysteinemia and occurrence of AD. However, our findings tentatively suggest a possible protective effect of low/normal Hcy levels on dementia conversion in MCI patients.
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| 19. |
- Annerbo, S, et al.
(author)
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The significance of thyroid-stimulating hormone and homocysteine in the development of Alzheimer's disease in mild cognitive impairment: a 6-year follow-up study
- 2006
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In: American journal of Alzheimer's disease and other dementias. - : SAGE Publications. - 1533-3175 .- 1938-2731. ; 21:3, s. 182-8
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Journal article (peer-reviewed)abstract
- Mild cognitive impairment (MCI) represents a transition between normal aging and Alzheimer’s disease (AD). The aim of this study was to investigate the predictive value of vitamin B12/folate, homocysteine, standard laboratory parameters, and concomitant diseases for development of AD in persons with an MCI diagnosis. Development of dementia was followed for 6 years in 93 consecutively recruited MCI persons. Information concerning the above factors was obtained from medical journals. Thirty-four percent of participants converted to AD within 6 years. A forward stepwise logistic regression was performed. The odds ratio (OR) for the Mini-Mental State Examination (MMSE) was 0.777; for age, 1.084; and for thyroid stimulating hormone (TSH), 0.287. The OR for homocysteine was 1.287 at 60 years of age and 1.087 at 65 years of age. Lower TSH levels together with the more established factors lower MMSE, higher homocysteine levels, and age were found to be predictive factors of AD. This may have clinical implications with regard to monitoring TSH levels and thyroxin substitution in MCI patients.
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- Blomberg, M, et al.
(author)
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Cerebrospinal fluid tau levels increase with age in healthy individuals
- 2001
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:2, s. 127-132
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45–80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.
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- Bronge, L, et al.
(author)
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Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study
- 2002
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 13:4, s. 205-212
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Journal article (peer-reviewed)abstract
- To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer’s disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r<sup>2</sup> = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.
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- Bronge, L, et al.
(author)
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White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype
- 1999
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:2, s. 89-96
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Journal article (peer-reviewed)abstract
- To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer’s disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype σ4/4 had more extensive WMLs in the deep white matter than patients with genotypes σ3/3 and σ3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE σ3/3 genotype. In patients carrying at least one σ4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele σ4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.
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| 40. |
- Bronge, L, et al.
(author)
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White matter lesions in dementia: an MRI study on blood-brain barrier dysfunction
- 2000
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 11:5, s. 263-267
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Journal article (peer-reviewed)abstract
- White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common in dementia. Both conditions may be a consequence of small-vessel disease, in which case the BBB damage would be suspected to be located to the WMLs. To further evaluate the nature of WMLs in dementia we examined 10 demented patients with WMLs, including 5 cases with elevated CSF/serum albumin ratios as an indication of BBB damage. An optimised gadolinium (Gd)-enhanced MRI technique was used including a double dose of Gd, a 30-min scan time after injection and analysis of the MR signal in the WMLs as a function over time. Results showed no significant changes in MR signal in the WMLs after contrast administration. We conclude that WMLs are not connected to BBB damage to such a degree that is detectable with this method and that the elevated CSF albumin might have another origin.
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- Cavallin, L, et al.
(author)
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Can dynamic susceptibility contrast magnetic resonance imaging replace single-photon emission computed tomography in the diagnosis of patients with Alzheimer's disease? A pilot study
- 2006
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In: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:9, s. 977-985
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Journal article (peer-reviewed)abstract
- Purpose: To compare single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer's disease (AD). Material and Methods: Twenty-four patients, eight with AD, 10 with MCI, and six controls were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with gadobutrol. Three observers performed a visual interpretation of the SPECT and MR images using a four-point visual scale. Results: SPECT was superior to DSC-MRI in differentiating normal from pathological. All three observers showed statistically significant results in discriminating between the control group, AD, and MCI by SPECT, with a P value of 0.0006, 0.04, and 0.01 for each observer. The statistical results were not significant for MR ( P values 0.8, 0.1, and 0.2, respectively). Conclusion: DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer's disease. Several patient- and method-related improvements should be made before this method can be recommended for clinical practice.
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| 44. |
- Cavallin, L, et al.
(author)
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Overtime reliability of medial temporal lobe atrophy rating in a clinical setting
- 2012
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In: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 53:3, s. 318-323
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Journal article (peer-reviewed)abstract
- Medial temporal lobe atrophy (MTA) is one of the first magnetic resonance imaging (MRI) signs in patients with Alzheimer's disease (AD) and used as a measure of disease progression. Visual assessment of MTA is easy to perform but the reliability of MTA rating over time has not been studied. Purpose To investigate what happens to the MTA rating scores if two radiologists rate the same MRI scans six times over a period of 1 year. Material and Methods One hundred outpatients were included in this study. All patients underwent MRI with a protocol and sequences used for geriatric patients, according to local clinical standards. One neuroradiologist and one general radiologist independently of each other performed retrospective visual assessments of MTA six times, using the same scans, over a period of 1 year. Results Intra-rater kappa varied between κ 0.65 and 0.84 for the neuroradiologist and κ 0.38 and 0.74 for the general radiologist. Intra-rater weighted kappa (wκ) values showed almost perfect agreement for both investigators (wκ 0.83–0.94). Inter-rater reliability showed fair to moderate agreement, with the kappa value varying from κ 0.29 to 0.48 and weighted kappa values ranging from wκ 0.72 to 0.84. There was a statistically significant difference in rating between the two investigators. Conclusion Visual assessment of MTA repeated over time has a high grade of reproducibility when performed by an experienced investigator. The reproducibility drops when assessment is rarely performed. Inter-rater reliability is low when two investigators not working together are compared.
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| 45. |
- Cavallin, L, et al.
(author)
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Voxel-based correlation between coregistered single-photon emission computed tomography and dynamic susceptibility contrast magnetic resonance imaging in subjects with suspected Alzheimer disease
- 2008
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In: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:10, s. 1154-1161
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Journal article (peer-reviewed)abstract
- Background: Current diagnosis of Alzheimer disease is made by clinical, neuropsychologic, and neuroimaging assessments. Neuroimaging techniques such as magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) could be valuable in the differential diagnosis of Alzheimer disease, as well as in assessing prognosis. Purpose: To compare SPECT and MRI in a cohort of patients examined for suspected dementia, including patients with no objective cognitive impairment (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). Material and Methods: 24 patients, eight with AD, 10 with MCI, and six controls, were investigated with SPECT using 99mTc-hexamethylpropyleneamine oxime (HMPAO, Ceretec; GE Healthcare Ltd., Little Chalsont UK) and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a contrast-enhancing gadobutrol formula (Gadovist; Bayer Schering Pharma, Berlin, Germany). Voxel-based correlation between coregistered SPECT and DSC-MR images was calculated. Region-of-interest (ROI) analyses were then performed in 24 different brain areas using brain registration and analysis of SPECT studies (BRASS; Nuclear Diagnostics AB, Stockholm, Sweden) on both SPECT and DSC-MRI. Results: Voxel-based correlation between coregistered SPECT and DSC-MR showed a high correlation, with a mean correlation coefficient of 0.94. ROI analyses of 24 regions showed significant differences between the control group and AD patients in 10 regions using SPECT and five regions in DSC-MR. Conclusion: SPECT remains superior to DSC-MRI in differentiating normal from pathological perfusion, and DSC-MRI could not replace SPECT in the diagnosis of patients with Alzheimer disease.
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| 47. |
- Cedres, N, et al.
(author)
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Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer's Disease
- 2021
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In: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 20:4, s. 153-164
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer’s Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]). <b><i>Methods:</i></b> A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and <i>APOE</i> genotype. <b><i>Results:</i></b> Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N− profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T−N− or A+T−N+ profiles clustered together and were mainly from KIDS. <i>APOE</i> ε4 carriers more frequently showed the A+T−N− and A+T+N− profiles. <b><i>Conclusions:</i></b> Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.
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