| 1. |
- Andreasen, N, et al.
(författare)
-
Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment
- 1999
-
Ingår i: Neuroscience Letters. - 0304-3940. ; 273:1, s. 5-8
-
Tidskriftsartikel (refereegranskat)abstract
- We studied CSF-tau and CSF-Abeta42 in 16 patients with mild cognitive impairment (MCI) who at follow-up investigations 6-27 months later had progressed to Alzheimer's disease (AD) with dementia. For comparison, we studied 15 age-matched healthy individuals. At baseline, 14/16 (88%) of MCI patients had high CSF-tau and/or low CSF-Abeta42 levels. These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD. This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase.
|
|
| 2. |
- Andreasen, N, et al.
(författare)
-
Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample
- 1999
-
Ingår i: Neurology. - 1526-632X. ; 53:7, s. 1488-1488
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.
|
|
| 3. |
- Minthon, Lennart, et al.
(författare)
-
Correlation between clinical characteristics and cerebrospinal fluid neuropeptide Y levels in dementia of the Alzheimer type and frontotemporal dementia
- 1996
-
Ingår i: Alzheimer Disease and Associated Disorders. - 1546-4156. ; 10:4, s. 197-203
-
Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) has been shown to be involved in the control of several neuroendocrine functions. Moreover, in animal models, NPY produces behavioral effects that are similar to those induced by anxiolytics. We studied NPY-like immunoreactivity (NPY-LI) in cerebrospinal fluid (CSF) in two primary degenerative dementias, Alzheimer disease (AD, n = 34) and frontotemporal dementia (FTD, n = 22) and correlated the CSF NPY-LI levels with clinical characteristics, as rated with the Organic Brain Syndrome scale. There were significant correlations between NPY-LI and such clinical items as suspiciousness, anxiousness, restlessness-agitation, and irritability in both AD and FTD. AD patients, but not FTD patients, showed a significant negative correlation between NPY-LI and duration of the disease. Thus, the study found significant correlations between CSF NPY-LI and emotional symptoms and behavior in organic dementia.
|
|
| 4. |
- Minthon, Lennart, et al.
(författare)
-
Long-term effects of tacrine on regional cerebral blood flow changes in Alzheimer's disease
- 1995
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - 1420-8008. ; 6:5, s. 245-251
-
Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a significant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. Clinical outcome: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer's disease may delay the progression of symptoms.
|
|
| 5. |
- Minthon, Lennart, et al.
(författare)
-
Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with severity of disease and clinical signs in Alzheimer's disease and frontotemporal dementia
- 1997
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 8:4, s. 232-239
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD (n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).
|
|
| 6. |
- Minthon, Lennart, et al.
(författare)
-
The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease
- 1997
-
Ingår i: Neuroscience Letters. - 0304-3940. ; 226:1, s. 65-68
-
Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD.
|
|
| 7. |
- Sjogren, M, et al.
(författare)
-
Decreased monoamine metabolites in frontotemporal dementia and Alzheimer's disease
- 1998
-
Ingår i: Neurobiology of Aging. - 1558-1497. ; 19:5, s. 379-384
-
Tidskriftsartikel (refereegranskat)abstract
- The concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (HMPG) in the cerebrospinal fluid (CSF) of patients with clinical frontotemporal dementia (FTD; n = 30), early onset Alzheimer's disease (EAD; n = 33), late onset Alzheimer's disease (LAD, n = 27) and normal controls (n = 31) were determined using HPLC. ANCOVA showed no significant effect of neuroleptic medication, extrapyramidal signs, myoclonia or gender on the CSF levels of the monoamine metabolites. Homovanillic acid was significantly reduced in all diagnostic groups (FTD, p = 0.0002; EAD, p = 0.016; LAD, p = 0.013). 5-Hydroxyindoleacetic acid was significantly reduced in EAD (p = 0.013) and in LAD (p = 0.0014), and HMPG was reduced in LAD only (p = 0.020). HMPG was significantly higher in FTD compared to EAD (p = 0.0005) and LAD (p = 0.0003). CSF-5-HIAA was significantly reduced in patients with antidepressant medication (p = 0.006). ANCOVA within the FTD group showed no significant effect of neuroleptic or antidepressant medication, extrapyramidal signs, myoclonia, gender or FTD subtype on the CSF levels of the monoamine metabolites. The results suggest that CSF-HMPG might differentiate FTD from EAD and LAD, but not from normals.
|
|
