| 1. |
- Chwiszczuk, L, et al.
(författare)
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Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease
- 2016
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 16:3-4, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Sleep disturbances (SDs) are common in patients with all forms of dementia. However, most studies focus on Alzheimer's disease (AD) and less is known about the prevalence and characteristics of SD in dementia with Lewy bodies (DLB). <b><i>Objective:</i></b> The aims of this cross-sectional study were: (1) to examine the frequency of SD in DLB versus AD; (2) to compare patients with and without SD with regard to relevant clinical variables, and (3) to investigate the associations between SD and medication use. <b><i>Methods:</i></b> Patients with a first-time diagnosis of probable or possible DLB or AD were selected from the Dementia Study of Western Norway and recruited from clinics for old age psychiatry from 2010 until the end of 2013. <b><i>Results:</i></b> In all, 123 (55.7%) subjects with dementia suffered from at least one SD. Insomnia was present in 77 (34.8%), and 34 (20.7%) patients had probable REM-sleep behaviour disorder (RBD). All SDs were also significantly more frequent in patients with DLB than in AD, and DLB patients also more often had several co-occurring SDs. The presence of any SD was associated with more neuropsychiatric symptoms, higher morbidity, more parkinsonian symptoms and excessive daytime sleepiness. Antiparkinsonian medication was used more often in RBD, restless leg syndrome (RLS) and periodic limb movements, and benzodiazepines were also common in RLS. <b><i>Conclusions:</i></b> Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB.
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| 2. |
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| 3. |
- Gallo, Valentina, et al.
(författare)
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Parkinson's Disease Case Ascertainment in the EPIC Cohort : The NeuroEPIC4PD Study
- 2015
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 15:6, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. Results: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. Conclusions: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies.
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| 4. |
- Haller, Sven, et al.
(författare)
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Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects
- 2019
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Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 19:3-4, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions.METHODS: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL.RESULTS: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele.CONCLUSION: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.
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| 5. |
- Orellana, C, et al.
(författare)
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Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations
- 2016
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 16:1-2, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. <b><i>Summary:</i></b> The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. <b><i>Key Messages:</i></b> The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.
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| 6. |
- Pinto, Susana, et al.
(författare)
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Health Status Perspectives in Amyotrophic Lateral Sclerosis
- 2017
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 17:6, s. 323-329
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The global perception of the health status (HS) of amyotrophic lateral sclerosis (ALS) patients before the initial diagnosis has not been addressed previously. Methods: We recorded the following at the first visit, before diagnostic information: (1) visual analog scale (VAS) of the EQ-5D; (2) the revised ALS functional rating scale (ALSFRSR), bulbar (ALSFRSb), upper limb (ALSFRSul), lower limb (ALSFRSll), and respiratory (RofALSFRS-R) subscores; and (3) forced and slow vital capacities. Correlations were tested by the Pearson correlation test. Variables were compared between groups defined by the VAS median value. p < 0.05 was considered significant. Results: Of the 156 patients included in the study (91 spinal-onset, 49 bulbar-onset, 16 axial/respiratory- onset; 95 men; mean onset age 63.9 +/- 13 years; mean disease duration 18.4 +/- 26.5 months), HS VAS was significantly lower in spinal-onset patients (p = 0.047), and particularly in spinal-onset women (p = 0.027). Disease duration had no influence. HS VAS was moderately correlated with ALS-FRS, ALSFRSul and ALSFRSll (0.4 < r < 0.5, p < 0.01), weakly correlated with RofALSFRS-R in the whole population (r = 0.171, p < 0.05), and not correlated with ALSFRSb or the respiratory tests. ALSFRSb was similar between groups defined by the HS VAS median value, but the other scores were significantly lower for poorer HS values. Conclusion: HS before diagnosis is mostly dependent on the perception of upper and lower limb function. A tool tailored to evaluate HS in bulbar-onset patients should be developed.
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| 7. |
- Portelius, Erik, 1977, et al.
(författare)
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Brain Amyloid-Beta Fragment Signatures in Pathological Ageing and Alzheimer's Disease by Hybrid Immunoprecipitation Mass Spectrometry
- 2015
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Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 15:1, s. 50-57
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Tidskriftsartikel (refereegranskat)abstract
- Background: Senile plaques in Alzheimer's disease (AD) are composed of amyloid-beta (A beta) especially N-truncated forms including A beta(4-42). These are thought to be neurotoxic. However, individuals may live for decades with biomarker evidence of cerebral beta-amyloidosis (positive amyloid PET imaging and/or low cerebrospinal fluid levels of the 42 amino acid form of A beta) without cognitive impairment. This condition may be termed pathological ageing (PA). Objective: To investigate whether there is a difference in the cerebral A beta fragment pattern in brain specimens from non-demented (PA) and demented (AD) individuals expressing the full neuropathological triad of AD (senile plaques, neurofibrillary tangles and neurodegeneration). Methods: We extracted A beta using formic acid and hybrid (6E10 and 4G8) immunoprecipitation from fresh-frozen temporal cortex tissue of 6 elderly individuals (mean age +/- SD:89 +/- 3.5 years) with PA and 10 patients with AD (mean age +/- SD: 72 +/- 8.5 years). The full spectrum of A beta peptides was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results: AD patients had generally more N-terminally truncated and pyroglutamate-modified A beta than PA patients, whereas PA patients had on average more A beta(1-40) than AD patients. Conclusion: Senile plaques in AD may have an AB fragment composition distinct from PA with more N-terminally and pyroglutamate-modified A beta peptides that may be linked to neurotoxicity. (C) 2015 S. Karger AG, Basel
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| 8. |
- Tsolaki, Anthoula C., et al.
(författare)
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Prevalence of Apolipoprotein E Polymorphisms in Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Elderly : A Northern Greece Study
- 2018
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Ingår i: Neurodegenerative Diseases. - : S. Karger. - 1660-2854 .- 1660-2862. ; 18:4, s. 216-224
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Tidskriftsartikel (refereegranskat)abstract
- Background: Apolipoprotein E epsilon 4 allele (APOE epsilon 4) is a major genetic risk factor for Alzheimer's disease (AD). APOE epsilon 4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of epsilon 4/4 homozygotes were 1.9, 1.6, and 5.7%, while the epsilon 4/- carriers' distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of epsilon 4/4 for AD was 5.731-fold higher compared to the estimated odds of epsilon 3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE epsilon 4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE epsilon 4 genotype have nearly the same odds of developing MCI and AD.
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| 9. |
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| 10. |
- Xu, SH, et al.
(författare)
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Overexpression of SNX3 Decreases Amyloid-β Peptide Production by Reducing Internalization of Amyloid Precursor Protein
- 2018
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Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 18:1, s. 26-37
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Sorting nexins (SNXs) have diverse functions in protein sorting and membrane trafficking. Recently, single-nucleotide polymorphisms in SNX3 were found to be associated with Alzheimer disease. However, it remains unknown whether SNX3 participates in amyloid (A)β peptide production. <b><i>Objective:</i></b> To examine the role of SNX3 in Aβ production and APP processing. <b><i>Methods:</i></b> The effect of increased expression of SNX3 was studied in HEK293T cells. Aβ peptides were measured by immunoassay. Protein-protein association was analyzed by a bimolecular fluorescence complementation (BiFC) assay. APP uptake was measured with an α-bungarotoxin-binding assay, and flow cytometry was used to measure cell surface APP levels. <b><i>Results:</i></b> We found that overexpression of SNX3 in HEK293T cells decreases the levels of secreted Aβ and soluble N-terminal APP fragments (sAPPβ). The reduction correlated with a decreased association of APP with BACE1, as revealed by BiFC. This effect may, in part, be explained by a reduced internalization of APP; SNX3 overexpression reduced APP internalization as determined by an α-bungarotoxin-binding assay, and caused increased APP levels on the cell surface, as shown by flow cytometry. In addition, SNX3 overexpression increased the cellular levels of full-length APP. <b><i>Conclusion:</i></b> These results provide evidence that SNX3 regulates Aβ production by influencing the internalization of APP.
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