| 61. |
- Kovacs, Gabor G., et al.
(författare)
-
Mixed brain pathologies in dementia : the BrainNet Europe consortium experience
- 2008
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 26:4, s. 343-350
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dementia results from heterogeneous diseases of the brain. Mixed disease forms are increasingly recognized. METHODS: We performed a survey within brain banks of BrainNet Europe to estimate the proportion of mixed disease forms underlying dementia and age- and gender-specific influences. RESULTS: Data collected in 9 centres from 3,303 individuals were analysed. The proportion of patients with mixed diagnoses among all cases with Alzheimer disease (AD), vascular pathology (VP), argyrophilic grain dementia (AGD), and synucleinopathies, such as Lewy body dementia (LBD), Parkinson disease (PD) and synuclein pathology only in the amygdala, was 53.3%. Mixed pathology was more frequently reported with LBD, PD, AGD, and VP than with AD. The percentage of mixed diagnoses for AGD and VP significantly differed between centres. In patients younger than 75 years, synucleinopathies, and pure forms of AD, VP, and AGD were more frequent in men. Above 75 years of age, more women had pure AD and pure AGD. CONCLUSIONS: The most obvious neuropathological alteration should not terminate the diagnostic procedure since copathology is likely to be found. Neuropathological interpretation of AGD and VP has not been sufficiently established in a consensus. Pure forms of synucleinopathies are unlikely sole substrates for dementia.
|
|
| 62. |
|
|
| 63. |
- Kämäläinen, Anna, et al.
(författare)
-
GRN Variant rs5848 Reduces Plasma and Brain Levels of Granulin in Alzheimer's Disease Patients.
- 2013
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 33:1, s. 23-7
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants in the granulin (GRN) gene have been shown to increase the risk of Alzheimer's disease (AD). Here, we report that the A allele of rs5848 in GRN reduces plasma granulin levels in a dose-dependent manner in a clinically-defined AD sample cohort. Similarly, the mRNA levels of granulin were decreased with respect to A allele of rs5848 in the inferior temporal cortex of neuropathologically confirmed AD patients. Our findings suggest that the A allele of rs5848 is functionally relevant by reducing the expression of granulin.
|
|
| 64. |
- Laitera, Tiina, et al.
(författare)
-
Increased gamma-Secretase Activity in Idiopathic Normal Pressure Hydrocephalus Patients with beta-Amyloid Pathology
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93717-
-
Tidskriftsartikel (refereegranskat)abstract
- The potential similarity between the brain pathology of idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer disease (AD) is intriguing and thus further studies focusing on the underlying molecular mechanisms may offer valuable information for differential diagnostics and the development of treatments for iNPH. Here, we investigated beta- and gamma-secretase activities in relation to amyloid-beta (A beta) pathology in the brain tissue samples collected from iNPH and AD patients. beta- and gamma-secretase activities were measured from the frontal cortical biopsies of 26 patients with suspected iNPH as well as post-mortem tissue samples from the inferior temporal cortex of 74 AD patients and eight subjects without neurofibrillary pathology. In iNPH samples with detectable A beta plaques, gamma-secretase activity was significantly increased (similar to 1.6-fold) when compared to iNPH samples without A beta plaques (p=0.009). In the AD samples, statistically significant differences in the gamma-secretase activity were not observed with respect to disease severity (mild, moderate and severe AD according to neurofibrillary pathology). Conversely, beta-secretase activity was unaltered in iNPH samples with or without A beta plaques, while it was significantly increased in relation to disease severity in the AD patients. These results show for the first time increased gamma-secretase but not b-secretase activity in the biopsy samples from the frontal cortex of iNPH patients with AD-like A beta pathology. Conversely, the opposite was observed in these secretase activities in AD patients with respect to neurofibrillary pathology. Despite the resemblances in the A beta pathology, iNPH and AD patients appear to have marked differences in the cellular mechanisms responsible for the production of A beta.
|
|
| 65. |
- Laitera, Tiina, et al.
(författare)
-
The Expression of Transthyretin and Amyloid-beta Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients
- 2015
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 48:4, s. 959-968
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition in which Alzheimer's disease (AD)related amyloid-beta (A beta) plaques are frequently observed in the neocortex. iNPH patients with prominent A beta pathology show AD-related alterations in amyloid-beta protein precursor (A beta PP) processing resulting from increased gamma-secretase activity. Objectives: Our goal was to assess potential alterations in the global gene expression profile in the brain of iNPH patients as compared to non-demented controls and to evaluate the levels of the identified targets in the cerebrospinal fluid (CSF) of iNPH patients. Methods: The genome-wide expression profile of similar to 35,000 probes was assessed in the RNA samples obtained from 22 iNPH patients and eight non-demented control subjects using a microarray chip. The soluble levels of sA beta PP alpha, sA beta PP beta, and transthyretin (TTR) were measured from the CSF of 102 iNPH patients using ELISA. Results: After correcting the results for multiple testing, significant differences in the expression of TTR and A beta PP were observed between iNPH and control subjects. The mRNA levels of TTR were on average 17-fold lower in iNPH samples compared to control samples. Conversely, the expression level of A beta PP was on average three times higher in iNPH samples as compared to control samples. Interestingly, the expression of beta-secretase (ADAM10) was also increased in iNPH patients. In the lumbar CSF samples, soluble TTR levels showed a significant positive correlation with sA beta PP alpha and sA beta PP beta, but TTR levels did not predict the brain pathology or the shunt response. Conclusions: These findings suggest differences in the expression profile of key factors involved in AD-related cellular events in the brain of iNPH patients.
|
|
| 66. |
- Laiterä, Tiina, et al.
(författare)
-
Effects of Alzheimer's Disease-Associated Risk Loci on Amyloid-β Accumulation in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients
- 2017
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 55:3, s. 995-1003
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition featuring characteristic symptoms, ventriculomegaly, and normal or slightly elevated cerebrospinal fluid pressure. In Alzheimer's disease (AD) patients, diffuse aggregates of amyloid-β (Aβ) and neurofibrillary hyperphosphorylated tau are detected in the neocortex of the brain, while similar accumulation of Aβ is also detected in iNPH. Recent genome-wide association studies have identified several novel risk loci for AD, potentially affecting Aβ-related cellular processes. Apart from the apolipoprotein E ɛ4 allele (APOE4), the risk effect of single loci is low, emphasizing the importance of the polygenic risk score approach when assessing the combined effects.OBJECTIVE: To study the effects of AD-associated individual and polygenic risk score of single nucleotide polymorphisms (SNPs) on the accumulation of Aβ in the brain samples of iNPH patients.METHODS: A sample set of frontal cortex biopsies from 188 iNPH patients were divided into two groups according to the Aβ pathology. After the genotyping of the AD-associated risk loci, polygenic risk score was calculated for each iNPH patient and subsequently analyzed in relation to Aβ deposition.RESULTS: Apart from the APOE4, none of the SNPs revealed a statistically significant effect on the accumulation of Aβ in iNPH. Also, the non-APOE4 polygenic risk score did not associate with Aβ deposition.CONCLUSION: Novel AD-associated risk genes have no significant effect on Aβ accumulation in the brain of iNPH patients. However, APOE4 affects the Aβ deposition in the brain of iNPH and AD patients in a similar manner.
|
|
| 67. |
|
|
| 68. |
- Lambert, Jean-Charles, et al.
(författare)
-
The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease : a Meta-Analysis Study
- 2010
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 22:1, s. 247-255
-
Tidskriftsartikel (refereegranskat)abstract
- The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
|
|
| 69. |
- Lehtisalo, Jenni, et al.
(författare)
-
Dietary changes and cognition over 2 years within a multidomain intervention trial-The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)
- 2019
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:3, s. 410-417
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Association between healthy diet and better cognition is well established, but evidence is limited to evaluate the effect of dietary changes adopted in older age.Methods: We investigated the role of dietary changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) with 1260 at-risk participants (60-77 years) who were randomized to intensive multidomain intervention (including dietary counseling) or regular health advice for 2 years. Parallel process latent growth curves of adherence to dietary recommendations and cognitive performance were analyzed.Results: Adherence to healthy diet at baseline predicted improvement in global cognition, regardless of intervention allocation (P = .003). Dietary improvement was associated with beneficial changes in executive function, especially in the intervention group (P = .008; P = .051 for groups combined).Discussion: Dietary changes initiated during the intervention were related to changes in executive function in 2 years. Long-term diet appeared more influential for global cognition.
|
|
| 70. |
- Lehtisalo, Jenni, et al.
(författare)
-
Nutrient intake and dietary changes during a 2-year multi-domain lifestyle intervention among older adults : secondary analysis of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomised controlled trial
- 2017
-
Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 118:4, s. 291-302
-
Tidskriftsartikel (refereegranskat)abstract
- Advancing age increases the risk for diseases and health concerns like cognitive decline, constituting a major public health challenge. Lifestyle, especially healthy diet, affects many risk factors related to chronic diseases, and thus lifestyle interventions among older adults may be beneficial in promoting successful ageing. We completed a randomised 2-year multi-domain lifestyle intervention trial aiming at prevention of cognitive decline among 631 participants in the intervention and 629 in the control group, aged 60-77 years at baseline. Dietary counselling was one of the intervention domains together with strength exercise, cognitive training and management of CVD risk factors. The aim of this paper was to describe success of the intervention -that is, how an intervention based on national dietary recommendations affected dietary habits as a part of multi-intervention. Composite dietary intervention adherence score comprising nine distinct goals (range 0-9 points from none to achieving all goals) was 5.0 at baseline, and increased in the intervention group after the 1st (P< 0.001) and 2nd (P = 0.005) year. The difference in change compared with the control group was significant at both years (P < 0.001 and P= 0.018). Intake of several vitamins and minerals decreased in the control group but remained unchanged or increased in the intervention group during the 2 years. Well-targeted dietary counselling may prevent age-related decline in diet quality and help in preventing cognitive decline.
|
|
