| 1. |
- Ferrari, Raffaele, et al.
(författare)
-
Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
-
Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
|
|
| 2. |
- Levin, Johannes, et al.
(författare)
-
α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
- 2024
-
Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
|
|
| 3. |
- Schofield, Peter R, et al.
(författare)
-
Ethnic density, urbanicity and psychosis risk for migrant groups - A population cohort study
- 2017
-
Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964. ; 190, s. 82-87
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Rates of psychotic disorder are raised for many migrant groups. Understanding the role played by the social context in which they live may help explain why. This study investigates the effect of both neighbourhood ethnic density and urbanicity on the incidence of non-affective psychosis for migrant groups. Method: Population based cohort of all those born 1965 or later followed from their 15th birthday (2,224,464 people) to 1st July 2013 (37,335,812 person years). Neighbourhood exposures were measured at age 15. Results: For all groups incidence of non-affective psychosis was greater in lower ethnic density neighbourhoods. For migrants of African origin there was a 1.94-fold increase (95% CI, 1.17-3.23) comparing lowest and highest density quintiles; with similar effects for migrants from Europe (excluding Scandinavia): incidence rate ratio (IRR) 1.99 (95% CI, 1.56-2.54); Asia: IRR 1.63 (95% CI, 1.02-2.59); and the Middle East: IRR 1.68 (95% CI, 1.19-2.38). This initial analysis found no evidence for an urbanicity effect for migrant groups. Adjusting for ethnic density revealed a positive association between level of urbanicity and psychosis for two groups, with a statistically significant linear trend (average effect of a one quintile increase) for migrants from Europe: IRR 1.09 (95% CI, 1.02-1.16) and the Middle East: IRR 1.12 (95% CI, 1.01-1.23). Conclusions: In this first nationwide population-based study of ethnic density, urbanicity and psychosis we show that lower ethnic density is associated with increased incidence of non-affective psychosis for different migrant groups; masking urban/rural differences in psychosis for some groups.
|
|
| 4. |
- Schofield, Peter R, et al.
(författare)
-
Neighbourhood ethnic density and psychosis - Is there a difference according to generation?
- 2018
-
Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964. ; 195, s. 501-505
-
Tidskriftsartikel (refereegranskat)abstract
- Background: For different migrant groups living in an area with few people from the same ethnic background is associated with increased psychosis incidence (the ethnic density effect). We set out to answer the question: are there generational differences in this effect? Methods: Analysis of a population based cohort (2.2 million) comprising all those born 1st January 1965, or later, living in Denmark on their 15th birthday. This included 90,476 migrants from Africa, Europe (excluding Scandinavia) and the Middle East, with 55% first generation and the rest second-generation migrants. Neighbourhood co-ethnic density was determined at age 15 and we adjusted for age, gender, calendar period, parental psychiatric history and parental income. Results: For first-generation migrants from Africa, there was no statistically significant difference (p = 0.30) in psychosis rates when comparing lowest with highest ethnic density quintiles, whereas the second generation showed a 3.87-fold (95% CI 1.77-8.48) increase. Similarly, for migrants from the Middle East, the first generation showed no evidence of an ethnic density effect (p = 0.94) while the second showed a clear increase in psychosis when comparing lowest with highest quintiles, incidence rate ratio (IRR) 2.43 (95% CI, 1.18-5.00). For European migrants, there was some limited evidence of an effect in the first generation, (IRR) 1.69 (95% CI, 1.19-2.40), with this slightly raised in the second: IRR 1.80 (95% CI, 1.27-2.56). Conclusions: We found strong evidence for an ethnic density effect on psychosis incidence for second-generation migrants but this was either weak or absent for the first generation.
|
|
