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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Laukka, E J, et al.
(författare)
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The influence of vascular disease on cognitive performance in the preclinical and early phases of Alzheimer's disease
- 2010
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : Karger. - 1420-8008 .- 1421-9824. ; 29:6, s. 498-503
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: Alzheimer's disease (AD) is one of the most important causes of old-age cognitive impairment. We aimed to examine the influence of history of vascular disease on cognition in preclinical and early AD.METHODS: Participants from a population-based study were assessed twice with a test of global cognition. The study sample was nondemented at baseline. Three years later, 138 persons were diagnosed with AD and 783 persons remained nondemented. History of vascular disease (heart disease, cerebrovascular disease) was assessed at both occasions.RESULTS: Analyses of covariance revealed significant main effects of group (AD; comparison group) and vascular disease (present; absent) at baseline and follow-up (p < 0.01). At follow-up, a significant interaction indicated that the AD group was more negatively affected by vascular disease (p < 0.01). The fastest rate of cognitive decline was observed for those persons with preclinical AD who had new recordings of vascular disease.CONCLUSIONS: History of vascular disease has a negative impact on cognition in old age. This effect is most pronounced in persons in the earliest clinical phases of AD. Treatment of vascular risk factors in early AD might postpone time of diagnosis and slow down dementia progression.
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- Leitman, David I., et al.
(författare)
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Not pitch perfect : Sensory contributions to affective communication impairment in schizophrenia
- 2011
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 70:7, s. 611-618
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Tidskriftsartikel (refereegranskat)abstract
- Background: Schizophrenia patients have vocal affect (prosody) deficits that are treatment resistant and associated with negativesymptoms and poor outcome. The neural correlates of this dysfunction are unclear. Prior study has suggested that schizophrenia vocal affectperception deficits stem from an inability to use acoustic cues, notably pitch, in decoding emotion. Methods: Functional magnetic resonance imaging was performed in 24 schizophrenia patients and 28 healthy control subjects, during theperformance of a four-choice (happiness, fear, anger, neutral) vocal affect identification task in which items for each emotion variedparametrically in affective salient acoustic cue levels. Results: We observed that parametric increases in cue levels in schizophrenia failed to produce the same identification rate increases as incontrol subjects. These deficits correlated with diminished reciprocal activation changes in superior temporal and inferior frontal gyri andreduced temporo-frontal connectivity. Task activation also correlated with independent measures of pitch perception and negativesymptom severity. Conclusions: These findings illustrate the interplay between sensory and higher-order cognitive dysfunction in schizophrenia. Sensorycontributions to vocal affect deficits also suggest that this neurobehavioral marker could be targeted by pharmacological or behavioralremediation of acoustic feature discrimination.
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- Speh, Andreja, et al.
(författare)
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The Relationship Between Cardiovascular Health and Rate of Cognitive Decline in Young-Old and Old-Old Adults : A Population-Based Study
- 2021
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 84:4, s. 1523-1537
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Tidskriftsartikel (refereegranskat)abstract
- Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. Methods: This cohort study included 1,950 participants aged >= 60 years (M= 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (beta=0.21, 95% CI 0.12-0.29), verbal fluency (beta=0.08, 0.00-0.16), and global cognition (beta = 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals. Conclusion: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.
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