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- Dintica, Christina S., et al.
(författare)
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Impaired olfaction is associated with cognitive decline and neurodegeneration in the brain
- 2019
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 92:7, s. e700-e709
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveWe aimed to examine whether impaired olfaction is associated with cognitive decline and indicators of neurodegeneration in the brain of dementia-free older adults.MethodsWithin the Rush Memory and Aging Project, 380 dementia-free participants (mean age = 78 years) were followed for up to 15 years, and underwent MRI scans. Olfactory function was assessed using the Brief Smell Identification Test (B-SIT) at baseline, and categorized as anosmia (B-SIT <6), hyposmia (B-SIT 6-10 in men and 6-10.25 in women), and normal (B-SIT 10.25-12 in men and 10.5-12 in women). Cognitive function was annually assessed with a battery of 21 tests, from which composite scores were derived. Structural total and regional brain volumes were estimated. Data were analyzed using linear regression and mixed-effects models.ResultsAt study entry, 138 (36.3%) had normal olfactory function, 213 (56.1%) had hyposmia, and 29 (7.6%) had anosmia. In multiadjusted mixed-effects models, hyposmia (beta = -0.03, 95% confidence interval [CI] -0.05 to -0.02) and anosmia (beta = -0.13, 95% CI -0.16 to -0.09) were associated with faster rate of cognitive decline compared to normal olfaction. On MRI, impaired olfaction (hyposmia or anosmia) was related to smaller volumes of the hippocampus (beta = -0.19, 95% CI -0.33 to -0.05), and in the entorhinal (beta = -0.16, 95% CI -0.24 to -0.08), fusiform (beta = -0.45, 95% CI -0.78 to -0.14), and middle temporal (beta = -0.38, 95% CI -0.72 to -0.01) cortices.ConclusionImpaired olfaction predicts faster cognitive decline and might indicate neurodegeneration in the brain among dementia-free older adults.
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| 2. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 3. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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