scholarly journals Alzheimer's Disease Genes Are Associated with Measures of Cognitive Ageing in the Lothian Birth Cohorts of 1921 and 1936

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Gillian Hamilton ◽  
Sarah E. Harris ◽  
Gail Davies ◽  
David C. Liewald ◽  
Albert Tenesa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Phenotypic Variability ◽  
Human Cognition ◽  
Disease Genes ◽  
Birth Cohorts ◽  
Cognitive Ageing ◽  
Cognitive Domains ◽  
Lothian Birth Cohort

Alzheimer's disease patients have deficits in specific cognitive domains, and susceptibility genes for this disease may influence human cognition in nondemented individuals. To evaluate the role of Alzheimer's disease-linked genetic variation on cognition and normal cognitive ageing, we investigated two Scottish cohorts for which assessments in major cognitive domains are available: the Lothian Birth Cohort of 1921 and the Lothian Birth Cohort of 1936, consisting of 505 and 998 individuals, respectively. 158 SNPs from eleven genes were evaluated. Single SNP analyses did not reveal any statistical association after correction for multiple testing. One haplotype fromTRAPPC6Awas associated with nonverbal reasoning in both cohorts and combined data sets. This haplotype explains a small proportion of the phenotypic variability (1.8%). These findings warrant further investigation as biological modifiers of cognitive ageing.

scholarly journals Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80513 ◽  
Author(s):  
Donald M. Lyall ◽  
Natalie A. Royle ◽  
Sarah E. Harris ◽  
Mark E. Bastin ◽  
Susana Muñoz Maniega ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Disease Susceptibility ◽  
Susceptibility Genes ◽  
Lothian Birth Cohort

scholarly journals The genetic and epigenetic profile of serum S100β in the Lothian Birth Cohort 1936 and its relationship to Alzheimer’s disease

2021 ◽  
Vol 6 ◽  
pp. 306
Author(s):  
Danni A Gadd ◽  
Robert I McGeachan ◽  
Robert F Hillary ◽  
Daniel L McCartney ◽  
Sarah E Harris ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Birth Cohort ◽  
Brain Inflammation ◽  
Joint Analysis ◽  
Mendelian Randomisation ◽  
Protein Levels ◽  
S100β Protein ◽  
Lothian Birth Cohort ◽  
Insight Into

Background: Circulating S100 calcium-binding protein (S100β) is a marker of brain inflammation that has been associated with a range of neurological conditions. To provide insight into the molecular regulation of S100β and its potential causal associations with Alzheimer’s disease, we carried out genome- and epigenome-wide association studies (GWAS/EWAS) of serum S100β levels in older adults and performed Mendelian randomisation with Alzheimer’s disease. Methods: GWAS (N=769, mean age 72.5 years, sd = 0.7) and EWAS (N=722, mean age 72.5 years, sd = 0.7) of S100β levels were performed in participants from the Lothian Birth Cohort 1936. Conditional and joint analysis (COJO) was used to identify independent loci. Expression quantitative trait locus (eQTL) analyses were performed for lead loci that had genome-wide significant associations with S100β. Bidirectional, two-sample Mendelian randomisation was used to test for causal associations between S100β and Alzheimer’s disease. Colocalisation between S100β and Alzheimer’s disease GWAS loci was also examined. Results: We identified 154 SNPs from chromosome 21 that associated (P<5x10-8) with S100β protein levels. The lead variant was located in the S100β gene (rs8128872, P=5.0x10-17). We found evidence that two independent causal variants existed for both transcription of S100β and S100β protein levels in our eQTL analyses. No CpG sites were associated with S100β levels at the epigenome-wide significant level (P<3.6x10-8); the lead probe was cg06833709 (P=5.8x10-6), which mapped to the LGI1 gene. There was no evidence of a causal association between S100β levels and Alzheimer’s disease or vice versa and no evidence for colocalisation between S100β and Alzheimer’s disease loci. Conclusions: These data provide insight into the molecular regulators of S100β levels. This context may aid in understanding the role of S100β in brain inflammation and neurological disease.

scholarly journals Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936

2014 ◽  
Vol 35 (6) ◽  
pp. 1513.e25-1513.e33 ◽  
Author(s):  
Donald M. Lyall ◽  
Sarah E. Harris ◽  
Mark E. Bastin ◽  
Susana Muñoz Maniega ◽  
Catherine Murray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Birth Cohort ◽  
Disease Susceptibility ◽  
Susceptibility Genes ◽  
White Matter Integrity ◽  
Brain White Matter ◽  
Lothian Birth Cohort

scholarly journals Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

2021 ◽  
Vol 79 (1) ◽  
pp. 225-235
Author(s):  
Maya Arvidsson Rådestig ◽  
Johan Skoog ◽  
Henrik Zetterberg ◽  
Jürgen Kern ◽  
Anna Zettergren ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cohort Studies ◽  
Cognitive Performance ◽  
Birth Cohort ◽  
Population Based ◽  
Tau Pathology ◽  
Preclinical Alzheimer’S Disease ◽  
Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

2009 ◽  
Vol 15 (6) ◽  
pp. 898-905 ◽  
Author(s):  
AIHONG ZHOU ◽  
JIANPING JIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Domains ◽  
Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

scholarly journals Integrative multi-omics analyses identify cell-type disease genes and regulatory networks across schizophrenia and Alzheimer’s disease

2020 ◽  
Author(s):  
Mufang Ying ◽  
Peter Rehani ◽  
Panagiotis Roussos ◽  
Daifeng Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Disease Genes ◽  
Omics Data ◽  
Cell Type ◽  
Cellular Resolution ◽  
Gene Regulatory

AbstractStrong phenotype-genotype associations have been reported across brain diseases. However, understanding underlying gene regulatory mechanisms remains challenging, especially at the cellular level. To address this, we integrated the multi-omics data at the cellular resolution of the human brain: cell-type chromatin interactions, epigenomics and single cell transcriptomics, and predicted cell-type gene regulatory networks linking transcription factors, distal regulatory elements and target genes (e.g., excitatory and inhibitory neurons, microglia, oligodendrocyte). Using these cell-type networks and disease risk variants, we further identified the cell-type disease genes and regulatory networks for schizophrenia and Alzheimer’s disease. The celltype regulatory elements (e.g., enhancers) in the networks were also found to be potential pleiotropic regulatory loci for a variety of diseases. Further enrichment analyses including gene ontology and KEGG pathways revealed potential novel cross-disease and disease-specific molecular functions, advancing knowledge on the interplays among genetic, transcriptional and epigenetic risks at the cellular resolution between neurodegenerative and neuropsychiatric diseases. Finally, we summarized our computational analyses as a general-purpose pipeline for predicting gene regulatory networks via multi-omics data.

scholarly journals Posterior Cingulate Cortex Network Predicts Alzheimer's Disease Progression

2020 ◽  
Vol 12 ◽  
Author(s):  
Pei-Lin Lee ◽  
Kun-Hsien Chou ◽  
Chih-Ping Chung ◽  
Tzu-Hsien Lai ◽  
Juan Helen Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Large Scale ◽  
Cingulate Cortex ◽  
Posterior Cingulate Cortex ◽  
Cognitive Domains ◽  
Atrophy Rate ◽  
Posterior Cingulate ◽  
Structural Networks

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of toxic misfolded proteins, which are believed to have propagated from disease-specific epicenters through their corresponding large-scale structural networks in the brain. Although previous cross-sectional studies have identified potential AD-associated epicenters and corresponding brain networks, it is unclear whether these networks are associated with disease progression. Hence, this study aims to identify the most vulnerable epicenters and corresponding large-scale structural networks involved in the early stages of AD and to evaluate its associations with multiple cognitive domains using longitudinal study design. Annual neuropsychological and MRI assessments were obtained from 23 patients with AD, 37 patients with amnestic mild cognitive impairment (MCI), and 33 healthy controls (HC) for 3 years. Candidate epicenters were identified as regions with faster decline rate in the gray matter volume (GMV) in patients with MCI who progressed to AD as compared to those regions in patients without progression. These epicenters were then further used as pre-defined regions of interest to map the synchronized degeneration network (SDN) in HCs. Spatial similarity, network preference and clinical association analyses were used to evaluate the specific roles of the identified SDNs. Our results demonstrated that the hippocampus and posterior cingulate cortex (PCC) were the most vulnerable AD-associated epicenters. The corresponding PCC-SDN showed significant spatial association with the patterns of GMV atrophy rate in each patient group and the overlap of these patterns was more evident in the advanced stages of the disease. Furthermore, individuals with a higher GMV atrophy rate of the PCC-SDN also showed faster decline in multiple cognitive domains. In conclusion, our findings suggest the PCC and hippocampus are two vulnerable regions involved early in AD pathophysiology. However, the PCC-SDN, but not hippocampus-SDN, was more closely associated with AD progression. These results may provide insight into the pathophysiology of AD from large-scale network perspective.

Effects of Oral Rivastigmine on Cognitive Domains in Mild-to-Moderate Alzheimer’s Disease

2010 ◽  
Vol 25 (4) ◽  
pp. 347-352 ◽  
Author(s):  
Martin R. Farlow ◽  
Jeffrey L. Cummings ◽  
Jason T. Olin ◽  
Xiangyi Meng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Domains

scholarly journals The utility of questionnaires in cognitive and functional assessment in Alzheimer's disease

2010 ◽  
Vol 23 (2) ◽  
pp. 333-334
Author(s):  
V M Aziz ◽  
J. Yagoub ◽  
K. Saba ◽  
M. Asaad
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Assessment ◽  
Clinical Picture ◽  
Behavioral Changes ◽  
Cognitive Domains ◽  
Amnesic Syndrome ◽  
Insidious Onset ◽  
Progressive Cognitive Impairment

Alzheimer's disease (AD) manifests clinically with an insidious onset and slow but progressive cognitive impairment. The clinical picture of AD can be classified into cognitive and behavioral changes. The initial deficit usually manifests as an amnesic syndrome which may progress very gradually for several years before impairment in other cognitive domains, such as language, semantic memory and visuospatial function, becomes apparent (Hodges and Patterson, 1995).

Probable Alzheimer's Disease Patients Presenting as “Focal Temporal Lobe Dysfunction” Show a Slow Rate of Cognitive Decline

2011 ◽  
Vol 18 (1) ◽  
pp. 144-150 ◽  
Author(s):  
Camillo Marra ◽  
Giampiero Villa ◽  
Davide Quaranta ◽  
Alessandro Valenza ◽  
Maria Gabriella Vita ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Semantic Memory ◽  
Temporal Lobe ◽  
Memory Impairment ◽  
Anterograde Amnesia ◽  
Continuous Series ◽  
Cognitive Domains ◽  
Rate Of Progression

AbstractSeveral authors have recently shown that anterograde amnesia is often associated with semantic memory impairment in amnesic MCI patients. Similarly, after the MCI condition, some patients who convert to Alzheimer's disease (AD) show the classic onset (cAD) characterized by the impairment of memory and executive functions, whereas other AD patients show isolated defects of episodic and semantic memory without deficits in other cognitive domains. The latter have been considered an AD variant characterized by ‘focal Temporal Lobe Dysfunction’ (TLD). The aim of the present study was to assess the differences in disease progression between cAD and TLD. For this purpose a continuous series of newly diagnosed probable AD patients presenting as cAD (n = 30) and TLD (n = 25), matched for severity, and 65 healthy controls underwent a comprehensive neuropsychological evaluation at baseline; TLD and cAD were re-evaluated at a 24-month follow-up. At follow-up, TLD patients showed no significant worsening of cognitive functions, whereas cAD subjects displayed a significant worsening in all explored cognitive domains. In conclusion, our results confirm that probable AD presenting as TLD represents a specific onset of AD characterized by a slower rate of progression. (JINS, 2012, 18, 144–150)

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