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  1. Article ; Online: Lung function and risk of incident dementia: A prospective cohort study of 431,834 individuals.

    Ma, Ya-Hui / Shen, Ling-Xiao / Li, Yu-Zhu / Leng, Yue / Yang, Liu / Chen, Shi-Dong / He, Xiao-Yu / Zhang, Ya-Ru / Chen, Ren-Jie / Feng, Jian-Feng / Tan, Lan / Dong, Qiang / Suckling, John / David Smith, A / Cheng, Wei / Yu, Jin-Tai

    Brain, behavior, and immunity

    2023  Volume 109, Page(s) 321–330

    Abstract: Background: Whether lung function prospectively affects cognitive brain health independent of their overlapping factors remains largely unknown. This study aimed to investigate the longitudinal association between decreased lung function and cognitive ... ...

    Abstract Background: Whether lung function prospectively affects cognitive brain health independent of their overlapping factors remains largely unknown. This study aimed to investigate the longitudinal association between decreased lung function and cognitive brain health and to explore underlying biological and brain structural mechanisms.
    Methods: This population-based cohort included 43,1834 non-demented participants with spirometry from the UK Biobank. Cox proportional hazard models were fitted to estimate the risk of incident dementia for individuals with low lung function. Mediation models were regressed to explore the underlying mechanisms driven by inflammatory markers, oxygen-carrying indices, metabolites, and brain structures.
    Findings: During a follow-up of 3,736,181 person-years (mean follow-up 8.65 years), 5,622 participants (1.30 %) developed all-cause dementia, which consisted of 2,511 Alzheimer's dementia (AD) and 1,308 Vascular Dementia (VD) cases. Per unit decrease in lung function measure was each associated with increased risk for all-cause dementia (forced expiratory volume in 1 s [liter]: hazard ratio [HR, 95 %CI], 1.24 [1.14-1.34], P = 1.10 × 10
    Interpretation: Life-course risk for incident dementia was modulated by individual lung function. Maintaining optimal lung function is useful for healthy aging and dementia prevention.
    MeSH term(s) Humans ; Prospective Studies ; Alzheimer Disease ; Brain ; Lung ; Oxygen ; Risk Factors
    Chemical Substances Oxygen (S88TT14065)
    Language English
    Publishing date 2023-02-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2023.02.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Identifying modifiable factors and their joint effect on dementia risk in the UK Biobank.

    Zhang, Yi / Chen, Shi-Dong / Deng, Yue-Ting / You, Jia / He, Xiao-Yu / Wu, Xin-Rui / Wu, Bang-Sheng / Yang, Liu / Zhang, Ya-Ru / Kuo, Kevin / Feng, Jian-Feng / Cheng, Wei / Suckling, John / David Smith, A / Yu, Jin-Tai

    Nature human behaviour

    2023  Volume 7, Issue 7, Page(s) 1185–1195

    Abstract: Previous hypothesis-driven research has identified many risk factors linked to dementia. However, the multiplicity and co-occurrence of risk factors have been underestimated. Here we analysed data of 344,324 participants from the UK Biobank with 15 yr of ...

    Abstract Previous hypothesis-driven research has identified many risk factors linked to dementia. However, the multiplicity and co-occurrence of risk factors have been underestimated. Here we analysed data of 344,324 participants from the UK Biobank with 15 yr of follow-up data for 210 modifiable risk factors. We first conducted an exposure-wide association study and then combined factors associated with dementia to generate composite scores for different domains. We then evaluated their joint associations with dementia in a multivariate Cox model. We estimated the potential impact of eliminating the unfavourable profiles of risk domains on dementia using population attributable fraction. The associations varied by domain, with lifestyle (16.6%), medical history (14.0%) and socioeconomic status (13.5%) contributing to the majority of dementia cases. Overall, we estimated that up to 47.0%-72.6% of dementia cases could be prevented.
    MeSH term(s) Humans ; Dementia/epidemiology ; Dementia/etiology ; Dementia/prevention & control ; Biological Specimen Banks ; Risk Factors ; Life Style ; United Kingdom/epidemiology
    Language English
    Publishing date 2023-04-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2397-3374
    ISSN (online) 2397-3374
    DOI 10.1038/s41562-023-01585-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A Machine Learning Approach to Identify a Circulating MicroRNA Signature for Alzheimer Disease.

    Zhao, Xuemei / Kang, John / Svetnik, Vladimir / Warden, Donald / Wilcock, Gordon / David Smith, A / Savage, Mary J / Laterza, Omar F

    The journal of applied laboratory medicine

    2019  Volume 5, Issue 1, Page(s) 15–28

    Abstract: Background: Accurate diagnosis of Alzheimer disease (AD) involving less invasive molecular procedures and at reasonable cost is an unmet medical need. We identified a serum miRNA signature for AD that is less invasive than a measure in cerebrospinal ... ...

    Abstract Background: Accurate diagnosis of Alzheimer disease (AD) involving less invasive molecular procedures and at reasonable cost is an unmet medical need. We identified a serum miRNA signature for AD that is less invasive than a measure in cerebrospinal fluid.
    Methods: From the Oxford Project to Investigate Memory and Aging (OPTIMA) study, 96 serum samples were profiled by a multiplex (>500 analytes) microRNA (miRNA) reverse transcription quantitative PCR analysis, including 51 controls, 32 samples from patients with AD, and 13 samples from patients with mild cognitive impairment (MCI). Clinical diagnosis of a subset of AD and the controls was confirmed by postmortem (PM) histologic examination of brain tissue. In a machine learning approach, the AD and control samples were split 70:30 as the training and test cohorts. A multivariate random forest statistical analysis was applied to construct and test a miRNA signature for AD identification. In addition, the MCI participants were included in the test cohort to assess whether the signature can identify early AD patients.
    Results: A 12-miRNA signature for AD identification was constructed in the training cohort, demonstrating 76.0% accuracy in the independent test cohort with 90.0% sensitivity and 66.7% specificity. The signature, however, was not able to identify MCI participants. With a subset of AD and control participants with PM-confirmed diagnosis status, a separate 12-miRNA signature was constructed. Although sample size was limited, the PM-confirmed signature demonstrated improved accuracy of 85.7%, largely owing to improved specificity of 80.0% with comparable sensitivity of 88.9%.
    Conclusion: Although additional and more diverse cohorts are needed for further clinical validation of the robustness, the miRNA signature appears to be a promising blood test to diagnose AD.
    MeSH term(s) Aged ; Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/mortality ; Autopsy/methods ; Brain/metabolism ; Brain/pathology ; Circulating MicroRNA/blood ; Cognitive Dysfunction/cerebrospinal fluid ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/genetics ; Early Diagnosis ; Female ; Gene Expression Profiling/methods ; Humans ; Machine Learning ; Male ; Reproducibility of Results ; Sensitivity and Specificity ; Transcriptome
    Chemical Substances Circulating MicroRNA
    Language English
    Publishing date 2019-11-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2576-9456
    ISSN 2576-9456
    DOI 10.1373/jalm.2019.029595
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  4. Article: Specific antibodies to bovine choline acetyltransferase raised in mice immunised with small amounts of partially purified enzyme.

    Eder-Colli, L / Powell, J F / Claudio Cuello, A / David Smith, A

    Neurochemistry international

    2009  Volume 4, Issue 5, Page(s) 383–388

    Abstract: Choline acetyltransferase was purified approximately 18,000-fold from 300 g of bovine caudate nuclei to a specific activity of 21 ?mol min mg protein. The overall procedure used was: extraction of the enzyme by high salt concentration, chromatography on ... ...

    Abstract Choline acetyltransferase was purified approximately 18,000-fold from 300 g of bovine caudate nuclei to a specific activity of 21 ?mol min mg protein. The overall procedure used was: extraction of the enzyme by high salt concentration, chromatography on carboxy-methyl-Sephadex, precipitation by ammonium sulphate, affinity chromatography on Blue-Sepharose and, finally absorption on hydroxylapatite. When the enzyme absorbed on hydroxylapatite was injected into mice, it provoked reproducibly a transient production of 'inhibitory' antibodies, followed by higher antibody titres mainly of 'non-inhibitory' type. These responses were elicited by injecting less than a total of 20 ?g of immunogen. The highest antibody titre was obtained less than 2 months following the initial immunisation. Species cross reactivity was investigated. This procedure should prove to be of value in the production of monoclonal antibodies to choline acetyltransferase.
    Language English
    Publishing date 2009-11-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 283190-9
    ISSN 1872-9754 ; 0197-0186
    ISSN (online) 1872-9754
    ISSN 0197-0186
    DOI 10.1016/0197-0186(82)90080-8
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  5. Article: Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method.

    Hogervorst, Eef / Williams, Jonathan / Combrinck, Marc / David Smith, A

    European journal of endocrinology

    2003  Volume 148, Issue 1, Page(s) 67–72

    Abstract: Objective: Oestrogens could be protective against the development of Alzheimer's disease (AD) but reports on oestrogen levels in AD have been conflicting.: Design and methods: A meta-analysis using robust regression was carried out to assess whether ... ...

    Abstract Objective: Oestrogens could be protective against the development of Alzheimer's disease (AD) but reports on oestrogen levels in AD have been conflicting.
    Design and methods: A meta-analysis using robust regression was carried out to assess whether the sensitivity of the assays of past studies had affected the reported level of total oestradiol. We had also measured total oestradiol in women with AD (n=66) and controls (n=62) not using hormone replacement therapy. We used two assays for total oestradiol to assess the difference between sensitive (radioimmunoassay with a specific rabbit antibody: 3 pmol/l) and relatively insensitive (immunoassay: 37 pmol/l) assays.
    Results: Meta-analysis using robust regression indicated that insensitive assays gave higher levels of total oestradiol when many samples fall below the level of sensitivity of the method. Earlier reports of low levels of total oestradiol in AD might be explained by this phenomenon, since total oestradiol levels (using the sensitive assay) in our controls were one third of those reported in the earlier studies. Using the sensitive assay we found that women with AD had significantly (P<0.01) higher levels (26+/-13 pmol/l) of total oestradiol than controls (21+/-13 pmol/l). Using the insensitive assay, there was no significant difference in the levels of total oestradiol.
    Conclusions: The sensitivity of the assay determines the reported value of the oestradiol levels. Studies using a sensitive assay do not report significantly lower levels of total oestradiol in women with AD. This weighs against the hypothesis that low levels of total oestradiol are a risk factor for AD.
    MeSH term(s) Aged ; Aged, 80 and over ; Alzheimer Disease/blood ; Estradiol/blood ; Female ; Humans ; Immunoassay ; Radioimmunoassay ; Regression Analysis ; Sensitivity and Specificity
    Chemical Substances Estradiol (4TI98Z838E)
    Language English
    Publishing date 2003-01
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
    ZDB-ID 1183856-5
    ISSN 1479-683X ; 0804-4643
    ISSN (online) 1479-683X
    ISSN 0804-4643
    DOI 10.1530/eje.0.1480067
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  6. Article: Rate of progression of cognitive decline in Alzheimer's disease: effect of butyrylcholinesterase K gene variation.

    Holmes, C / Ballard, C / Lehmann, D / David Smith, A / Beaumont, H / Day, I N / Nadeem Khan, M / Lovestone, S / McCulley, M / Morris, C M / Munoz, D G / O'Brien, K / Russ, C / Del Ser, T / Warden, D

    Journal of neurology, neurosurgery, and psychiatry

    2005  Volume 76, Issue 5, Page(s) 640–643

    Abstract: Objective: To determine whether individuals with Alzheimer's disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase.: Method: The ... ...

    Abstract Objective: To determine whether individuals with Alzheimer's disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase.
    Method: The cognitive status of 339 community based subjects with AD was assessed with the Mini Mental State Examination at baseline and yearly over a three year follow up period. The rates of cognitive decline of subjects with and without the K variant allele were compared.
    Result: Presence of the K allele was associated with a slower average rate of cognitive decline in subjects with severe AD.
    Conclusions: This finding is consistent with the suggestion that the K variant of butyrylcholinesterase has an important role in disease progression in AD, and this may have implications for treatment.
    MeSH term(s) Aged ; Aged, 80 and over ; Alleles ; Alzheimer Disease/complications ; Alzheimer Disease/enzymology ; Alzheimer Disease/genetics ; Butyrylcholinesterase/genetics ; Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Cohort Studies ; Demography ; Female ; Genetic Variation ; Genotype ; Humans ; Male ; Neuropsychological Tests
    Chemical Substances Butyrylcholinesterase (EC 3.1.1.8)
    Language English
    Publishing date 2005-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3087-9
    ISSN 1468-330X ; 0022-3050
    ISSN (online) 1468-330X
    ISSN 0022-3050
    DOI 10.1136/jnnp.2004.039321
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  7. Article: Utility of the Malayalam translation of the 7- minute screen for Alzheimer's disease risk in an Indian community.

    de Jager, Celeste A / Thambisetty, Madhav / Praveen, K V / Sheeba, P D / Ajini, K N / Sajeev, A / Smitha, K K / Rahmathulla, L P / Ramakrishna, T / David, Smith A

    Neurology India

    2008  Volume 56, Issue 2, Page(s) 161–166

    Abstract: Background: Alzheimer's disease (AD) is suspected to be currently under-diagnosed in India, thus the need for a brief, effective screening test for the condition.: Aims: We aimed to test the Malayalam translation of the 7-Minute Screen (7MS) for ... ...

    Abstract Background: Alzheimer's disease (AD) is suspected to be currently under-diagnosed in India, thus the need for a brief, effective screening test for the condition.
    Aims: We aimed to test the Malayalam translation of the 7-Minute Screen (7MS) for detecting those at high risk for AD and to report on the subscores used to derive the Alzheimer's risk score.
    Setting and design: This study was performed in Kerala State amongst young university students and elders in residential care homes.
    Materials and methods: Two hundred and eighty-two volunteers were tested, 178 young controls (aged 20-29) and 104 literate elders, (55-92 years). None were clinically diagnosed with AD.
    Statistical analyses: Elders and controls were assessed as High or Low AD Risk with the published 7MS algorithm. Performance was compared between groups with ANOVA.
    Results: The algorithm estimated high (n=61/104) or low (n=40/104) AD risk in the elderly. Significant differences were found between controls, low- and high-risk groups on all four components of the screen (Orientation: F=131.1, Enhanced Cued Recall: F=23.4, Clock Drawing: F=65.1, Verbal Fluency: F=15.7, P<0.0001 for all) and in the risk scores (F=144.7, P<0.0001). Age and gender affected verbal fluency, orientation and clock drawing performance. The high-risk group had worse scores for orientation and better scores for memory than previously reported for AD cases in other populations.
    Conclusions: The 7MS may be a useful screening test for cognitive impairment in India. Suggestions are given for revising the 'risk algorithm' for more appropriate AD risk assessment in this population.
    MeSH term(s) Adult ; Age Factors ; Aged ; Aged, 80 and over ; Algorithms ; Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Alzheimer Disease/epidemiology ; Analysis of Variance ; Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Female ; Humans ; India/epidemiology ; Male ; Mass Screening/methods ; Middle Aged ; Neuropsychological Tests ; Residence Characteristics ; Risk Factors ; Surveys and Questionnaires ; Translating ; Young Adult
    Language English
    Publishing date 2008-08-01
    Publishing country India
    Document type Journal Article
    ZDB-ID 415522-1
    ISSN 1998-4022 ; 0028-3886
    ISSN (online) 1998-4022
    ISSN 0028-3886
    DOI 10.4103/0028-3886.41994
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