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  1. Article ; Online: Common infections and increased risk of developing dementia: compelling evidence for intervention studies.

    Holmes, Clive

    The Lancet. Healthy longevity

    2021  Volume 2, Issue 7, Page(s) e391–e392

    MeSH term(s) Dementia/epidemiology ; Humans
    Language English
    Publishing date 2021-06-18
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2666-7568
    ISSN (online) 2666-7568
    DOI 10.1016/S2666-7568(21)00147-1
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  2. Book: Advances in old age psychiatry

    Holmes, Clive

    chromosomes to community care

    1997  

    Author's details ed. by Clive Holmes
    Keywords Mental Disorders / in old age ; Mental Disorders / therapy ; Geriatric Psychiatry / methods
    Language English
    Size IX, 284 S. : Ill.
    Publisher Wrightson
    Publishing place Petersfield u.a.
    Publishing country Great Britain
    Document type Book
    HBZ-ID HT007713216
    ISBN 1-871816-34-3 ; 978-1-871816-34-1
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    1997 A 6920 order for loan Magazin

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  3. Article ; Online: Author Response.

    Holmes, Clive

    Neurology

    2015  Volume 85, Issue 23, Page(s) 2084

    MeSH term(s) Alzheimer Disease/drug therapy ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Female ; Humans ; Immunoglobulin G/pharmacology ; Male ; Tumor Necrosis Factor-alpha/antagonists & inhibitors
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Immunoglobulin G ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2015-12-08
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
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  4. Article ; Online: Changes in the locus coeruleus during the course of Alzheimer's disease and their relationship to cortical pathology.

    Beardmore, Rebecca / Durkin, Matthew / Zayee-Mellick, Faizan / Lau, Laurie C / Nicoll, James A R / Holmes, Clive / Boche, Delphine

    Neuropathology and applied neurobiology

    2024  Volume 50, Issue 1, Page(s) e12965

    Abstract: Aims: In Alzheimer's disease (AD), the locus coeruleus (LC) undergoes early and extensive neuronal loss, preceded by abnormal intracellular tau aggregation, decades before the onset of clinical disease. Neuromelanin-sensitive MRI has been proposed as a ... ...

    Abstract Aims: In Alzheimer's disease (AD), the locus coeruleus (LC) undergoes early and extensive neuronal loss, preceded by abnormal intracellular tau aggregation, decades before the onset of clinical disease. Neuromelanin-sensitive MRI has been proposed as a method to image these changes during life. Surprisingly, human post-mortem studies have not examined how changes in LC during the course of the disease relate to cerebral pathology following the loss of the LC projection to the cortex.
    Methods: Immunohistochemistry was used to examine markers for 4G8 (pan-Aβ) and AT8 (ptau), LC integrity (neuromelanin, dopamine β-hydroxylase [DβH], tyrosine hydroxylase [TH]) and microglia (Iba1, CD68, HLA-DR) in the LC and related temporal lobe pathology of 59 post-mortem brains grouped by disease severity determined by Braak stage (0-II, III-IV and V-VI). The inflammatory environment was assessed using multiplex assays.
    Results: Changes in the LC with increasing Braak stage included increased neuronal loss (p < 0.001) and microglial Iba1 (p = 0.005) together with a reduction in neuromelanin (p < 0.001), DβH (p = 0.002) and TH (p = 0.041). Interestingly in LC, increased ptau and loss of neuromelanin were detected from Braak stage III-IV (p = 0.001). At Braak stage V/VI, the inflammatory environment was different in the LC vs TL, highlighting the anatomical heterogeneity of the inflammatory response.
    Conclusions: Here, we report the first quantification of neuromelanin during the course of AD and its relationship to AD pathology and neuroinflammation in the TL. Our findings of neuromelanin loss early in AD and before the neuroinflammatory reaction support the use of neuromelanin-MRI as a sensitive technique to identify early changes in AD.
    MeSH term(s) Humans ; Alzheimer Disease/pathology ; Locus Coeruleus/metabolism ; tau Proteins/metabolism ; Brain/pathology ; Autopsy
    Chemical Substances tau Proteins
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 80371-6
    ISSN 1365-2990 ; 0305-1846
    ISSN (online) 1365-2990
    ISSN 0305-1846
    DOI 10.1111/nan.12965
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  5. Article ; Online: Intravenous immunoglobulin for Alzheimer's disease.

    Holmes, Clive

    The Lancet. Neurology

    2013  Volume 12, Issue 3, Page(s) 218–219

    MeSH term(s) Alzheimer Disease/drug therapy ; Alzheimer Disease/immunology ; Female ; Humans ; Immunoglobulins, Intravenous/administration & dosage ; Male
    Chemical Substances Immunoglobulins, Intravenous
    Language English
    Publishing date 2013-03
    Publishing country England
    Document type Comment ; Journal Article
    ZDB-ID 2079704-7
    ISSN 1474-4465 ; 1474-4422
    ISSN (online) 1474-4465
    ISSN 1474-4422
    DOI 10.1016/S1474-4422(13)70015-2
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  6. Article ; Online: The Locus Coeruleus in Aging and Alzheimer's Disease: A Postmortem and Brain Imaging Review.

    Beardmore, Rebecca / Hou, Ruihua / Darekar, Angela / Holmes, Clive / Boche, Delphine

    Journal of Alzheimer's disease : JAD

    2021  Volume 83, Issue 1, Page(s) 5–22

    Abstract: The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of ... ...

    Abstract The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer's disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.
    MeSH term(s) Aging/pathology ; Alzheimer Disease/pathology ; Animals ; Autopsy ; Brain Stem ; Humans ; Locus Coeruleus/diagnostic imaging ; Locus Coeruleus/pathology ; Magnetic Resonance Imaging ; Melanins/pharmacology ; Mice ; Norepinephrine/metabolism ; Rats ; tau Proteins/metabolism
    Chemical Substances Melanins ; neuromelanin ; tau Proteins ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2021-07-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-210191
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  7. Article ; Online: A case-control study of the locus coeruleus degeneration in Alzheimer's disease.

    Hou, Ruihua / Beardmore, Rebecca / Holmes, Clive / Osmond, Clive / Darekar, Angela

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

    2021  Volume 43, Page(s) 153–159

    Abstract: The locus coeruleus (LC) is the major source of noradrenaline, which plays a key role in cognition. We aimed to detect the extent of the LC signal attenuation in Alzheimer's disease (AD) patients using a neuromelanin (NM)-sensitive MRI and how it may ... ...

    Abstract The locus coeruleus (LC) is the major source of noradrenaline, which plays a key role in cognition. We aimed to detect the extent of the LC signal attenuation in Alzheimer's disease (AD) patients using a neuromelanin (NM)-sensitive MRI and how it may correlate with inflammatory and autonomic measures. An individually matched case-control study design was employed. 24 patients with AD and 24 age and gender matched controls with no cognitive impairment were recruited. The primary outcome measure was the LC signal intensity indicated by the LC contrast ratio (CR) and measured by the NM-sensitive MRI. Secondary outcome measures included neuropsychometric tests of cognitive state, peripheral inflammatory and autonomic measures. Conditional logistic regression analysis revealed a significant 22% LC-CR reduction in the AD group compared with the control group. However, there was no statistical significance from inflammatory or autonomic measures. This is the largest individually-matched case-control study to visualise the LC degeneration in AD patients. The study revealed significant LC degeneration which holds promise to stratify patients who may benefit from treatment targeting noradrenergic dysfunction.
    MeSH term(s) Alzheimer Disease/diagnostic imaging ; Case-Control Studies ; Cognitive Dysfunction ; Humans ; Locus Coeruleus ; Magnetic Resonance Imaging
    Language English
    Publishing date 2021-01-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1082947-7
    ISSN 1873-7862 ; 0924-977X
    ISSN (online) 1873-7862
    ISSN 0924-977X
    DOI 10.1016/j.euroneuro.2020.12.013
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  8. Article: Associated mortality risk of atypical antipsychotic medication in individuals with dementia.

    Phiri, Peter / Engelthaler, Tomas / Carr, Hannah / Delanerolle, Gayathri / Holmes, Clive / Rathod, Shanaya

    World journal of psychiatry

    2022  Volume 12, Issue 2, Page(s) 298–307

    Abstract: Background: Antipsychotic medications such as risperidone, olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients. Current evidence indicate prescription rates for antipsychotics vary and wider ... ...

    Abstract Background: Antipsychotic medications such as risperidone, olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients. Current evidence indicate prescription rates for antipsychotics vary and wider consensus to evaluate clinical epidemiological outcomes is limited.
    Aim: To investigate the potential impact of atypical antipsychotics on the mortality of patients with dementia.
    Methods: A retrospective clinical cohort study was developed to review United Kingdom Clinical Record Interactive Search system based data between January 1, 2013 to December 31, 2017. A descriptive statistical method was used to analyse the data. Mini Mental State Examination (MMSE) scores were used to assess the severity and stage of disease progression. A cox proportional hazards model was developed to evaluate the relationship between survival following diagnosis and other variables.
    Results: A total of 1692 patients were identified using natural language processing of which, 587 were prescribed olanzapine, quetiapine or risperidone (common group) whilst 893 (control group) were not prescribed any antipsychotics. Patients prescribed olanzapine showed an increased risk of death [hazard ratio (HR) = 1.32; 95% confidence interval (CI): 1.08-1.60;
    Conclusion: A significant mortality risk was identified among those prescribed olanzapine and risperidone which contradicts previous findings although the study designs used were different. Comprehensive research should be conducted to better assess clinical epidemiological outcomes associated with diagnosis and therapies to improve clinical management of these patients.
    Language English
    Publishing date 2022-02-19
    Publishing country United States
    Document type Journal Article
    ISSN 2220-3206
    ISSN 2220-3206
    DOI 10.5498/wjp.v12.i2.298
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  9. Article: Vagus Nerve Stimulation as a Potential Therapy in Early Alzheimer's Disease: A Review.

    Vargas-Caballero, Mariana / Warming, Hannah / Walker, Robert / Holmes, Clive / Cruickshank, Garth / Patel, Bipin

    Frontiers in human neuroscience

    2022  Volume 16, Page(s) 866434

    Abstract: Cognitive dysfunction in Alzheimer's disease (AD) is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance ... ...

    Abstract Cognitive dysfunction in Alzheimer's disease (AD) is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulation (VNS),
    Language English
    Publishing date 2022-04-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2425477-0
    ISSN 1662-5161
    ISSN 1662-5161
    DOI 10.3389/fnhum.2022.866434
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  10. Article ; Online: The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug.

    Marr, Calum / McDowell, Bethany / Holmes, Clive / Edwards, Christopher J / Cardwell, Christopher / McHenry, Michelle / Meenagh, Gary / Teeling, Jessica L / McGuinness, Bernadette

    Journal of Alzheimer's disease : JAD

    2024  Volume 99, Issue 1, Page(s) 161–175

    Abstract: Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer's disease progression by reducing inflammation.: Objective: To investigate whether RA patients with mild cognitive ... ...

    Abstract Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer's disease progression by reducing inflammation.
    Objective: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD).
    Methods: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA).
    Results: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = -1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = -0.4, 1.3).
    Conclusions: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.
    Language English
    Publishing date 2024-04-26
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-231329
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