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  1. Article ; Online: Introduction to the special issue on brain health.

    Gorelick, Philip B / Hainsworth, Atticus H / Wallin, Anders

    Cerebral circulation - cognition and behavior

    2024  Volume 6, Page(s) 100208

    Abstract: None. ...

    Abstract None.
    Language English
    Publishing date 2024-01-18
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-2450
    ISSN (online) 2666-2450
    DOI 10.1016/j.cccb.2024.100208
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  2. Article ; Online: What will it take to achieve brain health globally?

    Gorelick, Philip B / Hainsworth, Atticus H / Wallin, Anders

    Cerebral circulation - cognition and behavior

    2024  Volume 6, Page(s) 100209

    Abstract: Brain health initiatives and programs are gaining traction worldwide. Some are clinically based, others research based, and some are a combination of clinical and research action plans. Achievement of global brain health is a challenging endeavor with ... ...

    Abstract Brain health initiatives and programs are gaining traction worldwide. Some are clinically based, others research based, and some are a combination of clinical and research action plans. Achievement of global brain health is a challenging endeavor with prerequisites including but not limited to multidisciplinary and multisectoral approaches, strengthening of neurologic policies at local and regional levels, global advocacy, leadership and collaboration amongst stakeholders, development of technical and guidance documents, and strengthening and interpretation of the relevant evidence. Over 1 billion persons worldwide are impacted by neurologic disorders, and brain health initiatives are needed to curb the human suffering and cost of these disorders. We provide a brief review of select brain health initiatives and programs and offer possible steps to achieve brain health globally.
    Language English
    Publishing date 2024-01-28
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-2450
    ISSN (online) 2666-2450
    DOI 10.1016/j.cccb.2024.100209
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  3. Article ; Online: White matter lesions in cerebral small vessel disease: Underperfusion or leaky vessels?

    Hainsworth, Atticus H

    Neurology

    2019  Volume 92, Issue 15, Page(s) 687–688

    MeSH term(s) Blood-Brain Barrier ; Brain ; Cerebral Small Vessel Diseases ; Humans ; Vascular Diseases ; White Matter
    Language English
    Publishing date 2019-03-13
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000007258
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  4. Article ; Online: Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia.

    Hainsworth, Atticus H / Markus, Hugh S / Schneider, Julie A

    Hypertension (Dallas, Tex. : 1979)

    2023  Volume 81, Issue 1, Page(s) 75–86

    Abstract: Hypertension-associated cerebral small vessel disease is a common finding in older people. Strongly associated with age and hypertension, small vessel disease is found at autopsy in over 50% of people aged ≥65 years, with a spectrum of clinical ... ...

    Abstract Hypertension-associated cerebral small vessel disease is a common finding in older people. Strongly associated with age and hypertension, small vessel disease is found at autopsy in over 50% of people aged ≥65 years, with a spectrum of clinical manifestations. It is the main cause of lacunar stroke and a major source of vascular contributions to cognitive impairment and dementia. The brain areas affected are subcortical and periventricular white matter and deep gray nuclei. Neuropathological sequelae are diffuse white matter lesions (seen as white matter hyperintensities on T2-weighted magnetic resonance imaging), small ischemic foci (lacunes or microinfarcts), and less commonly, subcortical microhemorrhages. The most common form of cerebral small vessel disease is concentric, fibrotic thickening of small penetrating arteries (up to 300 microns outer diameter) termed arteriolosclerosis. Less common forms are small artery atheroma and lipohyalinosis (the lesions described by C. Miller Fisher adjacent to lacunes). Other microvascular lesions that are not reviewed here include cerebral amyloid angiopathy and venous collagenosis. Here, we review the epidemiology, neuropathology, clinical management, genetics, preclinical models, and pathogenesis of hypertensive small vessel disease. Knowledge gaps include initiating factors, molecular pathogenesis, relationships between arterial pathology and tissue damage, possible reversibility, pharmacological targets, and molecular biomarkers. Progress is anticipated from multicell transcriptomic and proteomic profiling, novel experimental models and further target-finding and interventional clinical studies.
    MeSH term(s) Humans ; Aged ; Proteomics ; Cerebral Small Vessel Diseases/complications ; Hypertension/epidemiology ; Hypertension/complications ; Dementia/etiology ; Dementia/complications ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/complications ; Magnetic Resonance Imaging ; Dementia, Vascular/epidemiology ; Dementia, Vascular/etiology
    Language English
    Publishing date 2023-11-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.123.19943
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  5. Article ; Online: An introduction to therapeutic approaches to vascular cognitive impairment.

    Hainsworth, Atticus H / Elahi, Fanny M / Corriveau, Roderick A

    Cerebral circulation - cognition and behavior

    2021  Volume 2, Page(s) 100033

    Abstract: Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the "second-most common dementia" after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular ... ...

    Abstract Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the "second-most common dementia" after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular disease. There are no validated pharmacological targets for prevention or treatment of VCI. This has inspired a multitude of potential treatment approaches, reflected by the articles in this Special Issue. These include
    Language English
    Publishing date 2021-12-09
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2666-2450
    ISSN (online) 2666-2450
    DOI 10.1016/j.cccb.2021.100033
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  6. Article ; Online: PDE5 inhibitor drugs for use in dementia.

    Hainsworth, Atticus H / Arancio, Ottavio / Elahi, Fanny M / Isaacs, Jeremy D / Cheng, Feixiong

    Alzheimer's & dementia (New York, N. Y.)

    2023  Volume 9, Issue 3, Page(s) e12412

    Abstract: Alzheimer's disease and related dementias (ADRD) remain a major health-care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase-5 (PDE5) is widely expressed in vascular myocytes, ... ...

    Abstract Alzheimer's disease and related dementias (ADRD) remain a major health-care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase-5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia. Potent, selective, Food and Drug Administration-approved PDE5 inhibitors are already in clinical use (sildenafil, vardenafil, tadalafil) as vasodilators in erectile dysfunction and pulmonary arterial hypertension. Animal data indicate cognitive benefits of PDE5 inhibitors. In humans, real-world patient data suggest that sildenafil and vardenafil are associated with reduced dementia risk. While a recent clinical trial of acute tadalafil on cerebral blood flow was neutral, there may be chronic actions of PDE5 inhibition on cerebrovascular or synaptic function. We provide a perspective on the potential utility of PDE5 inhibitors for ADRD. We conclude that further prospective clinical trials with PDE5 inhibitors are warranted. The choice of drug will depend on brain penetration, tolerability in older people, half-life, and off-target effects.
    Highlights: Potent phosphodiesterase-5 (PDE5) inhibitors are in clinical use as vasodilators.In animals PDE5 inhibitors enhance synaptic function and cognitive ability.In humans the PDE5 inhibitor sildenafil is associated with reduced risk of Alzheimer's disease.Licensed PDE5 inhibitors have potential for repurposing in dementia.Prospective clinical trials of PDE5 inhibitors are warranted.
    Language English
    Publishing date 2023-09-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2832891-7
    ISSN 2352-8737 ; 2352-8737
    ISSN (online) 2352-8737
    ISSN 2352-8737
    DOI 10.1002/trc2.12412
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  7. Article ; Online: An introduction to therapeutic approaches to vascular cognitive impairment

    Atticus H Hainsworth / Fanny M Elahi / Roderick A Corriveau

    Cerebral Circulation, Cognition and Behavior, Vol 2, Iss , Pp 100033- (2021)

    2021  

    Abstract: Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the “second-most common dementia” after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular ... ...

    Abstract Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the “second-most common dementia” after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular disease. There are no validated pharmacological targets for prevention or treatment of VCI. This has inspired a multitude of potential treatment approaches, reflected by the articles in this Special Issue. These include in vitro testing of the novel oral anticoagulant dabigatran for protection against β-amyloid neurotoxicity, and an overview of neuroinflammation in VCI and the role of circulating markers (PIGF, VEGF-D) identified by the MarkVCID study. There are reviews of potential therapeutics, including adrenomedullin and nootropic preparations (exemplified by cerebrolysin). The role of sleep is reviewed, with possible therapeutic targets (5HT2A receptors). There is a clinical study protocol (INVESTIGATE-SVD) and a feasibility analysis for a secondary prevention trial in small vessel disease. Clinical data include secondary analyses of blood pressure and cerebral blood flow from a longitudinal clinical trial (NILVAD), differences between methylphenidate and galantamine responders and non-responders (STREAM-VCI), appraisal of treatment approaches in India, and primary outcomes from a randomised trial of Argentine tango dancing to preserve cognition in African American women (ACT). Treating vascular disease has great potential to improve global cognitive health, with public health impacts alongside individual benefit. Vascular disease burden varies across populations, offering the possibility of proactively addressing health inequity in dementia using vascular interventions. The next 5–10 years will witness cost-effective lifestyle interventions, repurposed drugs and novel therapeutics.
    Keywords Vascular cognitive impairment ; VCID ; Vascular dementia ; Treatments ; Clinical trials ; Drugs ; Specialties of internal medicine ; RC581-951 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A dysfunctional blood-brain barrier and cerebral small vessel disease.

    Hainsworth, Atticus H / Fisher, Mark J

    Neurology

    2016  Volume 88, Issue 5, Page(s) 420–421

    MeSH term(s) Biological Transport ; Blood-Brain Barrier ; Brain ; Cerebral Small Vessel Diseases ; Humans
    Keywords covid19
    Language English
    Publishing date 2016-12-28
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000003561
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  9. Article ; Online: Association of White Matter Hyperintensities and Cardiovascular Disease: The Importance of Microcirculatory Disease.

    Moroni, Francesco / Ammirati, Enrico / Hainsworth, Atticus H / Camici, Paolo G

    Circulation. Cardiovascular imaging

    2020  Volume 13, Issue 8, Page(s) e010460

    Abstract: Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue ... ...

    Abstract Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.
    MeSH term(s) Animals ; Cerebral Small Vessel Diseases/diagnostic imaging ; Cerebral Small Vessel Diseases/epidemiology ; Cerebral Small Vessel Diseases/physiopathology ; Cerebrovascular Circulation ; Coronary Circulation ; Heart Diseases/diagnostic imaging ; Heart Diseases/epidemiology ; Heart Diseases/physiopathology ; Humans ; Leukoencephalopathies/diagnostic imaging ; Leukoencephalopathies/epidemiology ; Leukoencephalopathies/physiopathology ; Magnetic Resonance Imaging ; Microcirculation ; Prevalence ; Prognosis ; Risk Assessment ; Risk Factors ; White Matter/blood supply ; White Matter/diagnostic imaging
    Language English
    Publishing date 2020-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2435045-X
    ISSN 1942-0080 ; 1941-9651
    ISSN (online) 1942-0080
    ISSN 1941-9651
    DOI 10.1161/CIRCIMAGING.120.010460
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  10. Article ; Online: ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.

    Panahi, Mahmod / Hase, Yoshiki / Gallart-Palau, Xavier / Mitra, Sumonto / Watanabe, Atsushi / Low, Roger C / Yamamoto, Yumi / Sepulveda-Falla, Diego / Hainsworth, Atticus H / Ihara, Masafumi / Sze, Siu Kwan / Viitanen, Matti / Behbahani, Homira / Kalaria, Raj N

    Acta neuropathologica communications

    2023  Volume 11, Issue 1, Page(s) 76

    Abstract: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of ... ...

    Abstract Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear. Focusing on cerebral microvessels in the frontal and anterior temporal lobes and the basal ganglia, we used advanced proteomic and immunohistochemical methods to explore the extent of inflammatory and immune responses in CADASIL subjects compared to similar age normal and other disease controls. There was variable loss of VSMC in medial layers of arteries in white matter as well as the cortex, that could not be distinguished whether NOTCH3 mutations were in the epidermal growth factor (EGFr) domains 1-6 or EGFr7-34. Proteomics of isolated cerebral microvessels showed alterations in several proteins, many associated with endoplasmic reticulum (ER) stress including heat shock proteins. Cerebral vessels with sparsely populated VSMCs also attracted robust accrual of perivascular microglia/macrophages in order CD45
    MeSH term(s) Humans ; CADASIL/genetics ; Intercellular Adhesion Molecule-1 ; Proteomics ; Complement System Proteins ; Cerebral Infarction
    Chemical Substances Intercellular Adhesion Molecule-1 (126547-89-5) ; Complement System Proteins (9007-36-7)
    Language English
    Publishing date 2023-05-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-023-01558-1
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