A solid body of evidence has accumulated over the past 20 years confirming the critical role of cerebrovascular disease in Alzheimer disease (AD) and other dementias of the aged.1–6 Most recently, data from the National Alzheimer's Coordinating Center7 demonstrated the presence of vascular pathology in 79.9% of 4,629 brains from patients with neuropathologically confirmed AD. Lesions included atherosclerosis in the circle of Willis, arteriosclerotic leukoencephalopathy, arteriolosclerosis, large infarcts, lacunes, multiple microinfarcts, and hemorrhages. Notably, cerebral amyloid angiopathy was present in less than half of the brains (40.8%). Given the absence of an effective treatment to halt the progression of AD, the current emphasis is on dementia prevention by appropriate treatment of vascular risk factors for stroke.8,9 Once stroke occurs, optimal treatment of the acute ictus with prompt restoration of flow in the occluded vessels improves the cognitive outcome. In contrast, stroke complications such as aspiration pneumonia, hypoxemia, seizures, hypotension, or cardiac arrhythmias increase the risk of poststroke cognitive impairment 4-fold.10
Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer’s disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.
Accessible online at: www.karger.com/journals/ned With the first issue of Neuroepidemiology in 2001, the journal begins its 20th year of continuous publication, advancing with confidence into the 21st century and the new millennium. Neuroepidemiology was founded in 1982 by Bruce S. Schoenberg – then Head, Section on Epidemiology, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Md., USA – with the purpose of providing an international forum for this ‘relatively new specialty... with a commitment to excellence and a dedication to clinically relevant topics’ [1]. During its first year, and despite its youth, the high scientific standard set by Dr. Schoenberg and the international editorial board for the new publication was recognized with an Award of Merit from the Society for Technical Communication. This standard of excellence has been maintained by the successive editors, F. Clifford Rose (1984–1988), Milton Alter (1989–1996) and, most recently (1997–2000), by my predecessor, Philip B. Gorelick, under whose direction the journal achieved a high impact index among both epidemiology and public health publications and neuroscience journals. It is, therefore, with some trepidation that I have accepted the appointment as Editorin-Chief, to take the helm of the journal to continue along the bearings set by my illustrious predecessors. From its beginnings, the quality of Neuroepidemiology has depended on its Deputy Editors, Editorial Board members and reviewers. For this reason, I am grateful to W.A. Rocca (Mayo Clinic, Rochester, Minn., USA) and W.T. Longstreth, Jr. (University of Washington, Seattle, Wash., USA), who have agreed to serve as Deputy Editors. Also, on behalf of the journal and its readership, I wish to thank the members of the Editorial Board that have completed their tour of service and to welcome the new members. One of the little-known roles of the Editorial Board members is to identify and encourage authors in their region – South America, Asia, India, the Middle East, Europe – to submit good-quality works to Neuroepidemiology; hopefully, this process will continue under the new group. Finally, I must recognize our publisher, S. Karger AG, Basel, and in particular Dr. Thomas Karger, for his long-standing commitment to the journal and for his personal interest in the continued success of Neuroepidemiology. For the new century, Neuroepidemiology has changed to a larger format, and the journal sports a new cover conserving the traditional colors and the image of the globe to convey the importance of international collaboration. The new logo combines the neuron and the Gaussian bell, easily identifiable emblems of our trade, the Table of
A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.
The few years elapsed since the publication of this chapter in the Second Edition of Dementia (2000) have seen the completion of a number of promising treatment trials in patients with vascular dementia (VaD). Moreover, successful enrolment for these studies demonstrated that by using strict criteria it is feasible to diagnose and identify patients with clinically unmixed VaD, and that the subjects recruited for these trials disclose clinical features and progression patterns that are clearly different from those observed in patient populations selected for clinical trials of Alzheimer disease (AD).
To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke.
Methods:
SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0–14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile.
Results:
Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85–0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75–2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001).
Conclusions:
In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.
AbstractCerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demostrated improvement in cognition, behavior and activites of daily living.Keywords: CEREBROVASCULAR DISEASEDEMENTIAELDERLYVASCULAR DEMENTIACHOLINESTERASE INHIBITORS
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