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• Your Company
  • Your Company’s Product(s)
• Cyberonics (2)
  • Alzheimer’s disease
  • VNS Therapy & Alzheimer's disease (1)
  • Cholinergic Neurotransmitter System
  • Neurostimulation
  • Neuromodulation
• [Boston Scientific Corporation, Inc. or Boston Scientific or BSCI] & Alzheimer’s disease
  • Cyberonics
  • Neurostimulation
  • Neuromodulation
• [St. Jude Medical or St. Jude] & Alzheimer’s disease
  • Cyberonics
  • Neurostimulation
  • Neuromodulation
• Alzheimer’s Disease or AD
  • Dementia (3)
  • Aphasia
  • Neuritic Plaque (2)
  • [Vagus or Vagal] Nerve Stimulation
  • VNS Tharapy
  • tacrine hydrochloride/ Cognex
  • donepezil/ Aricept
  • rivastigmine/ Exelon
  • Cholinergic Neurotransmitter System (1)
  • Neurostimulation
  • Neuromodulation

(A small sampling of results from a December 18, 2006 to January 12, 2007 MIB Abstract Alert search)

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Cyberonics' 10-K Report Audit Includes 'Going Concern' Qualification

Cyberonics Sends Letter to Stockholders

Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study.

The persistence of memory.

Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain.

Cyberonics' 10-K Report Audit Includes 'Going Concern' Qualification

PR Newswire. New York: Jan 12, 2007. pg. n/a

HOUSTON, Jan. 12 /PRNewswire-FirstCall/ -- Cyberonics, Inc. (Nasdaq: CYBX)("Company") noted today that its financial statements for the fiscal yearended April 28, 2006, included in the Company's Annual Report on Form 10-K("Form 10-K") filed on January 5, 2007, contain a going concern modificationto the audit opinion from its independent accounting firm, KPMG LLP. Aspreviously disclosed and discussed in Note 3 to the consolidated financialstatements in the Form 10-K, the going concern modification is based on theCompany's recurring losses from operations, a notice of alleged accelerationof its $125 million senior subordinated convertible notes, and a potentialdefault of its $40 million line of credit based on the alleged acceleration.

This announcement is being made in compliance with Nasdaq Marketplace Rule 4350(b)(1)(B), which requires separate disclosure of receipt of an audit opinion that contains a going concern qualification.

Proquest Identifier: 1193398501
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FDA Panel to Review Studies of Cyberonics Device

Wall Street Journal. (Eastern edition). New York, N.Y.: Dec 28, 2006. pg. D.4

A Food and Drug Administration advisory panel on neurological devices will review post-approval studies for a depression-treatment device made by Cyberonics Inc., but isn't likely to make moves that could affect the regulatory status for that device, an FDA spokeswoman said.

The panel of outside experts won't vote on anything regarding Cyberonics following the Jan. 26 meeting, which is intended to follow up on the status of studies that were required when the FDA approved the Cyberonics device for depression treatment last year, agency spokeswoman Karen Riley said. The meeting "will basically just be a discussion," she said.

In a statement, Cyberonics said that it would brief the FDA panel on the company's progress on the two studies the agency required and that both studies are enrolling patients. "These reports are part of the FDA's commitment to monitor the progress of post-market studies required as a condition of approval," the company said.

The company has had trouble winning reimbursement coverage for the pacemaker-like device, which the FDA approved in 2005 for the treatment of severe depression via stimulation of a nerve in the neck. If the FDA panel of outside experts makes comments or recommendations that could lead to new restrictions on the device, "it doesn't make the case for reimbursement any easier," said Stephen G. Brozak, an analyst with WBB Securities LLC.

The same FDA panel didn't unanimously recommend approval for the device in 2004, Mr. Brozak said, and the agency's approval process has generated some controversy. The Senate Finance Committee probed the matter and concluded this year that the FDA's approval process for the device raised some questions.

According to Ms. Riley, the panelists are "basically just going to listen," suggesting the meeting won't lead to major changes for Cyberonics. The event "would not be anything of major consequence," she said.

The FDA doesn't yet know what data will be presented, as such details are typically announced a day or so before the meeting. The agency typically publishes the name of involved companies at that point, too. In fact, the Federal Register posting Tuesday showing the involvement of Cyberonics and other companies represents the first time the agency has made such information available so far in advance, Ms. Riley said.

The move is part of an effort to increase transparency, she said. The panel also will review studies for a device made by Confluent Surgical, which was purchased by Tyco International Ltd. this year, and will discuss and make recommendations regarding an application for a depression-treatment system made by Neuronetics Inc.

The Cyberonics device is approved for the treatment of epilepsy. The FDA's approval for depression treatment required two follow-up, or post-market, studies regarding device performance. It is typical in such instances to hold later panel meetings to discuss the progress of those studies, Ms. Riley said.

Proquest Identifier: 1186462591
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Cyberonics Sends Letter to Stockholders

PR Newswire. New York: Jan 10, 2007. pg. n/a

Cyberonics is actively working with psychiatrists, patients, patient advocacy organizations, employers and payers to provide broad-based coverage policies. Our goal has been -- and continues to be -- to obtain broad-based national and regional coverage policy for Vagus Nerve Stimulation Therapy (VNS Therapy) in TRD more quickly than we did for refractory epilepsy. We are encouraged by the fact that a number of major regional payers are moving toward favorable coverage for VNS Therapy in TRD and are optimistic that the overwhelming public support for coverage from Centers for Medicare & Medicaid Services (CMS) will result in a favorable coverage policy.

We have also taken steps to renew and enhance our leadership team and build a stronger organization for the future. In November of 2006, Cyberonics announced that its Board had appointed [Reese S. Terry, Jr.] as Interim Chief Executive Officer. Mr. Terry is a co-founder of Cyberonics, a former member of the Company's management team, and was largely responsible for the development and application of Cyberonics' VNS Therapy. He has an unwavering commitment to Cyberonics and to our collective mission to improve the lives of people touched by epilepsy, depression and other chronic disorders that may prove treatable with our patented therapy.

These Definitive Additional Materials contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. These statements can be identified by the use of forward-looking terminology, including "may," "believe," "will," "expect," "anticipate," "estimate," "plan," "intend," and "forecast," or other similar words. Statements contained in these Definitive Additional Materials are based upon information presently available to the Company and assumptions that the Company believes to be reasonable. The Company is not assuming any duty to update this information should those facts change or should we no longer believe the assumptions to be reasonable. Investors are cautioned that all such statements involve risks and uncertainties, including without limitation, statements regarding financial performance, including improving sales in our epilepsy indication and improving international sales, product repositioning, development of favorable reimbursement coverage by CMS and other payers for VNS Therapy in TRD, continued investment in our patent portfolio, continued reduction in our expenses, having a new CEO in place by the end of March 2007, and execution of our business plan. The Company's actual decisions, performance and results may differ materially. Important factors that may cause actual results to differ include, but are not limited to: continued market acceptance of VNS Therapy and sales of the Company's product; the development and satisfactory completion of clinical trials and/or market test and/or regulatory approval of VNS Therapy for the treatment of Alzheimer's disease, anxiety, or other indications; adverse changes in coverage or reimbursement amounts by third-parties; intellectual property protection and potential infringement claims; maintaining compliance with government regulations and obtaining necessary government approvals for new applications; product liability claims and potential litigation; reliance on single suppliers and manufacturers for certain components; the accuracy of management's estimates of future expenses and sales; the results of the previously disclosed governmental inquiries; the impact of the previously announced restatement of the Company's financial statements or other actions that might be taken or required as a result of the review by the Audit Committee of the Company's Board of Directors of the Company's stock option grants, procedures, and practices, including a default under credit facilities or debt instruments; any litigation relating thereto or to the Company's stock option grants, procedures, and practices (including the previously disclosed private litigation); uncertainties associated with compliance with the requirements of the NASDAQ Panel to avoid possible delisting of the Company's stock from NASDAQ for failure to file timely periodic reports with the SEC; uncertainties associated with any appeal concerning any possible delisting by NASDAQ; uncertainties associated with stockholder litigation and other risks detailed from time to time in the Company's filings with the SEC. For a detailed discussion of these and other cautionary statements, please refer to the Company's most recent filings with the SEC, including its Form 10-K for the fiscal year ended April 28, 2006.

Proquest Identifier: 1191979581
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Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study.

Arch Neurol. 2007 Jan;64(1):103-7.

Stewart R, White LR, Xue QL, Launer LJ.

King's College London (Institute of Psychiatry), Section of Epidemiology, England. r.stewart@iop.kcl.ac.uk

BACKGROUND: The relationship between total cholesterol levels and dementia is unclear. OBJECTIVE: To compare the natural history of change in total cholesterol across 26 years between men who did and did not develop dementia 3 years after the last measurement. DESIGN, SETTING, AND PARTICIPANTS: In the Honolulu-Asia Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5 occasions between 1965 and 1993 and were screened for dementia on 2 occasions between 1991 and 1996. MAIN OUTCOME MEASURE: The slope of 26-year change in serum total cholesterol levels was estimated by a repeated-measures analysis and was compared between men with incident dementia (n = 56) and those without dementia (n = 971) at the end of the follow-up period. RESULTS: Cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period. The difference in slopes was robust to adjustment for potential confounding factors, including vascular risk factors, weight change, alcohol intake, and use of lipid-lowering agents. CONCLUSION: A decline in serum total cholesterol levels may be associated with early stages in the development of dementia.

PreMedline Identifier: 17210816

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Relation of higher folate intake to lower risk of Alzheimer disease in the elderly.

Arch Neurol. 2007 Jan;64(1):86-92.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R.

Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA. jal94@columbia.edu

BACKGROUND: Higher intake of folate and vitamins B6 (pyridoxine hydrochloride) and B12 (cyanocobalamin) may decrease the risk of Alzheimer disease (AD) through the lowering of homocysteine levels. OBJECTIVE: To relate intake of folate and vitamins B6 and B12 to AD risk. DESIGN AND PATIENTS: We followed up 965 persons 65 years or older without dementia at baseline for a mean +/- SD period of 6.1 +/- 3.3 person-years after the administration of a semiquantitative food frequency questionnaire. Total, dietary, and supplement intake of folate and vitamins B6 and B12 and kilocalorie intake were estimated from the questionnaire responses. We related energy-adjusted intake of folate and vitamins B6 and B12 to incident AD using the Cox proportional hazards regression model. MAIN OUTCOME MEASURE: Incident AD. RESULTS: We found 192 cases of incident AD. The highest quartile of total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex, education, ethnic group, the epsilon4 allele of apolipoprotein E, diabetes mellitus, hypertension, current smoking, heart disease, stroke, and vitamin B6 and B12 levels. Vitamin B6 and B12 levels were not related to the risk of AD. CONCLUSIONS: Higher folate intake may decrease the risk of AD independent of other risk factors and levels of vitamins B6 and B12. These results require confirmation with clinical trials.

PreMedline Identifier: 17210813

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Can These 'Fingerprints' Point to Alzheimer's?

Jewish Exponent. Philadelphia: Jan 4, 2007. Vol. 221, Iss. 15; pg. 36, 1 pgs

Scientists collaborating at Cornell University in Ithaca and Weill Cornell Medical College in New York City have identified a panel of 23 protein biomarkers in cerebrospinal fluid that acts as a neurochemical "fingerprint," which doctors might use someday to identify patients living with Alzheimer's disease.

The research is published in the online edition of the journal Annals of Neurology.

Right now, physicians rely on their clinical judgment to decide whether a particular patient has Alzheimer's, rather than some other form of dementia. In many cases, the diagnosis remains uncertain until brain tissue is examined at autopsy.

According to Kelvin Lee, the Samuel C. and Nancy M. Fleming Professor of Molecular and Cell Biology and associate professor of chemical and biomolecular engineering at Cornell: "Our study is the first to use sophisticated proteomic methods to hone in on a group of cerebrospinal fluid biomarkers that are specific to autopsy-proven Alzheimer's disease. Those postmortem tests confirmed that the panel is over 90 percent sensitive in identifying people with Alzheimer's disease."

Researchers at a variety of centers have long sought biomarkers in blood or cerebrospinal fluid that identify the presence of Alzheimer's pathology, and distinguish it from other conditions that cause dementia.

"Some of these studies have met with limited success, but most have correlated their findings with patient's clinical symptoms rather than working with the gold-standard of autopsyproven Alzheimer's," notes Norman Relkin, M.D., associate professor of clinical neurology and neuroscience at Weill Cornell, and director of the Memory Disorders Program at New York-Presbyterian Hospital/Weill Cornell Medical Center.

Erin Finehout, Ph.D., the lead author on the research who had been a doctoral student in Lee's laboratory, said that this has great potential to affect human health.

"Typically, Alzheimer's dis ease is not diagnosed until the disease has already caused some amount of dementia," she said. "Having a chemical test available may allow patients to be diagnosed earlier in the course of the disease."

"Just as the human genome reflects the array of genes a person possesses, the 'proteome' is the vast collection of proteins expressed by those genes," said Lee.

"Essentially, we used high-tech methods to contrast the proteomes of Alzheimer's patients against those of a control cohort that included people with other forms of dementia as well as healthy individuals, looking for key differences between the two groups."

This effort yielded intriguing results: 23 proteins that individually might not point to Alzheimer's, but together formed an identifying pattern or "fingerprint" specific to the illness.

"Although it need not have turned out that way, several of the 23 markers that emerged from this analysis proved to be proteins with known links to the pathological mechanisms of Alzheimer's disease," said Relkin.

For example, some of the biomarkers are associated with proteins that clog the brains of Alzheimer's patients. Other molecules were linked to inflammation, also a part of Alzheimer's brain pathology.

Still other proteins in the panel were linked to synaptic dysfunction - the breakdown of communication between brain cells that occurs as Alzheimer's disease progresses.

"A subsequent validation group of 10 patients with suspected Alzheimer's, and 18 healthy and demented control subjects, turned up similar results," stated Relkin.

"Based on their clinical symptoms, we found the new screen to have 93 percent sensitivity to probable cases of Alzheimer's and a 90 percent accuracy in avoiding false diagnoses," concluded Ralkin.

Despite their excitement over the new findings, the researchers stress that the results still need to be replicated in much larger populations.

Proquest Identifier: 1196391941
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The persistence of memory.

N Engl J Med. 2006 Dec 21;355(25):2697-8.

Cookson MR, Hardy J.

Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.

<<No Abstract Available>>

PreMedline Identifier: 17182998

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PET of brain amyloid and tau in mild cognitive impairment.

N Engl J Med. 2006 Dec 21;355(25):2652-63.

Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, Lavretsky H, Burggren AC, Cole GM, Vinters HV, Thompson PM, Huang SC, Satyamurthy N, Phelps ME, Barrio JR.

Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles, USA. gsmall@mednet.ucla.edu

BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles. Copyright 2006 Massachusetts Medical Society.

PreMedline Identifier: 17182990

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Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in Alzheimer's disease brain.

Brain Res. 2007 Feb 2;1131(1):187-96. Epub 2006 Dec 19.

Kumar U, Patel SC.

Faculty of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, 2146 East Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.

Among the neurotransmitter abnormalities that have been investigated in Alzheimer's disease (AD), deficits in the cholinergic system have been the most intensively studied. Another key neurotransmitter system involved with emotion and cognition is the dopaminergic system. Here we have investigated alterations in all five dopamine receptor subtypes in AD brain. Using antipeptide rabbit antibodies for each of the five dopamine receptors (D1-D5) we mapped the distribution of these receptors in postmortem AD and age-matched control brains in the frontal cortex, utilizing biotin-avidin immunocytochemistry. All five DR subtypes were expressed as cell surface and cytoplasmic proteins. Receptor-specific changes in control and AD brain were identified as follows: D4R and D3R were the predominant receptor subtypes in age-matched controls followed by D2R and D1R; D5R is the least expressed receptor subtype. In AD brain, D2R and D5R are well expressed in comparison to D1R, D3R and D4R. Expression of D1R, D3R and D4R was severely reduced in AD cortex. D2R expression is moderately reduced in the frontal cortex of AD brain. D5R is the only receptor subtype whose expression is increased in AD frontal cortex. Furthermore, in AD, we found comparable expression of D3R in astrocytes, whereas D5R-like immunoreactivity is significantly increased in astrocytes, in comparison to normal frontal cortex, where it was predominantly neuronal. These results demonstrate subtype-specific changes in dopamine receptors in AD that may be important in disease pathophysiology and that may also serve as potential targets for therapeutic intervention in AD.

PreMedline Identifier: 17182012

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