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Clinical and Genetic Studies of Familial Presenile Dementia With Neuronal Inclusion Bodies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006176
Recruitment Status : Completed
First Posted : August 14, 2000
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system function, causing confusion, memory decline and impaired cognition (thinking ability). Patients also develop movement disorders and, possibly, seizures. Symptoms begin in midlife, between 45 and 55 years of age.

Patients with FDNIB and family members 18 years of age or older at risk for the disease may be eligible for this 3-year study.

Participants will have a medical and family history and review of medical records; interview with a medical geneticist (specialist in genetics); physical, neurological and psychiatric examinations; and the following tests and procedures:

  1. Blood tests to assess general health
  2. Chest and skull X-rays
  3. Electrocardiogram (EKG)-record of the electrical activity of the heart using electrodes placed on the chest
  4. Electroencephalogram (EEG)-record of the electrical activity of the brain using electrodes placed on the head
  5. Ultrasound of the abdomen-imaging of abdominal organs using sound waves
  6. Brain magnetic resonance imaging (MRI)-imaging of the brain using a strong magnetic field and radio waves
  7. Hearing evaluation
  8. Assessment of performance of daily living activities
  9. Single photon emission computed tomography (SPECT)-imaging of brain metabolism and blood flow using a radioactive substance injected into a vein

The evaluation will be done over a 3- to 4-day period. At their completion, participants will meet with a physician and a genetics counselor to discuss the clinically significant findings. Participants may be asked to return for follow-up evaluations every 6 months to a year (depending on the individual's condition) for 3 years.

Condition or disease
Familial Dementia With Neuroserpin Inclusion Bodies Nervous System Heredodegenerative Disorder

Detailed Description:
This project involves the study of a novel familial neurodegenerative disorder, familial encephalopathy with neuroserpin inclusion bodies (FENIB). This disorder, which has a characteristic clinical course of progressive dementia and neurologic involvement, was initially defined in one extended family. Neuroserpin is the gene for this disorder and a mutation is present in this large kindred and four additional families/cases. This protocol will characterize the clinical phenotype, delineate the natural history of the disorder and explore genotype/phenotype correlations in the index family and possibly in other reported cases. Families with immunohistopathologically-neuroserpin positive neuronal inclusions on autopsy/biopsy in an affected member(s), neuroserpin mutation-positive proband, or with familial presenile dementia with neurologic features consistent with the original FENIB family will be enrolled.

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Study Type : Observational
Enrollment : 100 participants
Official Title: Clinical, Molecular and Biochemical Characterization of Familial Encephalopathy With Neuroserpin Inclusion Bodies
Study Start Date : August 10, 2000
Actual Primary Completion Date : August 4, 2009
Actual Study Completion Date : August 4, 2009

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Patients with a family history of early-onset progressive dementia or decline in cognition and neuronal inclusion bodies which are immunohistopathologically consistent with neuroserpin inclusion bodies.

Children with progressive dementia and myoclonic epilepsy which is consistent with the reported clinical course in pediatric patients or children with the clinical phenotype who on autopsy demonstrate neuronal inclusion boidies which are immunohistopathologically consistent with neuroserpin inclusion bodies.

Family members at risk, of at least 18 years of age, including first degree relatives of affected patients and the adult offspring of these first degree relatives.

In rare instances probands and their at risk family members with known presenile dementia and a neurologic course typical of that seen in FENIB will be enrolled.

We may also enroll offsite individuals who have any of the above findings, but are too medically fragile to travel to the Clinical Center and for whom a durable power of attorney (DPA) is available. The physical examination and laboratory research studies will be performed by the Investigator(s) and all clinical studies will be done in a local accredited hospital.

Family members either not at risk and unaffected spouses may enroll primarily for genetic linkage information. These individuals will contribute a blood sample for molecular analysis only. Those unwilling to travel may also provide a blood sample only. No clinical studies will be performed on individuals from this category.


Another diagnosis of presenile demential is made by a physician including but not limited to: 1) Huntington Disease, 2) Parkinson Disease/Diffuse Lewy Body Disease, 3) Familial Alzheimer Disease with known mutations in presenilin 1, presenilin 2 or beta-amyloid precursor protein, 4) Lafora Body Disease, 5) Pick's Disease, and 6) fronto-temporal dementia.

A Durable Power of Attorney is not available in a human subject that is not medically competent to give consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006176

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)

Layout table for additonal information Identifier: NCT00006176    
Other Study ID Numbers: 000191
First Posted: August 14, 2000    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: August 4, 2009
Keywords provided by National Institutes of Health Clinical Center (CC):
Presenile Dementia
Progressive Myoclonic Epilepsy
Early Onset Progressive Dementia
Familial Presenile Dementia
familial encephalopathy with neuroserpin inclusion bodies
Heredodegenerative Disorders, Nervous System
Additional relevant MeSH terms:
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Alzheimer Disease
Heredodegenerative Disorders, Nervous System
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Genetic Diseases, Inborn
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action