RESEARCH PROJECTS

Alzheimer's Disease Neuroimaging Initiative (ADNI)
Investigator-DeCarli

The major goals of the ADNI are to:

• Develop improved methods which will lead to uniform standards for acquiring longitudinal, multi-site MRI and PET data on patients with AD, MCI, and elderly controls.
• Acquire a generally accessible data repository which describes longitudinal changes in brain structure and metabolism.
In parallel, acquire clinical cognitive and biomarker data for validation of imaging surrogates.
• Develop methods which will provide maximum power to determine treatment effects in trials involving these patients.
• Test a series of hypotheses based on the clinical and biomarker data as outlined in the statistical analysis section of the protocol.

We will enroll a total of 800 subjects with 400 subjects with MCI, 200 with early AD and 200 normal controls. Subjects with MCI and controls will be followed for 3 years, those with AD for 2 years. At 6-month intervals, all subjects will be seen in person or contacted by telephone.

Subjects will undergo clinical and neuropsychological evaluations each time scanning is performed. All subjects will undergo repeated 1.5% MRI scanning (MCI-N=6 scans/subjects, Controls-N=5 scans/subject, AD-N=4 scans/subject), 25% will undergo repeated 3% MRI scanning, and 50% will undergo repeated PET scanning with the same frequency of scanning used for the 1.5% MRI imaging.

Blood and urine biomarkers will be collected at each interval when imaging data is collected from all participants. Immortalized cell lines will be established from all subjects at baseline. All subjects will be approached for LP so that a minimum of 20% and as many as 50% of the cohort will undergo a lumbar puncture at baseline and at year 1 for analysis and storage of CSF.
Currently Enrolling in Sacramento & Martinez.

Longitudinal PET: Lacunes, Cognition and Behavior
Investigator-Reed

The purpose of this research study is to better understand the biological basis for the changes in memory and thinking that can occur with aging and subcortical infarction

The data will be analyzed with respect to 3 specific aims:

• To test the hypothesis that hypometabolism of the frontal lobes is a marker for cerebrovascular pathology.
• To test the hypothesis that temporoparietal hypometabolism in the presence of lacunes is a marker for Alzheimer’s disease. 
• To test the hypothesis that strategically located lacunes are an important cause of cognitive impairment.

Thus, this study will involve studying patients using PET, MRI, and neuropsychological testing.  Only the PET protocol and neuropsychological testing is covered here.
Currently Enrolling in Martinez and Sacramento

English and Spanish Assessment of Cognition in the Elderly
Investigators-Mungas, Reed
The purpose of this project is to develop neuropsychological instruments to assess cognitive function in both English and Spanish speaking older individuals. Item response theory methods and community sampling are being used to develop and validate psychometrically matched English- and Spanish-language versions of neuropsychological tests which can be used to assess cognitive impairment and longitudinal change in cognitive function, in African Americans, Hispanics, and Caucasians.
Currently Enrolling in Martinez and Sacramento

Investigation of Capacity to Consent to Research
Investigator-Reed

We hope to learn more about making a determination as to whether or not a person has capacity to give informed consent to participate in a research study.  We are interested in learning about who makes these judgments, how much time they take, how they are related to patients’ degree of cognitive impairment and to patient diagnosis, and how practices may vary between different clinicians and sites. 
Currently Enrolling in Martinez and Sacramento

Amyloid Imaging in Aging, Cognitive Decline, and Dementia
Investigator-Reed

We will measure brain amyloid levels and glucose utilization by using a brain scanning technique called positron emission tomography (PET) that enables us to image brain function.  Brain amyloid deposition will be measured using PET with a radioactive substance [C-11]- 6-OH-BTA-1, nicknamed  “PIB” (for Pittsburgh compound B since it was invented at the University of Pittsburgh).   PIB is an experimental tracer. 

Brain glucose metabolism will be measured with a separate injection of a different radioactive substance [F-18]deoxyglucose or FDG. The PIB will be injected in a vein in your arm, and the PET scanner will be used to take pictures, following which the FDG will be injected into a vein in your arm and the PET scanner will take a separate set of pictures. The PET scans will be done at the Lawrence Berkeley National Laboratory.  The entire study can be done in one visit, although if you prefer, two separate visits, one for each scan, can be arranged.
Currently Enrolling in Martinez and Sacramento

Computer-Based Therapy For Mild Cognitive Impairment
Investigator-Reed

The purpose of this study is to determine the neuropsychological and neurophysiological impacts of a computer-based training program designed to improve the cognitive performance of patients with mild cognitive impairment (MCI).  We will conduct a small randomized, double-blind, controlled trial of this intervention with three specific aims: 1) to assess the magnitude of improvements in memory, language function, and cognitive function following training, 2) to investigate the neurophysiological mechanisms underlying such neuropsychological improvements, and 3) to demonstrate the feasibility of using this kind of computer based training therapy in older populations.

The study includes a training component, a neuropsychological assessment component, and three brain imaging components.  The training and neuropsychological assessment components are designed to replicate and extend preliminary studies that have suggested that substantial improvements in clinically relevant measures of cognitive performance can be driven in patients with MCI through the use of a standardized training paradigm (a modified version of an acoustic perceptual/language listening training program). 

The training component will be composed of a four to seven weeklong regimen of daily computer-based training sessions that subjects will pursue at home.  The neuropsychological assessment component will be composed of pre-training and post-training assessments relevant to MCI measuring memory, attention, language, and executive function abilities. 

The three brain imaging components will be composed of standardized pre-training and post-training measures of brain function that will investigate the mechanisms underlying the neuropsychological changes that occur as a result of training using positron emission tomography (PET), magnetoencephalography (MEG) and electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) studies. Some subjects who decline the PET study will be recruited to participate in the computer training and neuropsychological training sessions.
Enrollment Closed

Depression In Alzheimer's Disease
Investigator-Reed

The purpose of this research is to collect clinical information about people with alzheimer's disease and their moods using questionnaires. The research is looking at how an AD patient's mood affects his/her thinking and ability to perform everyday activities. This information will be entered into a database for future uses in determining if people who have Alzheimer's disease are depressed.
Enrollment Closed

Effectiveness Of Routine Clinical Treatment For AD and Related Problems (MIRECC)
Investigator-Reed, Mungas & DeCarli

Research Plan Overall Objective: 

Our work will cover the spectrum from human neurobiology and clinical efficacy studies, to health services research.  Prominent investigators in the field of dementia in Palo Alto will lead the dementia program.  Building upon a working research structure already existing in four of the six VISN facilities, these investigators will complete a VISN-wide structure for the evaluation of predictors of response and the effectiveness in “real world” situations of treatments of both cognitive and behavioral symptoms in dementia.  Similarly, the PTSD research program will be led by seasoned investigators in San Francisco who will extend a research structure, already working effectively in several facilities, to other VISN facilities.

Educational Plan Overall Objective: 

Our education plan is designed to disseminate current state-of-the-art knowledge as well as new information yielded from MIRECC research investigations specific to the care of two groups of veterans: (1) those with PTSD and (2) those with behavioral, cognitive, or functional problems associated with dementia.
Enrollment Closed

Ethnic And Gender Influences On Help-Seeking In Dementia
Investigator-Hinton

Aim 1:To examine the impact of ethnicity (i.e. Mexican American Versus White non-Hispanic) and gender on spousal caregiver explanatory models (i.e. problem definition, attributions, and perceived seriousness), help-seeking behaviors, and treatment preferences for dementia neuropsychiatric symptoms.

Aim 2: To systematically compare spousal caregiver perspectives (i.e. accounts of help-seeking, explanatory models, and treatment preferences related to dementia neuropsychiatric symptoms) with those of the primary care clinician who is caring for the dementia-affected elderly.
Enrollment Closed

Heterogeneity of Mild Cognitive Impairment (MCI)
Investigator-DeCarli

Evidence suggests that significant memory impairment, short of dementia and often denoted as mild cognitive impairment (MCI) in the elderly may be a transition phase between the normal again process and AD. Individual trajectories of cognitive decline can be quite variable, however, and not all older individuals with cognitive impairment have memory loss as the predominant symptom suggesting considerable clinical and etiological heterogeneity.

In addition, since CVD is common to an aging population and potentially treatable, understanding the role CVD plays in the expression of MCI and progression to dementia could also result in clinical therapeutic trials aimed at the prevention of cerebrovascular-related cognitive impairment. The prevalence and impact of CVD on the natural history, patterns of cognitive performance or longitudinal cognitive changes in MCI are currently unknown.

To address this gap in current understanding, this project will examine the clinical and neurobiological substrate of MCI in a large group of MCI patients selected to have both memory and non-memory cognitive impairments as well as a broad spectrum of CVD severity.
Currently Enrolling in Martinez and Sacramento

Relationship Between CSF Cortisol And APOE Genotype
Investigator-DeCarli

The overall aim of this study is to see if there is a relationship among high levels of the stress hormone cortisol, the type of Apolipoprotein E (APOE) gene a person carries, and decline in memory and other brain functions. Cortisol plays a role in the body's response to physical and mental stress. We believe that if this hormone is overactive, it may worsen the changes in memory and other brain functions that result from normal aging and Alzheimer’s disease.
Enrollment Closed

The Measurement and Prediction of Everyday Function in Dementia
Investigator-Farias

The principle aim of this project is to gain a better understanding of everyday function, both in terms of how to define and measure this construct as it pertains to older adults, as well as to identify its neuropsychological correlates.

These relationships will be examined in the context of the classification system set forth by the World Health Organization (WHO), which describes the consequence of disease at three levels: impairment, disability, and handicap. According to this model, the consequence of disease can be hierarchically arranged wherein ‘impairments’ (discrete changes in specific areas of cognition or everyday function) are precursors to ‘disability’ (changes in activities of daily living, ADLs), which in turn is a precursor to ‘handicap’ (the social consequence of disease).

Previous research on the functional decline in dementia has focused primarily on changes at the level of disability and therefore has been limited in the assessment of early, mild functional changes. In this project we widen the scope of functional assessment to include all three levels of functional change, with a particular emphasis on the assessment of change at the level of ‘impairment’ in an effort to better capture subtle declines in function. We further propose that functional impairment can be organized into domains that have demonstrable neuropsychological relevance: memory, language, visual-spatial abilities, and executive functions.
Currently Enrolling in Martinez and Sacramento

Blood Genomics of Abnormal White Matter Hyperintensities
Investigator-DeCarli
This study examines gene expression profiles of adult patients with dementia, stroke and normal cognition. The study involves obtaining a blood sample, isolating RNA, and examining the expression of the RNAs on Affymetrix microarrays. Subjects includes those with normal white matter, abnormal amounts of WM and dementia patients. RNA profiles from these individuals will be compared to cognitively normal individuals with various degrees of abnormal white matter signal detected on MRI. A third group of individuals with cognitive impairment not meeting criteria for dementia will also be included.

Specific Aims:

1. Blood genomic profiles will be obtained in patients with cognitive impairment and abnormal white matter signals seen on MRI and patients with normal white matter signals seen on MRI. We propose that the blood genomic responses in patients with dementia with normal white matter signals will differ from those dementia patients with abnormal white matter signals. Assuming that this is the case these findings will form the basis for developing blood tests that might differentiate the two forms of dementia and serve as a basis for different treatment
2. Blood genomic profiles will be obtained in patients with normal cognition and abnormal white matter signals seen on MRI and subjects with normal white matter signals seen on MRI. We propose that the blood genomic responses in subjects with normal white matter signals will differ from those subjects with abnormal white matter signals. Assuming that this is the case, these findings will form the basis for identifying genetic influences that might put older individuals at risk for later-life dementia.

UCD ADC CSF Tissue Bank
Investigator-DeCarli
this is a non-randomized natural history non-treatment study involving the UCD Alzheimer's Disease Research Ctr. the study aims to recruit a total of 80 subjects consisting of approximately 20 normal controls, 20 individuals with mild cognitive impairment 9McI), and 40 subjects with dementia. Specific Aims

1. The aim of this study is to establish a bank of CSF and plasma samples for future determination of potential biomarkers for Alzheimer's disease, as well as other
2. neurodegenerative/neuropsychiatric diseases. CSF obtained through lumbar puncture described below will be aliquoted and stored in the UCD ADC CSF/plasma bank. This resource will be made available to Alzheimer's disease research investigators nationally and internationally by request and approval of the UCD ADC Executive Committee, which consists of the ADC Core leaders and other administrative personnel.

ERPs as Markers of Early AD Across Ethnic Groups in MCI
Investigator-John Olichney, MD

Aims: 
1) To test the sensitivity and predictive value of abnormal ERP word repetition effects in patients with MCI.  We will test the predictive value of ERP word repetition effects across all MCI patients, and within subgroups of interest (e.g. minority MCI and non-amnestic MCI). We predict that reduced ERP word repetition effects will be associated with subsequent conversion to AD across and within all these subgroups.          

2) To test how well preclinical abnormalities of the P600 and N400 word repetition effects predict subsequent decline in the cognitive domains of memory and language, respectively.  Prior work suggests that the loss of the P600 word repetition effect indicates dysfunction of neural circuits critical for explicit/declarative memory, while N400 repetition effects appear to reflect implicit memory processes which are related to semantic priming and language comprehension. (Olichney et al Brain 2000).

This study will test a few compounds for their effects in reducing the amount of aggregates of amyloid-b protein (Ab) in the brain. Ab is the major protein component of the amyloid plaques in the brains of patients with Alzheimer's disease (AD).

Ab also exists in small aggregates that are present in early stages of the disease, either inside or outside the neurons in the brain. Many lines of studies strongly support the toxic effects of various Ab aggregates, which may cause dementia in AD. Methods to reduce the levels of Ab, prevent Ab aggregation or eliminate existing Ab aggregates have been proposed for AD therapies. In this proposal, we focus on discovering small molecule, "drug-like" compounds targeting those small Ab aggregates (oligomers) inside the neurons, which have been shown to be an early lesion and causally related to some cognitive deficits and neurodegeneration in AD animal models.

This group of compounds comes from well characterized amyloid ligands, originally developed for use as specific tracers for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging of brain amyloid. The wish is that these compounds will locate and interact with the small Ab aggregates in the brain and somehow eliminate them. We have some evidence in the test tubes and cultured cells that this might work in living beings. Since animal experiments are a necessary step toward finding effective compounds, we will subject a new and robust AD transgenic model called 5XFAD mice to various regimens of treatments with the candidate compounds.

We will examine whether the compounds are able to reduce the levels of neuronal Ab deposits, and by doing so, ameliorate the synaptic and neuronal loss which are features similar to AD. The proposed experiments would help us to understand the causal relationship of various lesions in the brain of AD patients, and therefore might reveal the fundamental cause of AD. They would also help us to validate or reject our candidate compounds that may have a potential in reducing an early neurotoxic event in AD.

FTLD is one of the most common presenile neurodegenerative diseases, representing around 15% of early-onset dementia cases (Ikeda). However, diagnostic accuracy is well below what has been achieved for AD, and misdiagnosis is common even at centers specializing in dementia.  Current diagnostic criteria have been criticized for being cumbersome and difficult to use, not designed for use by non-specialists, low inter-rater reliability, and an unacceptably high rate of misdiagnoses. 

To address these concerns, international groups of experts have convened to develop new, empirically-based criteria that reflect the recent major advances in our understanding of this group of diseases.  The purpose of this three-year consortium application is to test the inter-rater reliability and validity of these new criteria and develop training modules that will efficiently translate this knowledge to the state ARCCs and to community health care providers. 

The following specific aims will be addressed:

Specific Aim 1:   Assess the inter-rater reliability of the new FTLD diagnostic criteria

Specific Aim 2:   Assess the validity of the new FTLD diagnostic criteria by collecting pathologically-confirmed cases of FTLD and AD and retrospectively applying the diagnostic criteria 

Specific Aim 3:  Assess the validity of the new FTLD diagnostic criteria by prospectively following new cases of FTLD diagnosed with the new criteria.  Subjects will be studies with PIB and, in some instances, pathological confirmation of diagnosis will be possible. 

Specific Aim 4:   To develop educational materials for translate these improved diagnostic criteria to other ARCCs and to community health care providers.

1. 1. MRI studies of offspring of the original Framingham cohort in an effort to define risk factors for dementia and relate these to cognition
2. 2. MRI studies of the NHLBI twin cohort in order to examine heritability of brain morphology in a cross sectional and longitudinal fashion
3. 3. The use of MRI as an outcome measure indicative of cerebrovascular disease in the Framingham cohort and the offspring of this cohort
4. 4. The use of MRI as a measure of brain changes associated with AD and cerebrovascular disease in a biracial cohort in order to define the relative contribution of cerebrovascular disease to dementia
5. 5. The use of MRI to evaluate brain structure in normal aging and incipient AD in the Framingham cohort
6. 6. In a pending study, Dr. DeCarli will use MRI as a phenotypic measure in a quantitative trait design as part of the MIRAGE study.
   Not Enrolling
   

Subjective Experience of Mild Cognitive Impairment
Investigator-Kumari

Mild Cognitive Impairment (MCI) has been recently identified as a clinical entity that has the probability of progressing on to dementia. The goals of this pilot, qualitative study is relatively modest: to elucidate how people with MCI understand their diagnosis; to identify discrepancies between the patient's and professional views; to describe the impact of the diagnosis of MCI on a person's view of themselves and their relationships with others; and, to understand how they cope with the impairment. this research is important because identifying areas of misunderstanding between lay and professional perspectives can lead to improved communication and rapport between patients, their families and health care professionals, and enhance early diagnosis and better management.
Currently Enrolling in Sacramento only

Sacramento Area Latino Study on Aging (SALSA)
Investigators-Haan, Mungas, Jagust
This project is an epidemiological study of functional impairment and dementia in older Latinos. This is a longitudinal cohort study of approximately 1800 Latinos 60 years of age and older. It is examining prevalence and risk factors for dementia in this population as well as incidence of dementia and predictors of cognitive decline. An imaging substudy obtained MRI and PET scans from a subsample of SALSA participants to examine imaging correlates of cognitive decline and impairment
Enrollment Closed

The Cortical Substrates and Functional Properties of Human Recognition Memory
Investigator-Yonelinas
The aim of the current proposal is to test the hypothesis that the recollection deficits seen in normal aging are related to changes in white matter as indexed by WMHs. By measuring recollection and familiarity-based recognition in a group of aged subjects with a range of WMH loads, we will determine if recollection is related to white matter abnormalities.

The long term goal of this line of research is to understand the cognitive functions and brain mechanisms that are critical for encoding and retrieval of long term memory. If we can demonstrate a link between WMH and recollection, them future studies will be designed to further characterize the specific cognitive functions that contribute to normal recollection and familiarity-based recognition responses in aging.
Currently Enrolling in Martinez and Sacramento

The Role of Lipoprotein Oxidation in Alzheimer's Disease
Investigator-Bergt

Lipoproteins play a crucial role in brain cholesterol homeostasis, most likely through their ability to accept cellular cholesterol, the first step in reverse cholesterol transport. We are testing the hypothesis that microglia-derived oxidative stress alters lipoprotein regulated cholesterol homeostasis in the brain and contributes to Alzheimer's pathology. Our specific aims are:

1. to detect and characterize microglia-derived oxidation products in cerebrospinal fluid (CSF) lipoproteins in Alzheimer's patients using mass spectrometry and immunological methods.
2. to investigate the effect of oxidized CSF lipoproteins on cholesterol efflux. we will compare the efficacy of CSF from Alzheimer's Patients and controls for accepting cholesterol form cells.

This study will provide important insights into the role of lipoprotein oxidation on cholesterol homeostasis in the brain and its effects on amyloid plaque formation. These studies will have implications for the biological significance of oxidative reactions in Alzheimer's disease and other inflammatory diseases.
Enrollment Closed

 
Ginkgo Study
Investigators-DeKosky, Robbins, DeCarli
CHS is also serving as the focus for the ginkgo primary prevention trial. The purpose of this study is to determine if ginkgo biloba is effective in preventing new-onset dementia and Alzheimer’s disease.
Enrollment Closed

Semantic Memory in Alzheimer’s Disease
Investigator-Ober
Dr. Ober’s studies are oriented towards understanding how semantic knowledge is disrupted in AD, thus providing a model of semantic function that can illuminate normal semantic function. Her current project will attempt to define which aspects of semantic memory structure are impaired in AD, by examining a variety of factors related to both the task and neuropsychological factors. In addition, a subgroup of subjects will have MRI scans in order to relate regional brain atrophy to loss of various aspects of semantic memory.
Currently Enrolling in Martinez and Sacramento

Alzheimer's Disease and Postprandial Vascular Inflammation
Investigator-Rutledge
We hope to learn more about how the foods we eat could affect inflammation in our blood vessels. The purpose of this study is to see what effects (good and bad) a moderately high-fat meal has on inflammation in our blood vessels.
Currently Enrolling in Martinez and Sacramento

White Matter Disease Effects on Cognitive Aging, Part I: Development of Tasks.
Investigator-Mayda
The purpose of the research is to study how cerebrovascular disease (e.g. stroke) affects memory and thinking in older people and to develop these tasks for part II of the study.
Currently Enrolling in Martinez and Sacramento

Hemispheric Collaboration in Normal and Abnormal Aging
Investigator-Baynes
The purpose of this research project is to study how changes take place during communication between the two brain hemispheres in the normal aging brain and/or a brain with Alzheimer's Disease.
Currently Enrolling in Martinez and Sacramento

Trial Of Simvastatin To Slow The Progress Of Alzheimer's Disease
Investigator-Clinical Trials

In earlier studies in animals and humans, researchers found that lowering cholesterol levels with statins seems to have a positive impact on brain function and reduces the risk of AD. The CLASP trial will test the link between using a cholesterol lowering medication and slowing disease progress in people with mild to moderate Alzheimer's disease (AD).

CLASP is a research study to investigate the safety and effectiveness of simvastatin (a cholesterol lowering drug or statin) to slow the progression of AD. The clinical trial will include the treatment of patients with mild to moderate AD, and the objective is to evaluate the safety and efficacy of simvastatin to slow the progression of AD, as measured by the cognitive portion of the AD Assessment Scale. Measures of clinical global change (ADCS-CGIC), mental status, functional ability, behavioral disturbances, quality of life and economic indicators will be made also.

The study design is randomized, double-blind, placebo-controlled, parallel group design with equal randomization to drug and placebo. Randomization will be stratified and blocked to ensure balanced assignment within site. Sample size will include 400 participants enrolled from approximately 40 sites with a goal of 10 to 15 volunteers enrolled at each site. Study medication will be as follows: 20 mg of simvastatin or matching placebo to be given for 6 weeks, followed by 40 mg of simvastatin or matching placebo for the remainder of the 18-month study period. Participants will be instructed to take the medication once a day in the evening. Safety parameters to be checked will include adverse events, symptom checklists, vital signs, physical and neurological examinations, and laboratory tests.
Enrollment Closed

Study of High Dose Supplements to Reduce Homocysteine and Slow the Rate of Cognitive Decline in Alzheimer's Disease
Investigators-Clinical Trials

Blood levels of homocysteine are elevated in Alzheimer's disease (AD), and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Homocysteine levels can be reduced by administration of high dose supplements of folate and vitamins B6 and B 12

This is a multicenter, randomized, controlled clinical trial to determine whether reduction of homocysteine levels with high dose folate/B6/D12 supplementation will slow the rate of cognitive decline in subjects with AD. It is a parallel design study, including two groups of unequal size. The primary outcome measure is the longitudinal decline in the ADAScog.
Enrollment Closed

Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Immunogenicity Trial of AAB-001n
Investigator-Clinical Trials

This is a Phase IIa, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose, safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity trial of AAB-001, a monoclonal antibody infusion, in persons with mild to moderate Alzheimer’s disease sponsored by Élan Pharmaceuticals, Inc.  

The primary objective of this study is to evaluate the safety and tolerability of AAB-001given multiple times to patients with mild to moderate AD. The clinical hypothesis is that treatment with multiple doses of AAB-001 in patients with mild to moderate AD is safe and well tolerated.
Currently Enrolling in Sacramento only

Primary Prevention Trials
Investigator-Clinical Trials

Over the past 10 years, the Alzheimer’s Disease Cooperative Study group (ADCS) Instrument Committee has helped to define the state of the art in assessment for Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) clinical trials.  In so doing, the ADCS has recognized that in addition to traditional patient efficacy measures, development of AD treatments must address the broader social and economic value of any interventions.  Further work is now needed to improve the efficiency and reduce the cost of measures used in AD primary prevention trials.  Given the pharmacological, scientific and clinical expertise of the ADCS, we are in a unique position to define the appropriate domains, measures, and data acquisition methods for assessing the clinical impact and cost effectiveness of treatments designed to prevent AD.

Pilot Collaborative PET Imaging Trial
Investigators-Clinical Trials

A recently completed retrospective study of pathologically confirmed cases suggested that positron emission tomography with FDG-PET could augment clinical evaluation and is particularly valuable in differentiating FTD from Alzheimer's disease (AD). this is a 3-year in a prospective multi-center pilot clinical trial to confirm and expand upon these findings and determine the value of FDG-PET in the initial evaluation of patients with symptoms suggesting FTD.

Aim 1: Replicate in prospective population the findings of the previous retrospective study showing that FDG-PET has better accuracy in distinguishing FTD from AD than clinical history and examination.

Aim 2: Compare the accuracy of diagnosis of FTD, AD, and psychiatric illness before and after FDG-PET with the final diagnosis of a consensus panel based upon all clinical data collected over 18 months of observation.

Aim 3:Compare physician diagnostic confidence, proposed patient management, and caregiver satisfaction before and after FDG-PET imaging during the initial evaluation of patients with cognitive impairment and prominent behavioral or language symptoms

Aim 4: Develop and evaluate the infrastructure necessary for the conduct of a large, multi-center prospective study of FDG-PET as a diagnostic biomarker for FTD.
Enrollment Closed

Texas SW Homocysteine
Investigators-Clinical Trials

Many people with AD do not have enough vitamin B12 and folic acid in the body. Not having enough B12 and folic acid can cause high blood levels of homocysteine. Having too much homocysteine in the body can lead to heart and blood vessel disease. New research suggest that too much homocysteine in the blood may also lead to AD

It is possible that lowering homocysteine levels may decrease the risk of having AD. The purpose of this study is to investigate tow things: (1) the relationship between blood levels of homocysteine and AD and (2) the effect of vitamin therapy on lowering bolood homocysteine levels.
Enrollment Closed

Whether Natural Huperzine A Improves Cognitive Function
Investigator-Clinical Trials

The purpose of the study is to evaluate the safety and efficacy of huperzine A 200µg bid and huperzine 400µg bid in patients with AD and to determine the relationship between blood cholinesterase activity and cognitive function in AD patients treated with huperzine A.  

Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use. In fact, it is the primary treatment used in China for the treatment of Alzheimer’s Disease (AD) where it is used in a dose of 200µg bid. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for AD.

The drug is currently available as a nutriceutical in this country, and is being used by some U.S. clinicians to treat AD.  Phase I clinical trials in the US indicate that huperzine A was well tolerated. At the 200µg bid dose there were mild GI symptoms, fatigue and drowsiness. At the 400 µg bid dose there was dry mouth, bradycardia, headache and muscle cramps. There have been no controlled clinical trials outside China assessing its toxicity and efficacy. Because huperzine A is a natural product, it is not patentable and thus, if effective, could be a less expensive source of anticholinesterase medication than those currently available.