The Evaluation and Follow-up of Individuals With Memory Disorder
Condition: Alzheimer's Disease; Dementia; Healthy; Memory Disorder
MeSH terms: Alzheimer Disease; Dementia; Memory Disorders
Study type: Observational

Summary: 
      The purpose of this study is to evaluate people with mild memory problems, those with
      dementia, those at risk for developing Alzheimer's disease (AD), and healthy volunteers to
      identify markers of AD before the changes that occur with the disease begin.

      The origin and markers of progression for Alzheimer's disease (AD) are relatively obscure.
      Despite increased understanding of the underlying biology of AD, its clinical diagnosis is
      still made only after progressive cognitive decline; definitive diagnosis is confirmed at
      autopsy. This study will examine biomarker changes over time in a distinct cohort of people
      with an increased risk of developing AD. The study will also identify and track biological
      changes that occur with progressive dementia and compare those changes to the known cognitive
      and emotional disturbances that characterize AD.

      Individuals with a first-degree relative with AD will be recruited into an at-risk cohort.
      They will be followed and compared to a group of healthy volunteers for a minimum of 8 years.
    

Detailed description: 
      The temporal origin of Alzheimer's disease (AD) and markers of progression of this disease
      process are relatively obscure. Despite outstanding advances in the understanding of the
      underlying biology of AD, the clinical diagnosis is still made by consensus following
      progressive cognitive deterioration and confirmed only at autopsy. The protocol will serve
      two functions. First, we will evaluate and longitudinally follow a cohort of first-degree
      relatives of AD subjects who are currently normal but are at increased risk of developing AD
      sometime in the future. This cohort will be compared to a group of normal controls along
      multiple behavioral, cognitive, motor function, genetic and biologic parameters over a period
      of years. While differential rates of conversion to AD might eventually be expected based on
      family history and other fixed variables (i.e., APO E status), this study is not powered to
      simply be a study of conversion to AD. Rather, it is a study of biomarker change over time in
      a distinct cohort of people with increased risk of developing AD. Conversion to a clinical
      diagnosis of AD is only one of the variables; others will include cognitive testing,
      neuroimaging, genetic markers, assessment of functional capacities and cerebrospinal fluid
      (CSF) measures that may ultimately function as disease surrogates. As part of this at risk
      cohort, we will recruit and longitudinally follow a series of pre-symptomatic and symptomatic
      subjects with known genetic mutations (presenilin 1, presenilin 2, or APP). Second, we will
      follow a large cohort of dementia subjects themselves for whom the diagnosis is either AD or
      some other related dementia. The purpose of this second part of the follow-up study is to
      identify and track those biologic changes that occur with progressive illness and,
      furthermore, to relate those changes to the known cognitive and emotional disturbances which
      characterize AD.

      By longitudinally following separate cohorts of normal controls without a family history of
      AD, normal controls with a family history of AD, subjects with mild cognitive impairments and
      diagnosed dementia subjects, we hope to track the spectrum of AD from its clinical and
      biologic origins. As a result, this study is both a diagnostic screening protocol and a
      natural history protocol. It will address a series of important clinical and biological
      questions among a wide range of normal and diseased individuals and should serve as a basis
      for the development of biologic markers in AD that could be used for diagnostic and
      therapeutic purposes in the future. A long-term goal of this protocol to identify markers and
      eventually individual people who are at increased risk of developing AD before the typical
      cognitive changes of AD become manifest. In pursuit of that goal, we will also carefully
      monitor and evaluate the clinical medications taken by our subjects to see if they influence
      the course of AD.
    

Keywords: Dementia; Alzheimer's Disease; Cerebrospinal Fluid; Diagnostic Test; Cognitive Testing; Memory Disorder; Normal Volunteer