Plenary Session on Mental Health

Alzheimer's Disease (AD) in Adults with Down Syndrome
Speakers: Wayne Silverman, Ph.D. and Warren Zigman, Ph.D., NYS Institute for Basic Research
Nicole Schupf, Ph.D.,Taub Inst. of Columbia University, Tiina Urv, Ph.D., Shriver Center, U. Mass. Med. Sch.

Virtually all adults with Down syndrome develop some of the key neuropathological features of Alzheimer's disease by their late 30s, yet only a minority experience frank dementia. Even among those affected individuals, age at onset (or age at diagnosis) varies widely, as does rate of progression. Obviously, factors in addition to the presence of an extra copy of chromosome 21 (the underlying cause of Down syndrome) and its associated triplication of the gene coding for amyloid precursor protein must be responsible for these individual differences. Four presentations will address this issue and describe current findings of our ongoing prospective and longitudinal studies of 331 adults with Down syndrome ranging from 45 to over 70 years of age.

(1) Risk Factors for Alzheimer's Disease in Adults with Down Syndrome: Homeostatic Factors
Individual differences in risk for Alzheimer's disease among adults with Down syndrome will be related to seizure history, premorbid depression, cholesterol levels, and history of thyroid dysfunction, putative risk factors suggested by previous studies of the general aging population. Given the atypical aging of adults with Down syndrome, our studies are clarifying the influences of these factors on vulnerability within this specific population.

(2) Biomarkers of risk for Alzheimer's disease in adults with Down syndrome
The roles of apolipoprotein E genotype, plasma amyloid beta peptides, estrogen-related hormones, and nonsteroidal anti-inflammatory agents in influencing risk for Alzheimer's disease will be explained for adults with Down syndrome. Because biomarkers can be related to underlying mechanisms of pathogenesis, their identification can provide insights into potential strategies for delaying or preventing onset of disease as well as indications of individuals at higher risk.

(3) Patterns of Maladaptive Behavior in Adults with Down Syndrome and Dementia
Alzheimers disease has become a significant health concern among adults with Down syndrome and it is important to develop a thorough understanding of the progression of symptoms. Most previous studies dealing directly with dementia in adults with Down syndrome have focused on cognitive and adaptive declines, but the emergence of psychiatric conditions and problem behaviors can be of major clinical significance. This presentation will describe our new findings relevant to changes in maladaptive behaviors as dementia progresses.

(4) Individual Differences in Rate of Progression of Symptoms among Adults with Down Syndrome and Dementia
Changes in status of individuals with Down syndrome will be described, synchronized with either onset of their symptoms of dementia or their time of first diagnosis of Alzheimer's disease (AD). Survival analyses will be used to examine life expectancy once dementia is recognized, as well as the likelihood that, within specific time intervals, affected adults experience substantial declines in mental status or overall adaptive competence. Anecdotal reports suggest that the rate of progression of Alzheimer's disease is often greatly accelerated in adults with Down syndrome once symptoms begin, and this issue will be discussed explicitly.