7-25-16 Down Syndrome Dementia

© 2016           

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background: We had a patient who had a son with Down Syndrome (Trisomy 21 – three copies of chromosomes 21 instead of the expected two copies) who as an adult was able to live in an assisted living apartment on his own, and ride the bus to work.

With the wonderful medical advancements with care and treatment of Down Syndrome he lived a fairly independent life until his early 50’s.

His mother became concerned because he started to be late for work, missed his bus or forgot where to catch the bus and what stop to get off at and even got lost some nights coming home.

The mother decided to have him evaluated and the eventual diagnosis was not complications of Down Syndrome but rather “aging issues” that are faced by individuals without a chromosomal problem but further complicated by the diagnosis of Trisomy 21 (Down Syndrome).

The final diagnosis was Down Syndrome Dementia.       

Dementia: A chronic or persistent disorder of the mental processes caused by brain disease or injury or marked by memory disorder, personality change or impaired reasoning.

Analysis: Dementia can be seen in individuals with Trisomy 21 (Down Syndrome) and the changes in the brain are similar to those seen in other individuals with Alzheimer’s Disease e.g. neurofibrillary tangles, amyloid deposits, amyloid vessel changes and other brain plaques.

Other organ systems can show premature aging changes in addition to the brain and these changes may be seen in individuals with Down Syndrome as early as the 30’s or 40’s.

However, because these changes are seen in individuals with Down Syndrome who have other developmental and physical changes the manifestations may be less recognizable.

The premature aging and decline in brain function is believed to be responsible for the accelerated decline seen in individuals with Down Syndrome, particularly after age 40-45 years and the subsequent recognition of progressive dementia.

Although the brain changes seen in patients with Alzheimer’s Disease who have a normal chromosome complement and patients with Down Syndrome and dementia are similar, the manifestation of dementia in individuals with Down Syndrome are seen as a slightly different entity.

To date, no definite intervention with medication has been shown to significantly delay or reverse the progression of the disease although some medications may help with symptoms such as hallucinations, psychotic episodes or abnormal movements.

The Amyloid Precursor Protein (APP) is located on chromosome #21q21.3. Down Syndrome individuals have three copies of chromosome #21.

Amyloid beta and the protein tau are believed responsible for the formation of the neural tangles seen in the brains of Alzheimer’s patients and adults with Down Syndrome.

High levels of the gene DYRK1A also on chromosome 21 (21q22) increases protein tau levels and APP levels. The gene PICALM on chromosome 11q14 and APOe on chromosome 19q13.2 are also believed to increase the risk for Alzheimer’s Syndrome and dementia in individuals with Down Syndrome.