Alzheimer’s Disease In Down Syndrome

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By Norberto Alvarez, MD 01ab

Overview

Alzheimer disease (AD) is the most common form of dementia. AD is a progressive degenerative disease of the brain, strongly associated with advanced age. However, it should not be considered a part of the normal aging process. AD is characterized by a relentless progression of symptoms associated with defined neuropathologic changes.

Individuals with Down syndrome (DS), or trisomy 21, develop a clinical syndrome of dementia with clinical and neuropathologic characteristics almost identical to those of AD as described in individuals without DS.

DS was recognized as a unique form of developmental disability in 1866, and few years after, in 1876, early aging was already recognized. Further publications confirm not only the premature aging and the clinical deterioration, but also the presence of the neuropathological changes of AD.

Accelerated aging in DS occurs in many other systems and is not limited to the central nervous system (CNS) alone. The recognition that DS is associated with trisomy 21 helped in the understanding of the genetic basis of this association.

The neuropathology of AD in persons with DS closely resembles that of AD in persons without DS. Autopsy studies in persons with DS showed that almost all had brain lesions meeting the criteria for AD.

Since the neuropathology typical of AD is observed very early in the life of persons with DS, the study of this condition in persons with DS could result in knowledge that could also be useful for individuals without DS.

However, because these changes are superimposed on individuals that already have a reduced brain volume, especially in the hippocampus, and other developmental abnormalities, such as reduced dendritic arborizations, decreased number of spines, spine atrophy, and abnormalities of spine orientation in pyramidal neurons, this form of AD is not an exact biologic model or a replica of the AD seen in persons without DS. Even though conclusions from research studies may be interchangeable, AD in persons with DS should be considered a different entity from AD in persons without DS.

Clinical differences have been observed, the main one being the early age of onset of AD in individuals with DS. These patients present with clinical symptoms in their late 40s or early 50s.

A recent longitudinal study in which babies born with DS were followed from age 6 weeks up to age 45 years found that the mean IQ, in verbal and nonverbal tasks, changed little between ages 21 and 45 years. In this study, tests for dementia given to persons older than 30 years showed some decline in performance from age 40-45 years.

Besides age, other studies have also shown some clinical differences that might be unique to persons with DS.

One study that compared the clinical findings in persons with dementia and DS with clinical findings in persons with dementia and intellectual disabilities due to other etiologies found that patients with DS had a higher prevalence of mood changes, over activity, auditory hallucinations, and disturbed sleep, as well as less aggression.

Temple and Konstantareas found that persons with DS and AD have less severe psychotic behaviors, fewer hallucinations, and fewer delusions and were more likely to engage in physical movements than those with AD only. In this study, 66% of the persons with AD and no DS were taking rivastigmine or donepezil, and only 26% of persons with AD and DS were on those medications. The differences observed might have been related more to the use of the medications than to the disease itself.

Because no treatment is available for the primary disease, prognosis is poor. AD is responsible for the sharp decline in survival in persons with DS older than 45 years. Only about 25% of persons with DS live more than 60 years, and most of those have AD.

To read the rest of this in depth article visit http://emedicine.medscape.com/article/1136117-overview