Jary Lesser

Dementia in adults with Down syndrome: Diagnostic challenges

Although dementia associated with Down syndrome is often presumed to be progressive and irreversible, variations in disease course have been described. In addition, prevalence rates have varied widely among studies. This interim report is a description of the status of 70 adults with Down syndrome who are being followed for signs of dementia. Of the 70, 12 met all criteria for dementia, 40 met subsets of criteria, and 18 met no criteria. Information is provided on instruments used, rationale for choice and revision of instruments as well as criteria used to identify dementia and changes in the status of the participants. The results suggest that extreme care is needed when diagnosing dementia in adults with Down syndrome, for both clinical and research purposes.

Aging in adults with intellectual disabilities.

A cross-sequential design was used to examine changes related to aging in adults with and without Down syndrome (ns = 55 and 75, respectively). Adults received yearly neuropsychological and medical evaluations. Support for precocious aging in adults with Down syndrome was evident only on a test of verbal fluency, with weaker support obtained on a test of fine-motor skills. Cross-sectional age differences for all adults were obtained on tests of memory and community living skills. General intellectual level, gender, and psychiatric status were consistently related to performance, indicating the need to examine such mediating variables in studies on aging.

Ritanserin in the treatment of cocaine dependence

Sixty-five cocaine-dependent subjects were enrolled into a 10-week randomized, double-blind study to determine the safety and efficacy of the serotonin-2 receptor antagonist, ritanserin (10 mg/day), in reducing cocaine consumption and craving. All subjects also participated in a structured intensive outpatient psychosocial program. Seventy-three percent of the participants completed the treatment program and follow-up. Subjects experienced a significant reduction in craving: 66.4% and 32.5% for the placebo and ritanserin groups, respectively. These reductions in craving were not paralleled by substantial decreases in cocaine use. Self-reported cocaine use was less frequent in the placebo group; paradoxically, blood levels of its metabolite, benzoylecgonine, were also higher although insignificantly so. Generally, ritanserin was well tolerated but significantly prolonged the QTc interval on the electrocardiogram. This outpatient program is effective at maintaining cocaine-dependent individuals in treatment and reducing craving. Ritanserin (10 mg/day) is not an efficacious adjunct to psychosocial treatment for cocaine dependence.

Efficacy of Phenelzine in Geriatric Depression

A low level of mood-regulating catecholamines and serotonin in the brain may be a contributing factor in clinical depression. Because the enzyme monoamine oxidase (MAO), which is responsible for the breakdown of these neurotransmitters, increases with chronological age in the human brain (Robinson et al. 1971), inhibition of MAO activity with an MAO inhibitor antidepressant (MAOI), such as phenelzine, may increase neurotransmitters and thereby alleviate depression. MAOIs may be an alternative treatment for elderly depressed patients who are unresponsive to tricyclic antidepressants or are intolerant of their anticholinergic and other side effects. severely depressed, treatment-resistant, elderly inpatients.

Assessment of orientation: relationship between informant report and direct measures.

Although informant reports of everyday functioning are often used in dementia assessments, the actual correspondence between such indirect reports of functioning and actual performance has not been examined. Orientation results on the Dementia Questionnaire for Mentally Retarded Persons were compared to those obtained in direct assessment of orientation of 138 adults with mental retardation. Fair to good agreement was found between informant report and direct assessment. However, for some orientation items, nonverbal IQ, cause of mental retardation, and age affected the level of agreement. Thus, both informant report and direct measures of orientation are necessary in dementia assessments, and further work is needed on informant scale validation.

Gender differences and the interpretation of genetic instability in Alzheimer's disease

The neuronal degeneration and death which characterize Alzheimers disease (AD) may stem from a constitutive genetic instability related to DNA repair deficits. To test this hypothesis, we treated peripheral blood lymphocytes from persons with AD, age-matched controls, and young controls with two drugs that induce chromosome breakage. Bleomycin, a radiomimetic antineoplastic drug, causes single- and double-stranded DNA breaks through the generation of activated oxygen radicals. Methyl methane-sulfonate (MMS) is a monofunctional alkylating agent that binds covalently to DNA. Cells were grown in culture for 72 h, with drug treatments for 4 h (bleomycin) or 24 h (MMS) prior to harvest. Fifty cells per subject per drug were scored for chromosome breakage. Breakage rates for both drugs in AD women were significantly higher than those in age-matched control women. This was not the case in men, due to the very high induced breakage rates seen in the age-matched normal control men. Because the induced breakage rates in AD women and AD men are equivalent, it seems likely that an independent factor may be contributing to genetic instability in the normal control men. Our findings indicate that the interpretation of the response of AD lymphocyte chromosomes to DNA-damaging chemicals can be strongly confounded by the effects of gender ratio in the control population sampled. These findings have important implications for the design of future studies of Alzheimers disease, as well as for the assessment of health risks in unaffected elderly populations.