BENEFIT FROM EXERCISE AND CAREGIVER TRAINING SHOWN IN ALZHEIMER’S DISEASE

A new study, published in the October 15 JAMA, demonstrated that a regular exercise program combined with caregiver education and training on supervising exercise improved the physical and emotional health of individuals with moderate to severe Alzheimer’s disease. Linda Teri, PhD, of the University of Washington School of Nursing and Group Health Cooperative’s Center for Health Studies, Seattle, and colleagues conducted a randomized controlled trial that included 153 community-dwelling patients with Alzheimer’s disease to determine whether a home-based exercise program for patients with Alzheimer’s disease combined with teaching caregivers how to manage behavioral problems would help decrease the frailty and behavioral impairment that are often prevalent in Alzheimer’s disease and that can lead to increased functional disability and institutionalization. The program’s goal was to have the people with Alzheimer’s disease exercise moderately for 30 minutes a day.

At three months, in comparison with the routine care patients, more patients in the combined exercise and caregiver training program, known as Reducing Disability in Alzheimer Disease (RDAD), group exercised at least 60 minutes per week and had fewer days of restricted activity. Patients in the RDAD group also had improved scores for physical role functioning compared with worse scores for those in the routine medical care group. People in the RDAD disease group had improved scores on the Cornell Depression Scale for Depression in Dementia while the routine medical care group had worse scores.

At two years, people in the RDAD group continued to have better physical role functioning scores than did those in the routine medical care group and showed a trend for less institutionalization due to behavioral disturbance. For study participants with higher depression scores at baseline, those in the RDAD disease group improved significantly more at three months on the Hamilton Depression Rating Scale and maintained that improvement at 24 months. The authors suggested that caregivers may also have experienced improved physical health and well-being, though caregiver benefits were not formally measured as part of the study.

“Through programs of exercise and caregiver training, such as the one demonstrated in this study, people with Alzheimer’s disease may be able to maintain their physical health and share more positive interactions with their caregivers. That is potentially a big quality-of-life improvement for patients, caregivers, and family members,” said Cornelia Beck, PhD, RN, of the Alzheimer’s Association Medical and Scientific Advisory Council. “The fact that the effects persisted at 24 months is especially encouraging,” she added.

Suggested Reading
Teri L, Gibbons LE, McCurry SM, et al. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003;290;2015-2021.

ANTIBODY DETECTION COULD IDENTIFY THOSE MS PATIENTS WHO DO NOT RESPOND TO TREATMENT

The detection of antibodies to interferon ß in patients with relapsing-remitting multiple sclerosis (MS) could be important in identifying patients who do not respond well to interferon ß therapy, according to Danish researchers. Their findings could have implications for the provision of alternative drug therapies, they suggested in the October 11 Lancet.

In a study designed to assess the clinical effect of neutralizing antibodies in patients with relapsing-remitting MS who were receiving interferon ß therapy, the Danish Multiple Sclerosis Study Group measured these antibodies every 12 months for up to 60 months in 541 randomly selected patients, using antiviral neutralization bioassays of differing sensitivities. Clinical data were collected prospectively at follow-up visits at three and six months. These included neurologic examination with Expanded Disability Status Score and recording of relapses and adverse effects, as well as standard laboratory tests. Blood samples for measurement of neutralizing antibodies against interferon ß were collected at baseline, three, six, 12, 18, 24, 36, 48, and 60 months of treatment; only the annual results were used in the study, the researchers noted.

The investigators found that the patients developed neutralizing antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods than they were during antibody-negative periods, they noted. When comparing the number of relapses in antibody-positive versus antibody-negative periods, the researchers found odds ratios of 1.51 to 1.58. Additionally, the time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months.

“Our findings suggest that the presence of neutralizing antibodies against interferon ß reduces the clinical effect of the drug,” the researchers wrote. “In patients who are not doing well on interferon ß, the presence of antibodies should prompt consideration about change of treatment,” they added, though they recommended that such changes still be based primarily on clinical outcomes. While long-term clinical studies are needed to clarify the correlation between neutralizing antibodies to interferon ß and disease progression, the investigators nonetheless concluded that these antibodies should be monitored routinely, at least in patients with clinical activity.

Suggested Reading
Sorensen PS, Ross C, Clemmesen KM, et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet. 2003;362:1184-1191.

MILD CONGITIVE IMPAIRMENT WORSE THAN EXPECTED IN SENIORS

The rate of mild cognitive impairment in persons 75 and older is higher than expected, affecting 22% of those in the age-group, according to two articles by University of Pittsburgh researchers published in the October Archives of Neurology. Oscar L. Lopez, MD, and colleagues examined 3,608 patients who underwent detailed neurologic, neuropsychological, MRI, and psychiatric testing to identify dementia and mild cognitive impairment. The study cohort was drawn from participants in the Cardiovascular Health Study Cognition Study, an ancillary study of a larger epidemiologic study begun in 1987.

In the first part of the Cognition Study, the investigators determined the prevalence of mild cognitive impairment to be 19% in participants younger than 75; prevalence increased to 29% in participants older than 85. Mild cognitive impairment of an “amnesiac-type” was less frequent than mild cognitive impairment of a “multiple cognitive deficits–type,” they reported.

In the second part of the study, Dr. Lopez, Associate Professor of Neurology at the University of Pittsburgh, and colleagues investigated the risk factors for mild cognitive impairment. They found that mild cognitive impairment was associated with African-American race, low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, apolipoprotein E epsilon4 allele, and measurements of depression.

“We were surprised at how prevalent the condition was and how other medical conditions increased people’s risk to have mild cognitive impairment,” Dr. Lopez said. “This emphasizes the importance of good medical care in preventing the development of brain disease.”

Suggested Reading
Lopez OL, Jagust WJ, DeKosky ST, et al. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: Part 1. Arch Neurol. 2003;60:1385-1389.
Lopez OL, Jagust WJ, Dulberg C, et al. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: Part 2. Arch Neurol. 2003;60:1394-1399.

PRIMARY PROGRESSIVE APHASIA OFTEN CONFUSED WITH ALZHEIMER’S DISEASE

Nearly a quarter of all dementias, especially those of presenile onset, may be caused by diseases other than Alzheimer’s disease—and some of these atypical dementias involve cognitive abnormalities in areas other than memory, according to a report in the October 16 New England Journal of Medicine.

Primary progressive aphasia is a dissolution of language with memory relatively preserved. Its diagnosis is frequently overlooked in general clinical practice, said M.-Marsel Mesulam, MD, Director of the Cognitive Neurology and Alzheimer’s Disease Center at Northwestern University in Chicago. Patients with primary progressive aphasia come to medical attention because of the onset of word-finding difficulties, abnormal speech patterns, and glaring spelling errors. Some patients cannot find the right words to express their thoughts. Others cannot understand the meaning of words either heard or seen. Still others cannot name objects in their environment. In some patients with primary progressive aphasia, the ability to write language may be less impaired than the ability to speak it. Others develop agrammatism, Dr. Mesulam noted.

Based on his review, language is the only area of prominent dysfunction for at least the first two years of primary progressive aphasia, he added. In these patients, structural brain imaging studies do not reveal a specific lesion that can account for the language deficit, Dr. Mesulam said. Language difficulties may be the patient’s only symptoms for 10 to 14 years. Other cognitive impairments may emerge, but the language deficit remains the primary feature throughout the illness and progresses more rapidly than deficits in other areas. Also—in contrast to many patients with Alzheimer’s disease, who tend to lose interest in recreational and social activities—some individuals with primary progressive aphasia maintain and even intensify their involvement in complex hobbies such as gardening, carpentry, sculpting, and painting, he noted.

In patients with suspected primary progressive aphasia, evaluation by a speech therapist is useful for exploring alternative communication strategies, Dr. Mesulam said. Unlike patients with Alzheimer’s disease, who cannot retain new information in memory, patients with primary progressive aphasia can recall and evaluate recent events even though they may not be able to express their knowledge verbally.

Currently, there is no effective pharmacologic treatment for primary progressive aphasia, Dr. Mesulam said. However, from the vantage point of research, the condition provides a rare opportunity for investigating the molecular mechanisms of focal neurodegeneration and the neuropsychological organization of language function.

NR

Suggested Reading
Mesulam MM. Primary progressive aphasia—a language-based dementia. N Engl J Med. 2003;349:1535-1542.

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