RELIEVING POSTSTROKE DEPRESSION MAY ALSO RESTORE COGNITION

Individuals treated for depression after a stroke receive the added benefit of restored concurrent cognitive impairment, according to a study in the July issue of Stroke. According to the researchers, this is the first time that a double-blind trial demonstrated a partially reversible cognitive dysfunction in stroke patients when their depressive disorder was successfully treated.

In an attempt to establish a firm link between poststroke depression and cognitive impairment, the researchers recruited 33 patients with major depression and 14 patients with minor depression. The subjects were randomly assigned to receive either nortriptyline or placebo treatment. There were no differences in stroke type, lesion location, or neurologic deficits between the two groups. The Hamilton Rating Scale for Depression (HAM-D) and the Mini-Mental State Examination (MMSE) were used to assess response.

According to HAM-D scores, mood improved more quickly in the treated group than in the placebo group. Response—defined as a greater than 50% reduction in HAM-D score and no longer meeting criteria for major or minor depression—was more common in the treated group (76%) than in the placebo group (31%). No differences in MMSE scores were found between the two groups, they noted.

Significant improvements in MMSE score were found, however, when patients were classified by treatment response, the researchers said. "Patients whose poststroke depression remitted (predominantly associated with nortriptyline treatment) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit (predominantly associated with placebo treatment)." Attention-calculation and recall, they noted, were markedly improved. A more detailed neuropsychologic battery would be needed to sort out how many of the disorders met the criteria for vascular dementia, they noted.

It appears that improved cognitive function relates to mood improvement and not to nortriptyline, the researchers wrote. "Approximately one third of the patients responding to treatment were taking placebo and showed the same cognitive improvement as patients taking nortriptyline." This study indicates that poststroke major depression causes a dementia of depression, they concluded.

"For years, it was thought that if a patient showed no improvement in mental ability after a stroke, the impairment was caused by the stroke lesion and that treating depression wouldn't help, but that clearly isn't true," Dr. Robinson said. The cognitive impairment in patients with poststroke depression is caused by both brain damage and depression, he said, and added that most of these patients can be effectively treated with antidepressants.

Kimura M, Robinson RG, Kosier JT. Treatment of cognitive impairment after poststroke depression: A double-blind treatment trial. Stroke. 2000;31:1482-1486.

TAKING END-STAGE DEMENTIA INTO CONSIDERATION

Despite the high prevalence of advanced dementia, little is known about the prognosis of acutely ill patients who receive hospital care for conditions common among the elderly, such as pneumonia or hip fracture. According to a study in the July 5 JAMA, patients with end-stage dementia carry a fourfold increase in mortality compared with cognitively intact patients following hospitalization.

Since both groups apparently received similar care, the researchers recommended that an emphasis should be placed on palliative care, rather than on curative interventions, when advanced dementia is involved.

The cohort included 97 elderly patients with a hip fracture and 119 elderly patients with pneumonia. All of the patients were older than 70 (range, 71 to 102), and most were women. Cognitive status was assessed using the telephone version of the Mini-Mental State Examination (MMSE) in person. Patients who scored between 18 and 24 were defined as being cognitively intact. Patients with a MMSE score less than 18 and a Global Deterioration Scale score of 6 or 7 were defined as having end-stage dementia. While reviewing the daily hospital charts, the researchers noted the use of nine common hospital procedures that are considered to be moderately to severely painful or uncomfortable.

Within six months of hospitalization, 42 (53%) of the patients with pneumonia and end-stage dementia had died, compared with five (13%) of the cognitively intact patients. Similarly, 21 (55%) of the patients with hip fracture and end-stage dementia had died, compared with seven (12%) of the cognitively intact patients.

There were no differences in the number of burdensome procedures received by end-stage dementia and cognitively intact patients, the researchers found. There did not appear to be any consideration of limiting interventions—such as arterial blood gas measurement, phlebotomy, or urinary catheter insertion—in patients with end-stage dementia. Treatment plans for end-stage dementia patients, they continued, did not address high symptom burdens. "We found no evidence of morphine use to treat dyspnea or efforts to premedicate patients prior to painful interventions such as transferring from bed to chair." No palliative care plans were identified, and there were only a few documented discussions with families about the goals of hospital care, they pointed out.

Burdens are probably greater in patients with dementia, the researchers wrote, because they "cannot understand the reasons for tests or treatments, prepare for them emotionally, refuse them if desired, or request analgesia." Increased attention needs to be directed to relieving pain and other distressing symptoms and minimizing burdensome interventions in hospitalized end-stage dementia patients, the researchers concluded.

In New York, the Task Force on Life and the Law has stated that "society must acknowledge both undertreatment and overtreatment as critical problems in the delivery of modern medical care," pointed out Don Riesenberg, MD, in an accompanying commentary. This study, he noted, appeared to have found examples of both.

Only 24% of patients with end-stage dementia had a standing order for pain medication, he noted. The problem of underprescribing medicine for pain relief is compounded for "difficult" patients who may express their pain in the form of disruptive behavior such as aggression or confusion, he wrote. Physicians and nurses, he continued, may surmise that "pain not expressed is pain not experienced" or may fear that opiate treatment will worsen the delirium.

Conversely, this study found no difference with regard to use of painful procedures. "Patients with dementia with a greater than 50% likelihood of dying are unlikely to gain as much benefit from arterial blood gas measurement and daily phlebotomy as do their cognitively intact counterparts, for whom cure may mean many more years of fully functional life," Dr. Riesenberg said. Moreover, patients with dementia may view an intervention as an assault, resulting in increased anxiety and escalated behavioral disturbances.

Future research, he said, should focus on quality of life of the patient as well as quality of the experience of the patient and family throughout the hospitalization process. Discussions about advance planning should be an agenda item in every encounter with patients with dementia, he added. "A few minutes spent can save a world of suffering."

Morrison RS, Siu AL. Survival in end-stage dementia following acute illness. JAMA. 2000;284:47-52.
Riesenberg D. Hospital care of patients with dementia. JAMA. 2000;284:87-89.

DO PATIENTS KNOW THEIR EPILEPSY?

Researchers from Ohio State University, Columbus, have completed the first objective study evaluating what patients with epilepsy know about their disorder. Patients demonstrated only limited knowledge of epilepsy, according to a report in the June Epilepsia.

The 175 patients had established epilepsy and had been referred to an American tertiary care center. They completed a 13-item questionnaire on topics related to safety, compliance, and legal issues of driving and employment. Findings revealed that 30% of the patients believed epilepsy is a mental disorder or contagious, and 41% believed it is appropriate to place an object in a patient's mouth during a seizure to prevent injury. Only 31.6% responded correctly to the question concerning social issues, "People with seizures may do which of the following activities?" (Possible answers: supervised swimming with trained personnel, exercise, drink one or two beers or wine with dinner, none of the above, all of the above.) Twenty-five percent of patients thought pregnant women with epilepsy should discontinue their anticonvulsant drugs.

Two of the lowest scores pertained to the legal issues of driving and employment. Approximately 25% of patients believed it is appropriate to drive a motor vehicle if they either "double up on medication," are not driving alone, or are able to "pull over" at the onset of a seizure. Nearly 85% of respondents believed that people with epilepsy can work in many types of jobs, although 52.5% did not know that it is illegal for potential employers to inquire about a diagnosis of epilepsy.

Neither age, sex, number of years with epilepsy, nor years of education correlated with questionnaire scores. Likewise, the study did not support the assumption that older, educated patients with a long history of epilepsy are more knowledgeable about their disorder.

According to the results of the study, patients were more knowledgeable about questions related to compliance than other issues. However, more than 25% of patients in the study reported incorrect information concerning their anticonvulsant therapy.

The lack of knowledge about epilepsy among patients with the disorder is consistent with previous studies. Most patients with epilepsy know little more, or even less, about their disorder than those without epilepsy. The study findings revealed a need in this population for educational intervention, particularly related to injury prevention and the legalities of driving and employment, suggested the authors.

Long L, Reeves AL, Moore JL, et al. An assessment of epilepsy patients' knowledge of their disorder. Epilepsia. 2000;41:727-731.

COGNITIVE TEST MAY PREDICT PRECLINICAL ALZHEIMER'S DISEASE

Clinical tests may predict Alzheimer's disease years before symptoms appear, according to researchers. Specifically, poor performance in abstract reasoning and in retention of verbal material is the strongest predictor of probable Alzheimer's disease at least 10 years before it is diagnosed. Their report was published in the June issue of Archives of Neurology.

The authors based their findings on a retrospective analysis of cognitive tests given to 1,076 participants in the Framingham Heart Study. Between 1975 and 1979, neuropsychologists administered a battery consisting of standardized tests (taken from the Wechsler Memory Scale, the Wechsler Adult Intelligence Scale, and the Multilingual Aphasia Examination) to measure new learning and immediate recall, visual reproduction from memory, verbal associations, abstract reasoning, and other functions.

All subjects were free of Alzheimer's disease, other forms of dementia, and stroke at baseline. Poorer performance at baseline was associated with the development of Alzheimer's disease during the 22-year follow-up.

Reduced cognitive function (within normal limits of performance) foreshadowed Alzheimer's disease, and lower scores on measures of new learning, abstract reasoning, episodic memory, and semantic memory were a predictor of probable Alzheimer's disease.

The long surveillance period and large sample size allowed the researchers to examine the association of test results and the development of probable Alzheimer's disease for two cohorts: those who remained free of dementia for five years and and those who remained dementia-free for 10 years after baseline. Lowered Logical Memory—Retained, Similarities, Paired Associate Learning, and Learning and Immediate Recall composite scores were significantly associated with a higher risk of Alzheimer's disease in the cohort of patients who had remained free of dementia for five years after baseline. Only Logical Memory—Retained and Similarities were significantly associated with a diagnosis of probable Alzheimer's disease in the cohort that was free of dementia for at least 10 years after baseline.

There were no statistically significant correlations between education level, sex, or occupation and any test score. However, lower Controlled Oral Word Association scores were associated with a higher risk of a later diagnosis of probable Alzheimer's disease in patients 75 to 94 years of age, but not in those ages 65 to 74 years. It is possible that earlier-onset Alzheimer's disease is predicted by a different set of variables than older-onset disease and that preclinical decrements in semantic memory predict late-onset Alzheimer's disease, the researchers reported.

The results suggest that a preclinical phase of Alzheimer's disease can precede the appearance of the disease by many years and that this phase can be detected by appropriate neuropsychological testing. The researchers acknowledge that while "this study is not unique with respect to these findings, it lends important support to these conclusions."

Elias MF, Berger A, Wolf PA, et al. The preclinical phase of Alzheimer's disease; a 22-year prospective study of the Framingham cohort. Arch Neurol. 2000;57:808-813.

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