Jane F. Potter

Aggressive Chemotherapy for Diffuse Histiocytic Lymphoma in the Elderly: Increased Complications with Advancing Age

Twenty patients ≥70 years of age were included in a study of the treatment of diffuse histiocytic lymphoma utilizing cyclophosphamide, adriamycin, vincristine, and prednisone. These patients ranged in age from 70 to 94 years (median 75 years). There were also 55 younger patients (age range 33 to 69 years) in the treatment trial. There were no dose adjustments for age. The complete remission rate in the elderly patients (45 per cent) was not different from that in the younger patients (53 per cent). The overall survival in the elderly patients (median 13 months) was somewhat shorter than that in the younger patients (medians 22 months for patients 56–69 years of age and 41 months for patients 33–55 years of age), but not significantly different. Death during the first two treatment cycles from causes other than lymphoma occurred in 25 per cent of the patients ≥70 years of age versus 2 per cent of younger patients (P < 0.01). In addition, three other patients aged 79, 65, and 59 years died in the fourth or fifth cycles of treatment from causes other than lymphoma. Thus, 30 per cent of patients ≥70 years of age died during therapy from causes other than lymphoma, versus 5 per cent of younger patients (P < 0.01). Whether this altered ability to tolerate therapy in the older patients reflected decreased marrow function, altered drug metabolism, other effects of aging, or a combination of these factors is not clear. It might be appropriate to alter drug doses when treating elderly patients, and particular attention to supportive measures seems appropriate.

Low body mass index in demented outpatients

In order to determine the association between dementia and low body weight in outpatients, Body Mass Index (BM1) was evaluated prospectively in 346 frail elderly outpatients presenting for comprehensive geriatric assessment. Patients were categorized into four groups (cognitively intact, dementia of the Alzheimers type (DAT), other dementia, and patients with depressive symptoms). Patients were assessed for severity of dementia by the Clinical Dementia Rating scale. Differences between groups for various clinical parameters were evaluated using an analysis of variance and Duncans Multiple Range Test. Patients with dementia, regardless of etiologic type or severity, and patients with depressive symptoms had BMIs ≥10% lower than the cognitively intact patients. BMI was positively correlated with Instrumental Activities of Daily Living (IADL) but not Activities of Daily Living (ADL) or Mini‐Mental State Exam (MMSE) score. Low BMI was not associated with increased physical illness. In fact, in the subset of patients with DAT, lower BMI correlated with significantly lesser amounts of comorbid physical illness. Finally, compared to cognitively intact outpatients, patients with DAT appeared to be physically healthier despite their having a lower BMI.

Hearing impairment as a predictor of cognitive decline in dementia.

Thirty‐eight patients with dementia of various etiologies were studied longitudinally to determine the change in cognition over time in subjects with and without hearing impairment. Hearing impaired subjects were older (P < .0001), but subject groups were otherwise comparable with respect to living arrangements, medical illness, number of drugs taken, mood, years of education, and cognitive functioning at the beginning of the study period. Decline in cognitive functioning at follow‐up was greater in hearing impaired subjects and this difference persisted after adjustment for the greater age of hearing impaired subjects (P< .009). Further division of subjects by diagnosis showed that only in the Alzheimers group did hearing impairment predict more rapid cognitive decline at follow‐up.

Caregiver burden should be evaluated during geriatric assessment

This study examines the relationship between caregiver burden and use of long‐term care services following geriatric assessment. One hundred nine older subjects underwent comprehensive assessment, which included a questionnaire completed by the primary caregiver to assess the sense of burden in providing care. Logistic regression was used to identify independent predictors of service use at 12 months. Among measures of the older persons cognitive and physical abilities, only activities of daily living predicted increased use of services. When the measure of caregiver burden was added, it also entered as an independent predictor, which significantly improved the prediction of service use (χ2 = 5.9, P < .02). In a separate analysis, caregiver burden predicted both the use of home services and nursing‐home placement. During longitudinal follow‐up, the measure of burden decreased over 12 months for the sample, with the greatest reduction in burden occurring for caregivers whose relative was placed in a nursing home. The fact that caregiver burden was the most important factor in determining who would use formal services suggests that burden should be evaluated as part of geriatric assessment.

Insights into the neurodegenerative process of Alzheimer's disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity.

Since the first description of Alzheimers disease (AD) in 1907, significant progress was made into understanding disease pathophysiology. The enormous effort in AD research has translated into the discovery of genetic linkages for disease, into elucidating the structure and function of the etiologic β‐amyloid protein, and into unraveling the seemingly complex neuroimmunological cascade that affects neuronal dysfunction. Although effective therapies do not currently exist, many are being developed. We propose that the neuropathogenesis of AD, in measure, revolves around the immunological activation of glial cells, which in turn leads to alterations in inflammatory neurotoxin production, and ultimately to neuronal injury and death. Elucidating the mechanisms involved in such glial cell immune activation should provide valuable insights into understanding the disease process and in providing effective therapeutics to prevent and/or retard the devastating neurodegeneration that afflicts so many of our elderly. J. Leukoc. Biol. 65: 416–427; 1999.

The Reliability and Validity of the Geriatric Depression Rating Scale Administered by Telephone

OBJECTIVE: To evaluate prospectively the reliability and validity of the Geriatric Depression Scale administered by telephone (T‐GDS) in patients undergoing outpatient comprehensive geriatric assessment.

Methylphenidate for Apathy and Functional Status in Dementia of the Alzheimer Type

OBJECTIVE Apathy is the most common behavioral problem in persons with dementia of the Alzheimer type (DAT). Treatment of apathy in DAT is not systematically studied. The purpose of this study was to evaluate the response of apathy to methylphenidate treatment and to examine whether functional status improved. METHODS The authors conducted a 12-week open-labeled study with immediate release formulation of methylphenidate. Twenty-three patients with DAT scoring >40 on the Apathy Evaluation Scale (AES) were recruited. Repeated measures analysis of variance and correlation analysis were performed. RESULTS None of the patients dropped out of the study because of adverse events. Significant improvement in apathy was noted during 12 weeks. Significant improvement was also noted in depression, Mini-Mental State Examination score, and functional status. There was no correlation between changes in the AES and depression scores. CONCLUSIONS Methylphenidate was well tolerated in these patients with DAT. Apathy improved with the use of methylphenidate.

Disagreement in the Reporting of Depressive Symptoms Between Patients With Dementia of the Alzheimer Type and their Collateral Sources

The authors investigated sources of disagreement on the Geriatric Depression Scale (GDS) between patients and their collateral sources (CSs). There were 198 subjects with possible or probable Alzheimers disease (DAT) and 64 cognitively intact subjects evaluated at an outpatient geriatric assessment center. The 30-item GDS was completed by the patient and the CS version of the GDS by the CS. A sizable discrepancy was found in the reporting of depressive symptoms by the subjects vs. the CSs. Multiple-regression analyses revealed that both level of insight and level of physical illness in the subjects with DAT significantly influenced the discrepancy. An increased sense of burden in the CSs was associated with a larger symptom gap in both DAT and control subjects. CSs consistently perceived more depressive symptoms than subjects, especially subjects with DAT who had no insight into their cognitive impairment.

The effect of HMG-CoA reductase inhibitors on cognition in patients with Alzheimer's dementia: a prospective withdrawal and rechallenge pilot study.

BACKGROUND Statins are well-known for their cardiovascular benefits. However, the cognitive effects of statins are not well understood. We hypothesized that individuals with preexisting dementia would be more vulnerable to statin-related cognitive effects. OBJECTIVE The aim of this study was to evaluate the impact on cognition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) discontinuation and rechallenge in individuals with Alzheimers dementia (AD) on statins at baseline. METHODS A 12-week prospective, open-label study was conducted in a geriatric clinic setting. Eighteen older subjects underwent a 6-week withdrawal phase of statins followed by a 6-week rechallenge. The primary outcome measure was cognition, measured by the Mini-Mental State Examination (MMSE); secondary outcome measures were the Consortium to Establish a Registry for Alzheimers Disease (CERAD) neuropsychological battery, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and fasting cholesterol. The change in outcome measures was assessed using repeated-measures ANOVA and paired t tests. RESULTS At the end of the intervention, there was a significant difference across time for MMSE score (P = 0.018), and total cholesterol (P = 0.0002) and a trend toward change across time for ADL (P = 0.07) and IADL (P = 0.06) scale scores. Further analyses using paired t tests indicated improvement in MMSE scores (Δ1.9 [3.0], P = 0.014) with discontinuation of statins and a decrease in MMSE scores (Δ1.9 [2.7], P = 0.007) after rechallenge. Total cholesterol increased with statin discontinuation (P = 0.0003) and decreased with rechallenge (P = 0.0007). The CERAD score did not show a change across time (P = 0.31). There was a trend toward improvement in ADL (P = 0.07) and IADL (P = 0.06) scale scores with discontinuation of statins, but no change with rechallenge. CONCLUSIONS This pilot study found an improvement in cognition with discontinuation of statins and worsening with rechallenge. Statins may adversely affect cognition in patients with dementia.

Simvastatin-Induced Decline in Cognition

Objective: To describe a case of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy. Case Summary: A 64-year-old man developed cognitive difficulties within one week after starting simvastatin 40 mg/day. There was a 3 point decline from baseline in the Mini-Mental State Exam (MMSE) score 2 weeks after simvastatin was initiated, as well as declines in the Activities of Daily Living and Instrumental Activities of Daily Living scales. Simvastatin was discontinued, and the patients cognition improved to baseline within 6 weeks. Rechallenge with simvastatin at half the original dose was attempted. His cognition deteriorated over a 2 week period. Simvastatin was stopped, and the patients MMSE scores returned to baseline within 4 weeks. Discussion: This patient developed new-onset problems with short-term memory, long-term memory, and item misplacement in addition to the baseline problems with names and word-finding that had been present prior to beginning statin therapy. Decreased cognition identified with neuropsychological tests has been shown in clinical trials with simvastatin; however, as of August 23, 2006, this is the first report of cognitive and functional problems that have been documented using standardized instruments. The Naranjo probability scale revealed a highly probable adverse reaction of cognitive decline associated with simvastatin therapy. Conclusions: Statins are commonly used in the older population. Simvastatin appeared to be associated with worsened cognition in our patient, an older person with preexisting memory problems. Statins should be used with caution in this vulnerable population.