Doris Svetlik

Cortisol secretion and Alzheimer's disease progression

BACKGROUND Mild hypercortisolemia is a frequent concomitant of Alzheimers disease (AD). In an effort to ascertain the relationship between serum cortisol concentration (CORT) and disease progression, aging, and survival, we followed 9 persons with AD, ages from 56 to 84 years, from an original cohort of 19 enrollees with serial cognitive testing and CORT determinations. METHODS The cognitive instrument was a modification of the Alzheimers Disease Assessment Scale-Cognitive (mADAS-COG). Serum cortisol determinations were performed at noon, and an Afternoon Cortisol Test (ACT) was used to obtain an estimate of average CORT. RESULTS Baseline 12:00 hours CORT but not ACT correlated significantly with the change in mADAS-COG (r = .90, p < .01). ACT levels increased as the mADAS-COG increased over time (p = .037), by 0.156 +/- 0.06 microgram/dL for each one-point increase (indicating greater impairment) in cognitive test score. ACT levels did not increase significantly simply with aging. For the entire cohort of 19 subjects, neither baseline ACT nor 12:00 hours CORT was significantly related to survival. CONCLUSIONS Hypercortisolemia in AD appears related to the clinical progression of the disease, but not to aging or length of survival.

An open-label study of memantine treatment in 3 subtypes of frontotemporal lobar degeneration

There are currently no Food and Drug Administration-approved treatments for frontotemporal lobar degeneration (FTLD). The objectives of this study were to explore the tolerability of memantine treatment in FTLD and to monitor for possible effects on behavior, cognition, and function. Forty-three individuals who met clinical criteria for FTLD [21 with frontotemporal dementia (FTD), 13 with semantic dementia (SD), and 9 with progressive nonfluent aphasia (PA)] received 26 weeks of open-label treatment with memantine at a target dose of 20 mg daily. Concurrent treatment with acetylcholinesterase inhibitors was prohibited. Cognitive and functional outcome measures included the Mini Mental State Examination, Alzheimers Disease Assessment Scale-Cognitive (ADAS-cog), clinical dementia rating-sum of boxes, Neuropsychiatric Inventory (NPI), Frontal Behavior Inventory, Executive Interview (EXIT25), Texas Functional Living Scale (TFLS), Geriatric Depression Scale, and Unified Parkinsons Disease Rating Scale-motor scale. Most subjects were able to tolerate the target dose of memantine. A transient improvement was observed on the total NPI score primarily in the FTD group. Variable declines were observed on the ADAS-cog, EXIT25, Frontal Behavior Inventory, NPI, TFLS, and UPDRS scores. The FTD and SD groups declined on most of the cognitive and behavioral outcome measures, but remained stable on the UPDRS, whereas the progressive nonfluent aphasia group remained relatively stable on the ADAS-cog, NPI, and TFLS, but declined on the UPDRS. Memantine was well-tolerated in these subjects. Future placebo-controlled trials of memantine in FTLD are warranted and may have greater power to detect behavioral and cognitive effects if focused on the FTD and SD clinical syndromes.

WHAT DEPRESSIVE SYMPTOMS ARE REPORTED IN ALZHEIMER'S PATIENTS?

Purpose. To ascertain the nature of depression‐related symptoms in AD.

Can Alzheimer's disease and dementias with Lewy bodies be distinguished clinically?

To determine if Alzheimer’s disease (AD), its Lewy body (LB) variant (LBV), and diffuse LB disease (DLBD) are distinguishable at initial clinical evaluation, data from autopsy-confirmed AD, LBV, and DLBD were examined. No significant differences were found in age at onset, age at death, total duration of illness, duration of illness before initial visit, duration of illness from initial visit to death, or severity of illness at initial evaluation. Hallucinations and delusions were significantly more frequent for LBV and DLBD, respectively, than for AD, and falls were more frequent for DLBD than for AD. Extrapyramidal symptoms (EPS) were less frequent in neuroleptic-free AD subjects than in LB subjects; the percentage of AD patients with EPS after neuroleptic exposure was less than that among LB patients. Seizures were significantly more common for DLBD than for AD or LBV. LB dementias differed from AD at initial evaluation, with more frequent hallucinations and delusions, EPSs, and seizures, and longitudinally in neuroleptic sensitivity, but the data did not distinguish LBV from DLBD.

Caregiver resentment: Explaining why care recipients exhibit problem behavior

Caregivers of CI elders reported providing more care inresponse to CI-related care recipient disturbing behavior. However, beyond the source of impairment,disturbing (externally attributable) behavior typical of CI, and amount of care provided, resentment waspredicted by controlling and manipulative (internally attributable) care recipient behavior.

Responsiveness of the Quality of Life in Late-Stage Dementia Scale to Psychotropic Drug Treatment in Late-Stage Dementia

Background: We report on the responsiveness of a previously validated quality-of-life scale, the Quality of Life in Late-Stage Dementia scale (QUALID), as an outcome measure in a clinical trial of two psychotropic medications. Methods: Secondary analyses were conducted comparing outcome measures used in a randomized double-blind trial of two antipsychotics (olanzapine and risperidone) for the treatment of dementia-related behavioral symptoms. The QUALID was completed for 31 of the patients in addition to several measures of behavior-related dementia symptoms including the Neuropsychiatric Inventory, the Withdrawn Behavior subscale of the Multidimensional Observation Scale for Elderly Subjects, the Mini-Mental State Examination, and the Clinical Global Impression. Measures of safety and adverse effects included the Simpson-Angus Scale and records of specific adverse events. Results: A significant positive relationship was found between QUALID score and improvement in behavioral symptoms, and a negative association was found with adverse medication effects. Conclusions: The QUALID was sensitive to both the treatment effects and the adverse effects of medication in this sample of patients.

Cortisol secretion and Alzheimer's disease progression : a preliminary report

We report preliminary findings in a study of the relationship of plasma cortisol concentration (CORT) to the clinical progression of Alzheimers disease (AD), testing the hypotheses that CORT predicts AD progression and that CORT increases as the disease advances. In 12 subjects with NINCDS/ADRDA probable AD, we performed cognitive testing and plasma cortisol determinations at baseline and again in 12 months. A modified Alzheimers Disease Assessment Scale-Cognitive (ADAS-COG) measured disease progression. Plasma cortisol concentration CORT was determined at 12 AM and 1 PM, and an Afternoon Cortisol Test (ACT) was used to estimate average 24-hr CORT. Baseline 12 AM CORT correlated with the change in ADAS-COG from start of study to 12 months. No cortisol measure increased over the study period; estimated average 24-hr CORT and 12 AM CORT remained constant, whereas while 1 PM CORT declined. There was no relationship between age or duration of illness and any of the cortisol measures at baseline.

Comparison of Alzheimer's Disease in Native Americans and Whites

OBJECTIVE This study compared medical history and findings on initial clinical examination in Native Americans diagnosed with possible or probable Alzheimers disease (AD) at Native American satellite clinics of the University of Texas (UT) Southwestern Medical Centers Alzheimers Disease Center with those of Whites diagnosed with probable AD at the UT Southwestern Medical Centers Alzheimers Disease Clinic. METHODS The information reviewed was contained in the database of the UT Southwestern Alzheimers Disease Center. RESULTS In relation to Whites, Native Americans had slightly but significantly greater age at onset of symptoms (71.7 vs. 69.6 years, t = -2.08, p = .04) and equivalent cognitive scores at evaluation (Mini-Mental State Exam score = 17.4 vs. 18.5, t = 0.98, p = .33), despite significantly lower educational level (11.4 vs. 13.4 years, t = 5.63, p < .001). Native Americans were more frequently depressed on examination (22.8% vs. 9.5%, chi2 = 12, p = .001) and reported diabetes, hypertension, and heart disease significantly more often than did Whites (p < .01 for all), but their survival time after AD diagnosis was similar to that of Whites despite these comorbidities. CONCLUSIONS With the exception of a greater prevalence of depression and cardiovascular risk factors in Native Americans than in Whites, Native Americans had a course of illness similar to that of Whites.

Caregiver burden in Alzheimer's disease: Case studies

A series of individual caregivers were studied in a program for reducing caregiver burden. Using a modified caregiver burden inventory for assessment, an educational program and a needs-based intervention algorithm to guide intervention of caregivers, attempts were made to mitigate caregiver burden. A study of individual cases suggested that primary burden for caregivers included time spent in caring for loved ones and missing out on phase-of-life-appropriate activities. It was our impression that caregiver burden did not represent an appropriate outcome measure in this situation, and that the most desired outcome was the openness of individuals to assistance when and where they were able to accept it.

Comparison of functional and cognitive donepezil effects in Alzheimer's disease

Donepezil has been shown to improve aspects of cognitive functioning in persons with Alzheimers disease (AD), but its impact on instrumental activities of daily living has received little attention. In a within-subject design, 24 community-dwelling persons with AD were treated with open-label donepezil over a 12-month period. To assess functional abilities, a brief, objective measure of instrumental activities of daily living skills was used (Texas Functional Living Scale; TFLS). Global cognitive abilities were assessed with the Mini-Mental State Examination (MMSE). Changes in TFLS and MMSE scores were much the same. Improvements on the TFLS and MMSE were seen over a 3-month period. At 12 months, both TFLS and MMSE scores declined slightly below baseline. These results support an effect of donepezil on cognitive measures and day-to-day function and also suggest that the MMSE reflects well the actual functional ability of persons with moderate AD.