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 Alzheimer's 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 Alzheimer's 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.

Cortisol secretion and Alzheimer's disease progression.

BACKGROUND: Mild hypercortisolemia is a frequent concomitant of Alzheimer's 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 Alzheimer's 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.

Altered amyloid protein processing in platelets of patients with Alzheimer disease.

BACKGROUND: beta-Amyloid peptide, the core component of neuritic plaques in brain areas in patients with Alzheimer disease (AD), is 1 cleavage product of the beta-amyloid precursor protein (APP) in neurons and platelets. Alternate cleavage products of intact 140- to 150-kd APPs in platelets include nonamyloidogenic 120- to 130-kd and 110-kd isoforms. The possible differential significance of these 2 isoforms, structurally similar to protease nexin II, is unknown. OBJECTIVE: To determine whether the ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform as processed in platelets correlates with the presence of AD and/or the apolipoprotein E4 (ApoE4) allele, which is a major risk factor for AD. SETTING: The Alzheimer Disease Center at The University of Texas Southwestern Medical Center at Dallas. METHODS: The APP isoforms were quantitated with the use of 2 different Western blot detection methods in platelets from 15 patients with AD and 19 control subjects in whom genotyping of apolipoprotein E was performed. RESULTS: The mean ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform in the patients with AD was significantly lower than that of the control subjects (5.98 vs 7.64; P = .03 [method 1] and 5.98 vs 7.92; P = .01 [method 2]) after adjusting for age and the increased incidence of ApoE4 in patients with AD. The lower APP ratios were also associated with increased age and with the presence of an ApoE4 allele. CONCLUSIONS: The APP processing in platelets of patients with AD is different from that of control subjects. This difference, largely caused by factors other than the ApoE4 genotype, may reflect chronic platelet activation in patients with AD. The use of these data to estimate "AD risk," by using the APP isoform ratio, indicates an odds ratio of 1.75, suggesting possible utility as an adjunct in the diagnosis of AD. Moreover, these findings may relate to analogous alterations in APP processing that may occur in brain areas affected by AD.

Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Experiences with depression in a dementia clinic.

Of 317 consecutive cases seen in a dementia clinic, 19 (6%) had little or no objective evidence of cognitive impairment on clinical examination and extensive neuropsychological testing. Of the remaining 298 cases, 192 (64%) were diagnosed as probable or possible Alzheimer's disease (AD). Of the 19 nondemented cases, 8 (42%) were thought to have cognitive difficulty due to depression. In the AD group, only 4 cases (2%) were thought to be depressed and only 2 of the 4 met DSM-III-R criteria for major depression. There was no relationship between Hamilton Rating Scale for Depression scores and either cognitive or behavioral measurements of dementia severity, suggesting that the difference between the two groups was not due to underreporting by AD patients. The authors concluded that a tertiary care setting, depression is a common cause of cognitive complaints in persons without organic disease and a rare cause of excess morbidity in AD.

Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease patients.

BACKGROUND: This open-label study examined the effects of the reversible cholinesterase inhibitor donepezil on emotional/behavioral symptoms in Alzheimer's disease (AD) patients. METHOD: Patients were diagnosed as having probable/possible AD by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria. This study used the CERAD Behavior Rating Scale for Dementia (CBRSD) and its subscales to evaluate a group of 25 AD patients treated with donepezil. Dosage was increased at 4 months for most patients from 5 to 10 mg q.h.s. Analysis of variance was used to compare scores over a period of 12 months. These patients were also compared, using t tests, to a reference group that had received no donepezil or other anticholinesterase. RESULTS: Donepezil administration was associated with improvement in Mini-Mental State Examination (MMSE) and CBRSD total scores at 3-month evaluation (p< or =.05). CBRSD depression and behavioral dysregulation scores improved transiently at 4 months (p< or =.05). MMSE, CBRSD total, CBRSD depression, and CBRSD behavioral dysregulation scores returned to baseline levels at 12 months, in contrast to the reference group, whose MMSE and CBRSD total scores worsened minimally over the 12 months. CONCLUSION: Donepezil has a mildly positive effect on emotional/behavioral symptoms in AD in addition to its effect on cognitive function.

The quality of life in late-stage dementia (QUALID) scale.

OBJECTIVES: To develop a valid and reliable instrument for rating quality of life in persons with late-stage Alzheimer's disease and other dementing illnesses. DESIGN: A group of clinicians with extensive experience in dealing with dementia patients developed by consensus the Quality of Life in Dementia Scale (QUALID), an 11-item scale. The window of observation for each subject was 7 days. A 5-point scale captured the frequency of each item (total score ranging from 11 to 55). Lower scores reflected a higher quality of life (QOL). Validity was assessed by comparison with other measures. SETTING: Dementia special care unit. PARTICIPANTS: Professional caregivers of 42 patients. MEASUREMENTS: QUALID, Mini-Mental State Exam (MMSE), Physical Self-Maintenance Scale (PSMS), Neuropsychiatric Inventory (NPI), and Geriatric Depression Scale (GDS). RESULTS: QUALID scores ranged from 12 to 45 points and were skewed toward higher QOL (lower scores). Internal consistency of items was high, as were test-retest reliability and consistency across recorders. As expected, there was no relationship between QUALID and MMSE or PSMS scores, but there was a statistically significant, although moderate, relationship between QUALID and NPI, and GDS scores. CONCLUSION: The QUALID is a reliable and valid scale, administered to caregivers, for rating QOL in persons with late-stage dementing illness.

Specialty nursing council: a peer support group for nurses in independent roles.

As nurses move into more nontraditional, expanded roles, they sometimes lack a social and professional support group within the work setting. Feeling isolated and lacking support, several clinical nurse specialists (CNSs) at a large county institution began the Specialty Nursing Council. The Specialty Nursing Council provides a means of networking and support for nurses in specialty roles in a three institution health care campus. Monthly meetings are conducted to bring members together and for continuing education programs. The keys to success in forming this type of council are: 1) a dedicated group that plans, organizes, and distributes informational material; 2) common goals and objectives; 3) direct benefits to members.

What depressive symptoms are reported in Alzheimer's patients?

PURPOSE: To ascertain the nature of depression-related symptoms in AD. METHOD: The Hamilton Rating Scale for Depression (HAM-D) was administered as a semi-structured interview to 30 consecutive Alzheimer's disease (AD) patients who also underwent independent psychiatric evaluation. The HAM-D was also administered with a caregiver as the informant. RESULTS: There was no relationship between the number of symptoms reported by patients or caregivers and patients' level of cognitive impairment. Symptom reports by caregivers living in the same household did not differ significantly from symptom reports by caregivers living elsewhere. Caregivers rated AD patients as having significantly more depressive symptoms than did patients themselves. The items most frequently endorsed by caregivers were psychic anxiety (77%), suspiciousness (50%), low energy (50%) and depression (43%). The items most frequently endorsed by AD patients were weight loss (36%), psychic anxiety (33%) and somatic anxiety (33%). Depression was endorsed by 20% of patients. Caregiver-respondent HAM-D scores suggested clinically significant depression in 27% of cases, but AD patients' scores suggested clinically significant depression in only 7% of cases. No case of major depression was found on psychiatric examination. CONCLUSIONS: Depressive symptoms seemed more an executive function loss than of primary mood disturbance in that guilt, suicidal rumination and self-perceived loss of interest were uncommon, suggesting that simple environmental measures might be the most appropriate treatment of these symptoms.

Xenon-133 SPECT-determined regional cerebral blood flow in Alzheimer's disease: what is typical?

A study of 76 consecutive xenon-133 SPECT studies of regional cerebral blood flow was undertaken to determine the frequency of various patterns of blood flow in cases of clinically diagnosed probable and possible Alzheimer's disease. The reference tomographic section was a slice 6 cm above and parallel to the canthomeatal line. With the use of this technique, the "classic" finding of bilateral temporoparietal (TP) flow reductions as the sole abnormality occurred in only 28% of cases. Bilateral TP reductions accompanied by bilateral or unilateral frontal flow reductions were nearly as common (24%), and other patterns accounted for the other 48% of cases.