Iron-Insensitive Quantitative Assessment of Subcortical Gray Matter Demyelination in Multiple Sclerosis Using the Macromolecular Proton Fraction.

BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping. MATERIALS AND METHODS: Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data. RESULTS: The macromolecular proton fraction in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to patients with relapsing-remitting MS and from those with relapsing-remitting MS to patients with secondary-progressive MS. The macromolecular proton fraction in all subcortical structures significantly correlated with the Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range of 0.4-0.6. Significant correlations (r = -0.4 to -0.6) were also identified between the macromolecular proton fraction and the 9-Hole Peg Test, indicating a potential relationship with nigrostriatal pathway damage. Among T2* values, weak significant correlations with clinical variables were found only in the putamen. The macromolecular proton fraction did not correlate with T2* in any of the studied anatomic structures. CONCLUSIONS: The macromolecular proton fraction provides an iron-insensitive measure of demyelination. Myelin loss in subcortical GM structures in MS is unrelated to excess iron deposition. Subcortical GM demyelination is more closely associated with the disease phenotype and disability than iron overload.

Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: The Kame Project.

BACKGROUND: The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin. OBJECTIVE: To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women. METHODS: A prospective observational study in a population-based cohort of older Japanese Americans (aged > or =65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use. RESULTS: Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, -0.41; SEM, 0.50; P =.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35). CONCLUSIONS: Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.

Phase I study of a humanized anti-CD11/CD18 monoclonal antibody in multiple sclerosis.

OBJECTIVE: To evaluate the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of a humanized anti-CD11/CD18 monoclonal antibody (Hu23F2G) in patients with multiple sclerosis. METHODS: In this phase I uncontrolled dose escalation study, patients (n = 24) with primary or secondary progressive multiple sclerosis received single intravenous infusions of Hu23F2G (0.01 to 4.0 mg/kg). Study parameters included safety, pharmacology, immunogenicity, and brain magnetic resonance imaging (MRI). RESULTS: Hu23F2G had few adverse effects, but 2 cases of urinary tract infection and 2 cases of gingivitis did occur. Transient leukocytes developed in some subjects receiving > or = 1.0 mg/kg. The pharmacokinetic response was nonlinear, with the area under the curve increasing out of proportion to the increase in dose. The mean terminal half-life increased with dose and was 21.9 (SD, 12.8) hours at the 4.0 mg/kg dose. High saturation (> 80%) of CD11/CD18 on circulating leukocytes was achieved with doses > or = 0.2 mg/kg. The duration of high leukocyte saturation was dose-dependent, persisting for more than a week at the 4.0 mg/kg dose. A marked decrease in leukocyte migration in response to cutaneous inflammation was observed. Antibodies against Hu23F2G were not detected. The neurologic examinations were stable except for 1 subject who had worsening weakness associated with an infection. No significant changes were noted on brain MRI scans. CONCLUSIONS: Hu23F2G was tolerated at doses that achieved high degrees of leukocyte CD11/CD118 saturation with in vivo inhibition of leukocyte migration. Because this phase I study was not designed to determine the clinical efficacy of Hu23F2G, further studies are needed.

Myasthenia gravis associated with T helper cell lymphoma.

A case of myasthenia gravis (MG) associated with a T helper cell lymphoma is reported. Treatment of the lymphoma led to resolution of the MG. This and other cases of hematologic tumors associated with MG suggest that immunoregulatory abnormalities may underlie the production of antibodies directed against the acetylcholine receptor.

Relationship between cigarette smoking and Alzheimer's disease in a population-based case-control study.

We investigated whether cigarette smoking is negatively associated with Alzheimer's disease (AD) in a population-based, frequency-matched, case-control study of 152 AD patients and 180 controls. Ever having smoked was associated with lower risk of AD (adjusted odds ratio = 0.61; 95% confidence interval: 0.37-0.99). Additional multivariate analyses demonstrated that education and history of hypertension modified this association. The direction of the modification was for higher education level and history of hypertension to further reduce the risk. The "dose-response" pattern showed the greatest risk reduction among those who smoked least and suggests a biologic mechanism of a dose-dependent up-regulation of nicotinic (cholinergic) brain receptors. These data, although consistent with current opinion about pathophysiology of AD, do not suggest smoking should be used as a preventive strategy for AD.

Predictors of mortality in patients diagnosed with probable Alzheimer's disease.

OBJECTIVE: We sought to identify factors associated with mortality in persons recently diagnosed with probable Alzheimer's disease (AD). BACKGROUND: Predicting mortality in AD in needed both in patient care and public health planning. Previous studies have identified several factors which contribute to mortality in AD, but few longitudinal studies of population-based cohorts exist. METHODS: In a longitudinal follow-up study 327 patients with newly diagnosed probable AD (mean Mini-Mental State Examination [MMSE] score of 20) from a large, stable health maintenance organization were identified. Demographic characteristics, dementia severity, and comorbid conditions were identified at enrollment. Patients were followed longitudinally (median 3.3 years, total 898 person-years). Baseline characteristics were used to predict survival in univariate and multivariate models. RESULTS: Increased mortality was seen in patients with probable AD (9.0 deaths per 100 person-years) compared with the community population adjusted for age and gender (4.3 deaths per 100 person-years). On univariate analysis we found increased age, male gender, impairment on MMSE or Blessed dementia rating scale (DRS), rate of MMSE decline, wandering or agitation, vascular disease, and sensory impairment affecting the ability to read or hear to be moderately associated with decreased survival. After adjusting for age and gender in a multivariate model, Blessed DRS score and sensory impairment affecting the ability to read were independently associated with decreased survival. CONCLUSIONS: Short-term mortality is increased in patients newly diagnosed with probable AD. Measures of dementia severity, measures of general debility, and vascular disease are associated with increased mortality. Of these, general debility and sensory impairment were more strongly associated with shortened survival.

Accelerated decline in apolipoprotein E-epsilon4 homozygotes with Alzheimer's disease.

BACKGROUND: The apolipoprotein E-epsilon4 (APOE-epsilon4) allele is a powerful genetic risk factor for the development of Alzheimer's disease (AD). AD patients who are APOE-epsilon4 homozygotes have an earlier age at onset, increased amyloid burden, and decreased acetylcholine levels--findings that suggest differences in disease severity or rate of progression. Studies of genotype differences in rate of decline, however, have produced negative results that may be due to methodologic biases. The current study examined rate of decline in the largest sample of APOE-genotyped AD patients for whom longitudinal cognitive data have been reported. METHODS: Newly diagnosed patients with probable AD (n = 201) comprised four genotype groups: epsilon2/3 (n = 14), epsilon3/3 (n = 75), epsilon3/4 (n = 82), and epsilon4/4 (n = 30). The Dementia Rating Scale (DRS) was administered at baseline and then annually for 1 to 6 years (mean, 2.5 years). For each subject, a DRS slope was calculated reflecting annual rate of decline. Rate of decline as measured by DRS slope differed according to genotype, with the effect modified by DRS score (p < 0.014). At the mean DRS score observed in our sample (DRS = 105), the epsilon4/4 group had an increased rate of decline (11.9 points per year) relative to the epsilon2/3 (5.8 points per year; p < 0.003), epsilon3/3 (9.3 points per year; p < 0.076), and epsilon3/4 (9.6 points per year; p < 0.055) groups. At a lower DRS score (DRS = 80), even larger differences were observed among genotypes; the epsilon4/4 group had a increased rate of decline (22.2 points per year) relative to the epsilon2/3 (9.7 points per year; p < 0.0006), epsilon3/4 (15.8 points per year; p < 0.020), and epsilon3/3 (18.2 points per year; p < 0.173) groups. The epsilon2/3 group had a significantly slower rate of decline than all other groups at DRS scores of 80 or 105. CONCLUSIONS: APOE-epsilon4 homozygosity is associated with a faster rate of cognitive decline, whereas the epsilon2 allele slows disease progression. These findings suggest that APOE plays a mechanistic role in the progression of AD, and is not simply related to disease onset.

Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status.

OBJECTIVE: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period. METHODS: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese-American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of > or =5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE). RESULTS: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-epsilon4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the epsilon4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62. CONCLUSIONS: Unexplained olfactory dysfunction in the presence of one or more APOE-epsilon4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Head circumference and incident Alzheimer's disease: modification by apolipoprotein E.

BACKGROUND: The clinical expression of AD likely occurs when the accumulation of degeneration in specific brain regions leads to the descent below a critical threshold of "brain reserve" beyond which normal cognitive function cannot be maintained. The association between head circumference (HC), a measure of brain reserve, and the incidence of probable AD was examined in a large nondemented cohort that has been followed since 1992 and its modification by APOE epsilon 4 genotype. METHODS: Fifty-nine incident cases of probable AD were identified from 1,869 initially nondemented individuals seen at the baseline examination (1992 to 1994) and followed for a mean of 3.8 years. Variables measured at baseline included age, education, gender, HC, height, weight, and score on the National Adult Reading Test-Revised. APOE was genotyped at the time of the first biennial examination (1994 to 1996) and was available for 1,111 individuals in the cohort. Cox proportional hazard regression was performed to estimate hazard ratios (HR) for probable AD for HC and other covariates. RESULTS: Incident cases were significantly older, less educated, shorter, and lighter, had lower estimated verbal IQ scores, and were more likely to have at least one APOE epsilon 4 allele than unaffected individuals. The HR associated with the lowest tertile of HC (<21.4 inches) adjusted for education, gender, and APOE epsilon 4 was 2.3 (95% CI 0.7 to 6.9, p = 0.16). The HR for one or two APOE epsilon 4 alleles was significant (HR = 4.8, 95% CI 1.8 to 12.9, p = 0.002). The combination of low HC and APOE epsilon 4 strongly predicted earlier onset of AD with HR = 14.1 (95% CI 3.0 to 65, p = 0.0007). CONCLUSIONS: Smaller HC, in the presence of the APOE epsilon 4 allele, hastens the age at onset of AD. These results support the brain reserve hypothesis and its importance in precipitating the clinical expression of AD among genetically predisposed individuals.

Apolipoprotein E in Alzheimer's disease risk and case detection: a case-control study.

The objective of this study was to describe the association between the epsilon 4 allele of the apolipoprotein E gene (APOE E4) and Alzheimer's disease (AD) and to evaluate APOE E4 genotyping as a test for AD. The study base of this case-control study included about 23,000 persons 60 year of age or greater (a large health maintenance organization); the demographic characteristics of this group are similar to those of the surrounding area. Analysis focused on 234 Caucasian probable AD patients first identified between 1987 and 1993; and 304 cognitively intact controls of similar age, sex, and race who were randomly selected from the same study base. All cases were examined and diagnosed by study physicians using standard protocols. All subjects participate in continuing annual follow-up testing to verify their cognitive status. APOE genotypes were determined from blood samples using standard laboratory methods. Subject characteristics and diagnoses were obtained from interviews, diagnostic examination, or medical record review. Heterozygous E4 individuals had a crude odds ratio of 3.1 (2.1-4.5) for AD compared to those with no E4, while homozygous E4 subjects had an odds ratio of 34.3 (8.0-146.3) for AD. As an indicator of AD, having one E4 allele showed a sensitivity of 0.52 and a specificity of 0.74. Homozygous E4 genotype had a sensitivity of 0.23 and a specificity of 0.99 (when compared to non-E4 genotypes). Cardiovascular disease differed in cases and controls, but did not confound or modify the APOE E4-AI) association. In this study base, the APOE E4 allele was a significant risk factor. However, considering either homozygous or heterozygous E4 genotype as a screen or diagnostic marker for AD would miss many true cases and could misclassify many normals as AD.

Healthcare utilization and costs in managed care patients with Alzheimer's disease during the last few years of life.

OBJECTIVES: To learn whether managed care patients with Alzheimer's disease (AD) are more or less costly to care for than patients with other forms of dementia or patients without dementia during the last few years of life. DESIGN: Case control study. SETTING: A health maintenance organization base population. PARTICIPANTS: Three groups of subjects (mean age 85) who were deceased members of a dementia registry obtained from a health maintenance organization base population: 263 subjects with clinically diagnosed probable AD, 133 subjects with other forms of dementia, and 100 cognitively intact controls. MEASUREMENTS: Utilization records were examined for the 3 years preceding death. RESULTS: In all subcategories and in aggregate, utilization and costs of care were either similar or lower for patients with AD than for the other groups, even after controlling for age, gender, and comorbidity. CONCLUSIONS: Persons with AD do not incur higher costs than persons with other types of dementia or age-matched persons without dementia in a mature health maintenance organization during the last few years of life, when utilization is likely to be highest.

Symptom patterns and comorbidity in the early stages of Alzheimer's disease.

OBJECTIVE: To learn whether patients with early Alzheimer's disease tend to under-report or over-report symptoms and to compare their comorbidity with non-demented patients. DESIGN: Case Control Study in a population-based dementia registry. SETTING AND PATIENTS: Three groups of subjects (mean age 76) were enrolled from an HMO base population: 154 cases had clinically diagnosed probable Alzheimer's disease, 92 subjects were found to be not demented although they had complaints of cognitive impairment, and another 129 cognitively intact controls were enrolled after frequency-matching for age and sex. MEASUREMENTS AND RESULTS: Medical records were examined for the 2 years prior to enrollment. Symptoms suggestive of cognitive impairment were evident 7.8 months prior to enrollment (median 6 months) in 95% of cases, in 77% of the not demented subjects, and in 6% of controls. After corrections for multiple comparisons, only symptoms of cognitive impairment were more frequent in cases, whereas several common symptoms not suggestive of cognitive impairment (eg, gastrointestinal discomfort, joint pain, vision problems) occurred more often in controls and the not demented group, even though comorbidity was similar among all three groups (Charlson Index mean scores: case = 0.7, not demented = 0.7, control = 0.5). CONCLUSIONS: Persons with Alzheimer's disease do complain of symptoms clearly related to cognitive impairment early in the course of illness, but may under-report common symptoms not suggestive of cognitive impairment, even though their comorbidity is similar to patients without dementia.

Anxiety of Alzheimer's disease: prevalence, and comorbidity.

BACKGROUND: Anxiety may be associated with psychiatric morbidity, disability, increased health care utilization, and mortality in Alzheimer's disease (AD) patients as it is in the general adult population. However, the phenomenology of anxiety symptoms in AD and its relationship to dementia progression, comorbid depression, and the presence of other problematic behaviors have not yet been examined. METHOD: Data on anxiety symptoms and their coexistence with other factors were obtained in 523 community-dwelling AD patients through interviews with their caregivers and direct physical examination. The prevalence of anxiety symptoms and their association to patient depression, other behavioral problems, gender, and age was investigated. RESULTS: Anxiety symptoms were common, occurring in 70% of subjects. Anxiety symptoms were significantly correlated with ADL impairment and other behavioral disturbances, including wandering, sexual misconduct, hallucinations, verbal threats, and physical abuse. Comorbidity of anxiety-depression was also prevalent: 54% of the sample had both anxiety and depression symptoms. ADL impairment and problem behaviors were significantly associated with comorbidity; however, the latter association was explained entirely by the presence of anxiety. CONCLUSION: Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. These results indicate the need for additional research into the phenomenology of anxiety and comorbid anxiety-depression in AD and for the development and investigation of effective assessment and treatment of anxiety in AD clinical practice.

Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Cerebral N-acetylaspartate is low in patients with multiple sclerosis and abnormal visual evoked potentials.

PURPOSE: Our purpose was to compare cerebral proton MR metabolite changes in patients with multiple sclerosis (MS) and abnormal visual evoked potentials (VEPs) with those in MS patients with normal VEPs. METHODS: Seventeen subjects with clinically definite MS were studied with VEPs and MR spectroscopic imaging. Proton MR metabolites were measured using a fast spectroscopic imaging technique called proton echo-planar spectroscopic imaging (PEPSI). Kurtzke's Expanded Disability Status Scale (EDSS) score was also ascertained for each subject to obtain a clinical rating. Twelve regions of interest within the visual pathway of the cerebrum were evaluated for levels of N-acetylaspartate (NAA), choline, creatine, and the presence or absence of MR-detectable lesions. RESULTS: PEPSI NAA values (water-normalized, CSF-corrected) were significantly lower in MS subjects with abnormal VEPs than in subjects with normal VEPs. MR-detectable lesion fractions and EDSS scores were also significantly different between the two VEP groups, but NAA comparison had a P value 100 times less than either of these measures. CONCLUSION: In patients with MS, NAA measurements in the optic pathways of the brain were sensitive to VEP abnormalities. NAA was more sensitive to VEP changes than were choline, creatine, MR-detectable lesions, and EDSS score.

Drug-induced cognitive impairment. Defining the problem and finding solutions.

Drug-induced cognitive impairment is a common cause of delirium and is frequently a confounding factor in dementia. Predisposing conditions for delirium include age, brain disease and addiction to alcohol and/or drugs. The elderly are at particular risk because of multiple diseases, multiple drug use and alterations of drug metabolism associated with age. Sedatives such as benzodiazepines have a particularly high risk of cognitive impairment. Centrally acting sympathetic antihypertensive agents, sedating antipsychotic drugs, opioids, digitalis, anti-Parkinsonian drugs, antidepressants and corticosteroids are also associated with greater risk relative to other classes of medications. Cognitive impairment due to medication may be reduced by recognition of the problem. The risk of drug-induced impairment may be minimised by strategies which optimise overall health, avoidance of unnecessary medications, and selection of medications least likely to cause delirium.

Study of Alzheimer's dementia patients with parkinsonian features.

This paper presents a study to test the hypothesis that a parkinsonian subtype of Alzheimer's disease exists. Twenty-one patients with dementia of the Alzheimer's type (DAT) and coexistent parkinsonian features were matched to 21 DAT control patients without parkinsonian signs. All subjects were drawn from 136 patients with DAT evaluated between 1980 and 1982. Items from a standardized clinical evaluation at the time of diagnosis, from continuous yearly follow-ups, and neuropathologic examination were compared to determine if qualitative differences exist between the two groups. Those with parkinsonian features had significantly shorter duration of symptoms prior to presentation, a trend toward more reports of decreased self-care, and more primitive reflexes on physical examination. While the total Folstein Mini-Mental State Exam (MMSE) scores at presentation were not significantly different, the cases showed greater impairment in language and registration subitems. During follow-up, no differences were observed in performance on MMSE and Dementia Rating Scale scores. Survival curves showed a trend toward poorer survival in the cases. Neuropathologic data were obtained on seven patients with both DAT and parkinsonian features and showed three cases with Alzheimer's disease (AD) alone and four with AD and Parkinson's disease. Four of the DAT control patients were examined neuropathologically, and all had AD without evidence of Parkinson's disease. The results provide preliminary evidence that Alzheimer's patients with parkinsonian signs are a subtype characterized by distinct neurologic signs and a more rapid course.

Characteristics of sleep disturbance in community-dwelling Alzheimer's disease patients.

This study examined the frequency, predictors, and impact of sleep problems in a population-based sample of 205 Alzheimer's disease (AD) patients. Sleeping more than usual and early morning awakenings were the most common sleep problems reported but were the least disturbing behaviors for caregivers. Night-time awakenings were less common but were most disturbing to caregivers. Using logistic regression analyses, the factors most strongly associated with night awakenings among patients were male gender, greater memory problems, and decreased functional status. Patient depression increased the risk for caregivers to rate patient sleep problems as more disturbing overall. Cluster analyses revealed three characteristic groups of patients who awakened caregivers: one group was inactive during the day but had few other behavior problems; one group had increased levels of fearfulness, fidgeting, and occasional sadness; and the third group had multiple behavior problems, including frequent episodes of sadness, fearfulness, inactivity, fidgeting, and hallucinations. These findings indicate that the nature of sleep problems in AD is multifaceted; future research on the occurrence and treatment of sleep disturbance in dementia patients should consider the patterns of individual differences that may influence its development.

Spondylolysis associated with Arnold-Chiari malformation and syringomyelia. A report of two cases.

STUDY DESIGN: This is a report of two cases. OBJECTIVE: To document the occurrence and association of spondylolysis and Arnold-Chiari malformation Type I. SUMMARY OF BACKGROUND DATA: The association of spinal dysraphism has been reported with Arnold-Chiari Type II, but not with Arnold-Chiari Type I. METHODS: The senior author was involved in the care of these patients. All medical records, laboratory and radiologic investigations, and related literature were reviewed. RESULTS: The presence of cephalic and caudal neuropore maldevelopment may be present in various combinations. The presence of spondylolysis, with or without spina bifida occulta, associated with Arnold-Chiari malformation type I and syringohydromyelia, is demonstrated. CONCLUSIONS: In some patients, the presence of spondylolysis may represent a congenital anomaly and may be associated with cephalic neuropore maldevelopment, such as cerebromedullary malformation syndrome (i.e., Arnold-Chiari malformation Type I).

Laparoscopic adrenalectomy is superior to an open approach to treat primary hyperaldosteronism.

We reviewed our institutional experience with primary hyperaldosteronism to compare clinical outcomes after laparoscopic versus open adrenalectomy. All patients surgically treated for primary hyperaldosteronism from 1988 through 1999 are included in this study. Patients were assigned to either the LA (laparoscopic) or OA (open) group depending on the initial surgical approach selected for treatment. Records were reviewed to determine demographics, operative results, and complications. Twenty-four patients were surgically treated for primary hyperaldosteronism. There were no significant differences between groups with respect to age, weight, number of preoperative antihypertensive medications, or preoperative potassium level. The results of adrenalectomy with respect to number of postoperative antihypertensive medications or serum potassium level were also similar. Operative times were not significantly different (191 +/- 53 minutes for OA and 205 +/- 88 minutes for LA) between groups, but four LA patients were converted to OA. Estimated blood loss was 401 +/- 513 cm3 for OA and 127 +/- 131 cm3 for LA (P = 0.07). Hospital length of stay was 6.7 +/- 3.7 days for OA and 3.3 +/- 2.7 days for LA (P = 0.02). Complications were nine for OA and three for LA (P = 0.001 by Pearson's Chi square). LA is similar to OA in the treatment of primary hyperaldosteronism. The significantly fewer complications and shorter length of hospital stay associated with LA makes the laparoscopic approach the preferred method for treating primary hyperaldosteronism.