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BACKGROUND: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). METHODS: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65-99 years) from 2003 to 2007. RESULTS: Among 318 participants, the mean age was 73.5 +/- 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10-20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (< or =20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (< or =20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2-4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1-6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.

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OBJECTIVE: Homebound elderly are at increased risk for micronutrient deficiencies and nutritional status in this population has not been adequately described. There is evidence for beneficial effects of multivitamin use and a greater understanding of their nutritional contribution could identify behaviors that may help alleviate excess chronic disease. The purpose of this analysis is to investigate, in a racially diverse group of homebound elders, the association of multivitamin use with measures of plasma B vitamin concentrations. DESIGN: We examined the cross-sectional association between multivitamin use and plasma concentrations of B vitamins and homocysteine in 236 white and 182 black homebound elders (65-99y). Dietary intake was assessed and demographic and health information was ascertained. RESULTS: White and black elders had a high prevalence of dietary intakes below the Estimated Average Requirement for folate (38.1 and 40.7%), vitamin B6 (16.9 and 19.2%.), and vitamin B12 (3 and 3.9%) respectively. Multivitamin use was associated with higher mean plasma B vitamin concentrations in each group. In whites, multivitamin users had higher concentrations of vitamin B6 (64.6 vs. 32.4 nmol/L; p < 0.001), vitamin B12 (398 vs. 324 pmol/L;p < 0.001) and folate (39.4 vs. 30.4 nmol/L;p < 0.001). Black multivitamin users had higher concentrations of vitamin B6 (53.7 vs. 29.5 nmol/L; p < 0.001), B12 (427 vs. 372 pmol/L; p < 0.05) and folate (35.7 vs. 25.4 nmol/L; < 0.001) than non-users. CONCLUSIONS: Multivitamin supplementation was associated with higher mean plasma concentrations of vitamins B6, B12, and folate and lower prevalence of low plasma B vitamin status in a biracial homebound elderly.

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Especially in outpatient settings, dementia is still an underdiagnosed syndrome. The Micro-Mental Test has been developed as a short version of the Mini-Mental-Status Examination (MMSE). We examined the reliability and diagnostic validity of a German version (Mikro-Mental Test). We administered the MMSE and the German version of the Micro-Mental Test to 20 inpatients of a geriatric psychiatry hospital (mean age 74.8+/-8.1 years), 55 patients from a cognitive clinic (mean age 71.9+/-9.1 years), and 27 healthy older adults (mean age 68.5+/-4.1 years). Diagnoses made by an experienced psychiatrist according to ICD-10 criteria served as external criteria. The mean duration for testing with the Micro-Mental Test was 8 min, and with the MMSE 15 min. Test-retest analyses showed satisfactory reliability. With regard to sensitivity and specificity, we found comparable diagnostic validity for the MMSE and the Micro-Mental Test. We suggest that, due to its brevity and diagnostic validity, the Micro-Mental Test is a useful tool for dementia screening in an outpatient setting.

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PURPOSE: To investigate the prevalence of, and potential risk factors for, emotional distress among patients with retinal disease. DESIGN: Cross-sectional study. METHODS: Cases consisted of 86 consecutive patients at Wilmer Eye Institute Retinal Vascular Center. Fifty-one controls with normal visual acuity and no known ocular disease were frequency-matched to the cases by age, sex, and race. Subjects were interviewed using the Community Disability Scale, a functional status questionnaire, and the General Health Questionnaire, a questionnaire assessing emotional distress. RESULTS: The prevalence of probable (General Health Questionnaire score 4 or greater and less than 10) or definite (General Health Questionnaire score 10 or greater) emotional distress was 59.3% among ophthalmic patients and 2.0% among controls. There were significant relationships between emotional distress, as assessed by General Health Questionnaire score, and degree of 1) visual impairment, as assessed by weighted bilateral average logarithm of minimal angle of resolution (logMAR), and 2) functional impairment, as assessed by Community Disability Scale score (P =.001). Univariate analyses identified significant predictors of emotional distress: shorter duration of ocular disease (P =.019), worse visual acuity (P =.001), increased systemic comorbidities (P =.001), and increased functional impairment (P <.001). Multiple regression analysis demonstrates that worse visual acuity, increased systemic comorbidities, and shorter duration of ocular disease each explain over 10% of the variability in General Health Questionnaire score (r(2) = 0.15, 0.12, and 0.11, respectively). Addition of Community Disability Scale score to the regression model eliminates the significance of visual acuity and systemic comorbidities; Community Disability Scale score explains nearly 30% of the variability in emotional distress, as assessed by General Health Questionnaire score (r(2) = 0.29). CONCLUSIONS: Emotional distress is prevalent among patients with retinal disease; potential risk factors for emotional distress among such patients include shorter duration of ocular disease, worse visual acuity, increased systemic comorbidities, and increased functional impairment.

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PURPOSE: To investigate the prevalence and phenomenologic nature of visual hallucinations among patients with retinal disease and to investigate whether presence of hallucinations is a significant predictor of functional status, quality of life, and/or emotional distress after adjusting for visual acuity. DESIGN: Cross-sectional study. METHODS: Eighty-six consecutive patients at the Wilmer Ophthalmologic Institute Retinal Vascular Center were interviewed using the Sickness Impact Profile, Community Disability Scale, General Health Questionnaire, Visual Phenomena Interview, Eysenck Personality Questionnaire, and Telephone Interview for Cognitive Status. RESULTS: The prevalence of visual hallucinations was 15.1%. Most were formed hallucinations in clear consciousness that lasted for seconds to minutes. The majority of patients had been experiencing visual hallucinations for less than 1 year (61.5%) or for 1 to 2 years (23.1%). Only two of the 13 patients with hallucinations had informed a physician of their hallucinations. Univariate analyses revealed that variables significantly associated with experiencing hallucinations were female sex, worse visual acuity, bilateral visual impairment, emotional distress, decreased functional status, and decreased quality of life. Regression analysis demonstrated that among patients with relatively good vision, those who experienced hallucinations were more emotionally distressed and had a lower quality of life than patients without hallucinations. CONCLUSIONS: Visual hallucinations among patients with retinal disease are common, underdiagnosed, and not associated with cognitive deficits, abnormal personality traits, or a family or personal history of psychiatric morbidity. Among patients with relatively good vision, hallucinations are associated with increased emotional distress and decreased quality of life.

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OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.

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OBJECTIVE: The purpose of this pilot study was to gain information about attitudes of individuals with bipolar disorder and their spouses toward some of the ethical and social issues arising from rapidly advancing genetic research on bipolar disorder. METHOD: Patients with bipolar disorder and their unaffected spouses were asked to answer questionnaires assessing their knowledge and attitudes about treatment response rates for bipolar disorder, probability of inheritance, genetic testing, disclosure of genetic information, abortion, marriage, and child-bearing. RESULTS: The overwhelming majority of the patients and spouses said that they would take advantage of genetic tests for bipolar disorder if such tests were to become available. Most patients and spouses agreed that the benefits of knowing whether one carries a gene for bipolar disorder would outweigh the risks. The decisive majority of respondents also felt that they would not abort a fetus that carried a gene for bipolar disorder. Furthermore, most patients and spouses agreed that the knowledge that one of them carried a gene for bipolar disorder would not have deterred them from marriage or childbearing. CONCLUSIONS: The results of this study suggest that most individuals believe that they would benefit from the use of genetic testing for bipolar disorder if it were to become available. Follow-up studies using a broader patient sample and nonclinical control groups would be useful in further evaluating the issues addressed in this pilot study.

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BACKGROUND: The purpose of this analysis was to examine: (1) the prevalence of psychiatric disorders among disabled people, using seven different measures of disability; (2) variation in disability between and within psychiatric diagnostic categories; and (3) relationship of diagnosis and disability to health service utilization. METHOD: Data were drawn from Phase I and Phase II of the Eastern Baltimore Mental Health Survey, part of the Epidemiologic Catchment Area Program (ECA) conducted in 1980-1 to survey mental morbidity within the adult population. A total of 810 individuals received both a household interview and a standardized clinical psychiatric evaluation. Estimated prevalence rates were computed using appropriate survey sampling weights. RESULTS: Prevalence of disability ranged from 2.5 to 19.5%, varying with specific disability measure. Among those classified as disabled by any of the measures examined, 56 to 92% had a psychiatric disorder and serious chronic medical conditions were present in the majority of these cases (54 to 78%). Disability was expressed differently among the various diagnostic groups. Diagnostic category and disability were significant independent predictors of medical service utilization and receipt of disability payments. CONCLUSIONS: The majority of disabled adults living in the community have diagnosable psychiatric disorders, with the majority of these individuals suffering from significant chronic medical conditions as well, thus making co-morbidity the norm.

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Somatization, broadly defined as the presentation of one or more medically unexplained somatic symptoms, refers both to the presentation of somatic symptoms in diagnosable psychiatric disorders such as major depression or anxiety as well as to the presentation of such symptoms in somatoform disorders. Although no comparative data exist, somatization is considered by many clinical investigators to be more common among Chinese than Caucasian patients, but it is unclear if this occurs because somatoform disorders are more prevalent among the Chinese or because Chinese patients with major depression or anxiety more often present with somatic complaints. We examined 85 consecutive Chinese American and 85 consecutive Caucasian American patients referred for psychiatric consultation and found the following: a) True somatization was significantly more common among Chinese American patients referred for psychiatric consultation; b) The somatoform symptom profiles of the two cohorts were different: Chinese American somatizers complained predominantly of cardiopulmonary and vestibular symptoms, whereas their Caucasian counterparts had symptoms that corresponded well with the categories listed in DSM-IV; c) In both cohorts of somatizers, a concurrent psychiatric disorder, most commonly major depression, was almost always present; and d) Among the Chinese American somatizers, pseudoneurological symptoms occurred most commonly in the form of abnormal sensations, whereas abnormal motor functions were more common among Caucasian Americans. Implications of the findings with respect to pathogenesis, treatment, and classification of somatization are discussed.

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Dementia as a syndrome must be differentiated from nondementing conditions. Dementia itself must also be differentiated as to cause, as in certain cases reversible conditions may be responsible. This article examines the clinical process of such differentiation, providing a decision free for diagnosis and a summarizing algorithm for thinking through individual cases, with a focus on the most frequent cause of dementia, Alzheimer's disease. Also outlined are the stages of Alzheimer's disease, with the admonition that variations from the expected progression may represent a dementia diagnosis other than Alzheimer's disease or the co-occurrence of some other contributing factors.

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Assessment of capacity to give informed consent in the general hospital setting usually rests on a clinical judgment made of a patient's understanding and appreciation of his or her illness, a process limited by its subjective nature, interexaminer variability, and relative deficiency of quantitative instruments available to provide collateral information. Inasmuch as identification of associated variables could strengthen this process, this study examines the association of cognitive functions to the capacity to give informed consent. Over a one-year period, 65 patients were evaluated independent of medical or psychiatric diagnoses. The study population consisted of medical and neurology inpatients seen for neuropsychiatric evaluation. All evaluations included assessment of capacity to give informed consent as it related to the reason for the admission to the hospital, followed by administration of the Hopkins Competency Assessment Test, the Mini-Mental Status Examination, the Trail-Making Test, Parts A and B, and the Executive Interview. Of 65 patients, 34 were excluded based on preset criteria. The remaining patients were assigned to either a "competent" or "noncompetent" group based on clinical evaluation. Number of patients, gender, and handedness distributions between groups were similar. The groups did not differ significantly in terms of age or education. Significant between-group differences were found on an empirical measure of competency, a general mental state measure, and on measures of attentional and executive cognitive functions. An analysis of classification rates indicated that a measure of executive cognitive functioning (Executive Interview) had the best sensitivity and specificity in correctly classifying competent and noncompetent patients. The results of this study support the association between the capacity to give informed consent in the hospital setting and measures of cognitive functioning, suggesting that utilization of cognitive function measures may strengthen the competency assessment process.

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As part of the NIMH Genetics Initiative Alzheimer's Disease (AD) Study Group, a brief structured telephone interview to distinguish individuals with normal cognitive functioning from those with changes in cognition and daily functioning suggestive of early AD was developed. The Structured Telephone Interview for Dementia Assessment (STIDA), yields a dementia score between 0 and 81 (higher scores indicating greater impairment). Subscales corresponding to the subscales of the Clinical Dementia Rating Scale (CDR) can be derived. The STIDA performed well as a screening instrument for mildly demented individuals. When a score of 10 or more (based on informant interview and subject testing) was used to identify mildly impaired individuals, the STIDA had a sensitivity of .93 and a specificity of .92 for a clinician-derived CDR of 0.5 or more. The STIDA was also capable of accurately assessing the level of dementia. STIDA-derived CDR ratings agreed with clinician-derived CDR scores in 23 of 28 cases, corresponding to an unweighted kappa of.71 and a weighted kappa of.81. A much-abbreviated short STIDA that could be administered directly to the subject was able to detect possible impairment with a sensitivity of .93 and a specificity of.77. These results suggest that the short STIDA provides a sensitive and fairly specific telephone screen for dementia, and that the full STIDA, consisting of an interview with a knowledgeable informant and subject testing, approximates the success of a face-to-face clinical interview, and provides reliable and valid screening and staging of dementia over the telephone.

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One hundred patients with clinically diagnosed Huntington's disease (HD) were randomized to either idebenone, an antioxidant and enhancer of oxidative metabolism, or placebo, in a 1-year, double-blind, parallel-group study aimed at slowing the rate of progression of the disease. Ninety-one patients completed the study. There were no significant differences between groups on the primary outcome measures of the Huntington's Disease Activities of Daily Living Scale (ADL-an index of functional status) and the Quantified Neurologic Examination (QNE). Sample size calculations based on progression of the ADL and QNE in this study group revealed that a larger study group is necessary to detect any differences less than an almost complete halting of the disease. This argues for multicenter efforts for future therapeutic trials in HD.

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We determined the apolipoprotein E4 (apoE) genotype in 12 cases of autopsy-confirmed hippocampal sclerosis dementia (HSD), a disorder characterized pathologically by neuronal degeneration, predominantly of temporal lobe structures, without senile plaques or neurofibrillary tangles. The frequency of the apoE4 allele in HSD was 12.5%, similar to that of a control population and significantly different from the approximately 40% found in Alzheimer's disease (AD) (P < 0.001). These observations suggest that apoE4 is not a risk factor for HSD.

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Neuropathological examination confirmed the clinical diagnosis of possible or probable Alzheimer disease (AD) in 90 of the first 100 patients who came to autopsy at the Johns Hopkins Alzheimer's Disease Research Center. In 10 cases, postmortem brain examination did not confirm AD but revealed variable patterns of neuronal loss in neocortex and limbic structures without amyloid deposits. The most common pattern of degeneration was relatively isolated hippocampal sclerosis (HS). Despite the finding that the 10 patients with non-AD neuropathology were ill for less time and were less cognitively impaired at study entry than those patients with definite AD, they had shorter survival times and showed equal behavioral disturbance at study entry (on a standardized measure). The clinical case reports included here suggest early and progressive prominent behavioral disturbance and other indexes of rapid illness progression in three of the four HS patients and two other non-AD patients. We conclude that the criteria of the National Institute of Neurological Disorders and Stroke/Alzheimer Disease and Related Disorders Association for possible or probable AD are highly accurate and that misdiagnosis is most likely to occur early in the course of illness and in patients with prominent behavioral disturbance or other atypical features.

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OBJECTIVE: To evaluate the efficacy of a dementia care program to reduce behavior disorders in nursing home patients with dementia. DESIGN: Randomized controlled clinical trial with 6-month follow-up. SETTING: A 250-bed community nursing home. PATIENTS: The nursing home was screened to identify patients with dementia and behavior disorders. A total of 118 patients were eligible for randomization. Of these, 89 (75.4%) were randomized, and 81 of these (91.0%) completed the trial. INTERVENTION: The A.G.E. dementia care program consisted of Activities, Guidelines for psychotropic medications, and Educational rounds. The control treatment was usual nursing home care. MEASUREMENTS: Behavior disorders, antipsychotic drug and physical restraint use, patient activity levels, and cognitive and functional status. RESULTS: After 6 months, 12 of 42 (28.6%) intervention patients exhibited behavior disorders compared with 20 of 39 (51.3%) controls (OR = 0.38; 95% CI [0.15, 0.95]; P = .037). Controls were more than twice as likely to receive antipsychotics (OR = 2.55, 95% CI [0.96, 6.76]; P < .056), to be restrained during activity times (OR = 2.98, 95% CI [1.10, 8.04]; P < .028), and to be restrained on nursing units (OR = 2.14, 95% CI [0.9, 5.3]; P < .10). Intervention patients were much more likely to participate in activities (OR = 13.71; 95% CI [4.51, 41.73]; P = .001). CONCLUSIONS: The A.G.E. program reduces the prevalence of behavior disorders and the use of antipsychotic drugs and restraints. It is practical, feasible, and appears to improve the lives of patients with dementia in nursing homes.

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OBJECTIVES: To detect cases of Alzheimer's disease (AD) in a large population of twins living throughout the United States and to examine concordance for AD in twins as a function of age and genotype for apolipoprotein E (APOE). SETTING: Nationwide survey. DESIGN: Multistage screening and field evaluation beginning with two telephone interviews and culminating with laboratory tests, longitudinal neuropsychological measures, physician examination, and diagnostic consensus among experts. PARTICIPANTS: Membership in 1990-1991 of intact pairs in the National Academy of Sciences--National Research Council Registry of veteran twins, then aged 62 to 73 years. MAIN OUTCOME MEASURES: Completeness of case detection was examined in collateral studies. Zygosity and APOE genotypes were determined by restriction mapping. Concordance was calculated by the proband method. RESULTS: Ninety subjects who screened positively for AD were studied in person, and 60 whose differential diagnoses included AD were followed up, as were their co-twins. Sensitivity of screening was estimated at greater than 99%, but 24% of subjects refused participation after initial screening. Seven of 38 diagnoses of AD have been confirmed at autopsy, and 31 other subjects eventually met criteria for probable or possible AD (prevalence estimate, 0.42%, 95% confidence interval, 0.29% to 0.56%), with good interrater reliability (intraclass r = .86). Excluding one discordant pair with unknown zygosity, concordance rates were 21.1% (4/19) for monozygotic and 11.1% (2/18) for dizygotic probands. Concordance was 50% for twins sharing the epsilon 4/epsilon 4 genotype at APOE, but there were no affected co-twins of 15 probands with onset before age 70 years, no epsilon 4 allele, and no family history of AD. The mean (SD) period of discordance in the latter pairs was 11.3 (3.3) years. CONCLUSIONS: The multistage case-detection approach achieved reliable and valid diagnoses of AD with high apparent sensitivity but substantial attrition after initial screening. Genetic influences in AD at this age are limited, except among homozygotes for allele epsilon 4 at APOE. Subjects with early-onset AD who lack the epsilon 4 allele are not rare, and their condition appears to have little genetic influence. They should be ideal for studies on environmental cause of AD.

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Several case-control studies have reported head injury to be more common among patients with Alzheimer's disease (AD) than healthy elderly controls. The present study sought to determine whether milder head injury is also a risk factor for AD. Furthermore, it was hypothesized that head injury would be more common among AD patients without a genetic risk for the disease. History of head injury in 68 consecutive cases of probable or definite AD and 34 non-demented control subjects was ascertained from their spouses. Head injury was reported in 20 of the AD patients (29%), and in only one control subject (2.9%) (odds ratio = 13.75). Twenty per cent of the familial and 43.5% of the sporadic AD cases reportedly had a premorbid head injury (odds ratio = 3.08). Head injury had no effect on age of dementia onset. The results indicate that head trauma may be a predisposing factor to AD, particularly in the absence of a clear genetic contribution.

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We reviewed the records of 210 patients in the Johns Hopkins Alzheimer's Disease Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical features and progression of the disease. We compared patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a significantly shorter duration of illness at study entry. Even after controlling for this difference, the NSAID group performed better on the Mini-Mental State Examination, Boston Naming Test, and the delayed condition of the Benton Visual Retention Test. Furthermore, analysis of longitudinal changes over 1 year revealed less decline among NSAID patients than among non-NSAID patients on measures of verbal fluency, spatial recognition, and orientation. These findings support other recent studies suggesting that NSAIDs may serve a protective role in Alzheimer's disease.

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