The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Comparison of Alzheimer's disease risk factors in white and African American families.

The associations between alcohol, smoking, and head injury and the risk of AD in 443 African American and 2,336 white participants in the MIRAGE Study were evaluated. Alcohol had a modest protective effect in whites (odds ratio [OR] = 0.82, 95% CI = 0.68 to 0.99), with a similar trend in African Americans (OR = 0.88, 95% CI = 0.54 to 1.4). Head trauma increased the risk of AD in whites (OR = 2.3, 95% CI = 1.8 to 3.0) and African Americans (OR = 2.9, 95% CI = 1.2 to 7.0). Smoking was not associated with AD risk in whites (OR = 0.88, 95% CI = 0.73 to 1.1) or African Americans (OR = 1.0, 95% CI = 0.69 to 1.5). These risks were similar across subsets stratified by the presence or absence of the APOE epsilon4 allele.

Firearm presence in households of patients with Alzheimer's disease and related dementias.

OBJECTIVE: Attention has recently been drawn to the potential dangers of firearm use among patients with dementia. However, little is known about the actual prevalence of firearms in households with demented family members. This study seeks to determine the prevalence and loaded status of firearms in households with a demented family member in a sample of outpatients at a University memory disorders clinic. DESIGN: Utilizing a cross-sectional design, subjects underwent a structured NINCDS-ADRDA criteria comprehensive evaluation to assess dementia and were also administered a questionnaire to assess level of mood disturbance. Family members were administered a behavioral checklist and surveyed about the number and loaded status of firearms in the patient's household. SETTING: The study took place in an outpatient Medical University memory disorders clinic in the Southern United States. PATIENTS: Subjects were 106 consecutive outpatients referred for symptoms suggestive of dementia. MAIN OUTCOME MEASURES: Firearm presence was coded as "present," "not present," and "unsure." In cases where firearms were present, the number and loaded status were collected. Other outcome measures included the Clinical Dementia Rating of each patient, the Yesavage Mood Inventory, and the Revised Memory and Behavior Problems Checklist. RESULTS: A high prevalence of firearm prevalence in households with demented family members was revealed (60.4%). Gun ownership was equally prevalent in households regardless of the severity of the dementia (chi-square, P = .426), severity of behavioral disturbance (ANOVA P = .88), or depressive symptoms (ANOVA P = .37). In households with firearms, 44.6% of the families reported that the guns were kept loaded; 38% reported that they did not know whether the guns were loaded. Only 16.9% of the families reported that guns were maintained in an unloaded state. CONCLUSIONS: This study suggests that many family members living in households in which there are demented patients do not take appropriate action to remove or unload firearms in their households, regardless of the severity of dementia, behavioral disturbance, or depression. These findings suggest that clinicians need to ask families specifically about the presence of firearms and advocate for their removal.

The geographic variation in stroke incidence in two areas of the southeastern stroke belt: the Anderson and Pee Dee Stroke Study.

BACKGROUND AND PURPOSE: South Carolina and the southeastern United States have maintained the highest stroke mortality in the country. The Anderson and Pee Dee Stroke Study is an assessment of cerebrovascular disease incidence in 2 geographically defined communities in the stroke belt. METHODS: Strokes were identified in the Anderson and Pee Dee areas of South Carolina. All hospitalized and out-of-hospital deaths occurring during 1990 among the residents of these 2 areas were included. Strokes were classified by an independent panel of neurologists using a standard protocol that included specific criteria for stroke and subtypes. RESULTS: The overall age-adjusted stroke incidence rates (per 100 000 population) were significantly higher in the Pee Dee population (293.1) compared with Anderson (211.2). The geographic differences were more dramatic in the younger age groups of 35 to 64 years. Likewise, incidence rates for blacks were nearly twice the rates for whites. The rates in the Pee Dee were higher than the rates from other studies in the United States and other parts of the world. Although the stroke subtypes did not vary between the 2 regions, race-sex differences were identified. CONCLUSIONS: High stroke incidence and disease rates persist for all 4 race-sex groups in the Southeast and reflect similar risks as mortality rates. However, geographic variability in stroke rates suggests that the pattern of disease in the region is not so much a "belt" of increased stroke in contiguous areas but rather more a "necklace" of different levels of risk. These results should be useful in the identification of factors associated with this geographic enigma.

Effectiveness of a continuum of care using brief and partial hospitalization for agitated dementia patients.

OBJECTIVE: A behavioral intensive care unit was originally designed as a 21-day inpatient program for treating agitation among demented patients, one of the most common behavioral disorders in this group. Due to the need to dramatically reduce length of stay and create alternative care environments, the original model was modified into an integrated continuum of care blending inpatient and outpatient care and partial hospitalization that reduced hospitalization from 21 to an average of seven days. This quasiexperimental study compared the effectiveness of the inpatient and continuum-of-care programs and conducted cost analyses. METHODS: Subjects were inpatients diagnosed with both dementia and agitation. Outcomes of 68 patients treated in the inpatient program were compared with those of 110 patients treated in the continuum of care. The primary outcome measure was patients' score on the Cohen-Mansfield Agitation Inventory, which provides a total agitation score and scores on three factors describing agitated behavior--physically aggressive behavior, verbally aggressive behavior, and nonaggressive behavior. RESULTS: A statistically significant reduction in agitation was found for patients treated in both programs, with no significant difference in outcome between programs. Patients in both programs showed significant improvements in physical aggression, verbal aggression, and nonaggressive behavior. The cost-effectiveness analysis revealed clear advantages for the continuum-of-care program, especially in the area of aggressive behaviors. CONCLUSIONS: The data suggest that the restructured program is an effective and economically feasible intervention.

Unawareness of cognitive deficit in Alzheimer disease and related dementias.

The objective of this study was to determine whether unawareness of cognitive deficit is disease-specific. One hundred thirty-two patients were studied, grouped according to diagnosis of definite or probable Alzheimer disease, vascular dementia, geropsychiatric control, or geriatric control. Diagnosis was the independent variable, and unawareness of cognitive deficit was the dependent variable. The Mini-Mental State Examination score was used as a dementia severity covariate. Analysis of covariance was significant (F = 8.0, p < 0.0001). Follow-up mean comparisons showed the Alzheimer disease group to have significantly greater unawareness of cognitive deficit than all other groups. The vascular dementia group had significantly greater unawareness of cognitive deficit than the two control groups. These results support the premise that, independent of dementia severity, unawareness of cognitive deficit is disease specific.

Neuropsychological features of diffuse Lewy body disease.

A case of a 60-year-old man with biopsy-proven diffuse Lewy body disease was presented with clinical and serial neuropsychological data. Findings showed a rapid decline over a 2-year period characterized by an atypical degenerative dementia, including a global mental decline with preserved orientation, profound perceptual deficits, and no specific relative progressive memory impairment. Few extrapyramidal signs were noted, but subtle visual hallucinations and vivid nightmares occurred throughout the course. He underwent an experimental trial of tacrine, but showed an adverse reaction. Of the few detailed neurocognitive case descriptions of this disease found in the literature, this article highlights the unique variability and clinical manifestations that differentiate this disorder from the dementia of the Alzheimer's type.

Prior head injury in male veterans with borderline personality disorder.

This study evaluated the relationship between traumatic brain injury (TBI) and borderline personality disorder (BPD). Forty-three males with BPD were compared with 49 age- and sex-matched controls with other psychiatric diagnoses. The occurrence of TBI was identified by chart review. Head injury was identified in 42% of patients meeting criteria for BPD but in only 4% of controls (p < .001). All patients but one had sustained a TBI prior to the diagnosis of BPD. The prevalence of TBI is higher in subjects with BPD than in controls. Since TBI occurred prior to the full expression of the BPD clinical syndrome, TBI appears to be a cause rather than the result of BPD.

The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort.

OBJECTIVE: To evaluate the interval between the onset of detectable cognitive impairment and clinical diagnosis in individuals with probable Alzheimer's disease (AD), and to identify the pattern of the earliest changes in cognition in probable AD. DESIGN: Longitudinal follow-up of a community-based cohort sample. In 1976 through 1978, a screening neuropsychological examination was administered to Framingham Study participants. These subjects were then followed up prospectively for development of probable AD for up to 13 years. SETTING: This study was conducted at a community-based center for epidemiologic research. PARTICIPANTS: The surveillance sample consisted of 1045 participants in the Framingham Study aged 65 to 88 years who were free of dementia at the time of the neuropsychological screening examination. MAIN OUTCOME MEASURES: Scores on a group of neuropsychological tests were entered into a series of age- and education-adjusted multiple regression procedures, with the presence or absence of probable AD as the outcome variable. RESULTS: Considered individually, most of the screening neuropsychological measures were significantly related to later AD diagnosis. When stepwise regression procedures were employed, only measures of verbal memory and immediate auditory attention span remained significantly related to AD diagnosis. Of note, subjects later diagnosed with probable AD performed at higher levels than normal subjects on the Digit Span test at initial screening. Regression results were essentially unchanged even when the AD sample was restricted to those individuals for whom the screening examination preceded the clinical onset of dementia by 7 years or more. CONCLUSIONS: These findings support previous contentions that a "preclinical phase" of detectable cognitive deficits can precede the clinical diagnosis of probable AD by many years, and they also support the hypothesis that problems with secondary verbal memory are among the first signs of AD.

Clinical expression and diagnosis of atypical cortical degenerative syndromes.

Atypical cortical degenerative syndromes of the non-Alzheimer's disease type are becoming increasingly recognized in the literature. Three cases consisting of primary progressive aphasia, posterior cortical atrophy, and frontal lobe dementia of the non-Alzheimer's type are presented to replicate and extend emerging literature. Detailed clinical description and neuropsychological data, coupled with confirmatory neurofunctional imaging, are presented to provide empirical support that specific inclusion and exclusion criteria can be applied to clinically diagnosis atypical degenerative cortical dementias.

Neurobehavioral study of borderline personality disorder.

The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup.

Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham Study.

OBJECTIVE: To determine the incidence of dementia and Alzheimer's disease (AD) in a general population sample. BACKGROUND: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. METHODS: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. RESULTS: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. CONCLUSIONS: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years.

Sleep disorders with aging: evaluation and treatment.

Sleep disorders are especially common among elderly patients and may be the result of psychiatric illness, a medical problem, poor sleep habits, or a primary sleep disorder. Because a sleep complaint (especially insomnia) is only a symptom, the physician must undertake a careful evaluation in an attempt to identify a specific treatable cause. Although some patients may require referral to a psychiatrist or sleep disorders clinic, many patients may benefit from behavioral strategies, such as improved sleep hygiene. In general, hypnotics should be prescribed for only a limited period of time and should be combined with other therapeutic approaches in patients with chronic insomnia.

Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study.

We determined the prevalence of dementia and probable senile dementia of the Alzheimer type (SDAT) for biennial Exam 17 of the Framingham cohort (1982/1983). The prevalence of dementia was 30.5/1,000 for men and 48.2/1,000 for women and increased with advancing age. Cases of probable SDAT constituted 55.6% of all dementia cases. THe prevalence of SDAT was 11.7/1,000 for men and 30.1/1,000 for women and also increased with advancing age. Prevalence of dementia and probable SDAT were greater for women than men. The female:male ratio of prevalence for cohort members 75 years of age and older was 1.8 for all cases of dementia and 2.8 for cases of probable SDAT.

Preserved visual imagery and categorization in a case of associative visual agnosia.

A patient with associative visual agnosia secondary to a penetrating bitemporooccipital lesion remained able to draw complex objects from memory but could not subsequently recognize his sketches. His retained ability to copy and draw briefly exposed objects indicates that this is not a problem of visual perception. On tasks of categorization, mental imagery, drawing, and object decision, he demonstrates many instances of preserved visual semantic memories and imagery despite a sense of unfamiliarity with the visual stimuli. We infer a preserved ability to derive internal visual images from semantic memory. Cues may help him visualize the named object, which then serves as a model for comparison with the actual stimulus. However, his adequate visual perception and mental visual imagery, even when assisted by cues, are still insufficient to correct fully his difficulty in recognizing objects. Unique to his case is an inability to match the representation of stimulus objects with his intact internal image of the same object. Deficient lateral inhibition between neural representations of similar objects may be responsible.

Pharmacotherapy for akinesia following anterior communicating artery aneurysm hemorrhage.

The dopamine system may be involved in three situations: the nigral projection to the basal ganglia, the mesocortical projection to the anterior cingulate gyrus, or the medial forebrain bundle projection to cortical and limbic sites. Because of the close association of dopamine systems with the known neurological syndromes of akinesia, we elected to treat a patient with akinesia due to rupture of anterior communicating artery (ACA) aneurysm with the dopamine agonist, bromocriptine. This case has important implications for the understanding of brain/behavior relationships as well as for the development of new therapies for patients who have sustained neurological injury.

Depressive symptoms following stroke.

OBJECTIVE: The primary purpose of this study was to assess the relation of lesion location to mood and vegetative disturbance following stroke. METHOD: Fifty-two inpatients and outpatients who had had single, unilateral strokes were included. Patients with past CNS or psychiatric disorders were excluded. A modified Visual Analogue Dysphoria Scale was used to allow the inclusion of all but the most impaired aphasic patients. Sleep and eating disturbances were measured by using both self-report and nursing assessments. Location of lesions was determined by CT scan and classified according to three dimensions: right-left, dorsal-ventral, and frontal-nonfrontal. RESULTS: On measures of dysphoric mood and sleep disturbance, results indicated significant three-way interactions among the three lesion dimensions. No differences were found with regard to eating disturbance. Greater dysphoria and sleep disturbance were found in subjects with left parietal/occipital, left inferior frontal, right superior frontal, and right temporal lesions than in subjects with lesions in other locations. Depressive symptoms were not associated with functional impairment as measured by activities of daily living, motor strength, or severity of aphasia. CONCLUSIONS: These results support the hypothesis that lesion location is a valid and significant factor in the mixture of influences which may result in a dysphoric mood state following stroke. The relation between the site of the lesion and subsequent depressive symptoms, however, may be more complex than has been reported previously.

Pharmacotherapy for aphasia.

Selected features of aphasia may reflect disruption of specific neurotransmitter systems. Pharmacotherapy focused on these aphasic symptoms may improve language performance following stroke. We attempted to restore speech fluency in a patient with long-standing transcortical motor aphasia by treating his symptoms of hesitancy and impaired initiation of speech with bromocriptine. During therapy his language performance improved substantially, due to reduced latency of response, decreased paraphasias, and increased naming ability. After cessation of drug therapy his language returned to baseline.