Anticholinergic/Sedative Drug Burden and Subjective Cognitive Decline in Older Adults at Risk of Alzheimer's Disease.

BACKGROUND: Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), has been linked to cognitive impairment in older adults. Subjective cognitive decline (SCD) may be among the first symptoms patients with Alzheimer's disease (AD) experience. We examined whether DBI values are associated with SCD in older adults at risk of AD. We hypothesized that increased DBI would be associated with greater SCD at older ages. METHOD: Two-hundred-six community-dwelling, English-speaking adults (age = 65 ± 9 years) at risk of AD (42% apolipoprotein ε4 carriers; 78% with AD family history) were administered a single question to ascertain SCD: "Do you feel like your memory is becoming worse?" Response options were "No"; "Yes, but this does not worry me"; and "Yes, this worries me." DBI values were derived from self-reported medication regimens using older adult dosing recommendations. Adjusting for relevant covariates (comorbidities and polypharmacy), we examined independent effects of age and DBI on SCD, as well as the moderating effect of age on the DBI-SCD association at mean ± 1 SD of age. RESULTS: Both SCD and anticholinergic/sedative drug burden were prevalent. Greater drug burden was predictive of SCD severity, but age alone was not. A significant DBI*Age interaction emerged with greater drug burden corresponding to more severe SCD among individuals age 65 and older. CONCLUSION: Anticholinergic/sedative drug exposure was associated with greater SCD in adults 65 and older at risk for AD. Longitudinal research is needed to understand if this relationship is a pre-clinical marker of neurodegenerative disease and predictive of future cognitive decline.

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers.

OBJECTIVE: The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI. METHODS: Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65-85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes. RESULTS: At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1-5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1-5 scores were significant predictors of MCI conversion. CONCLUSIONS: Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

Differential 5-year brain atrophy rates in cognitively declining and stable APOE-ε4 elders.

OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for late-onset Alzheimer's disease. Many ε4 carriers, however, never develop Alzheimer's disease. The purpose of this study is to characterize the variability in phenotypic expression of the ε4 allele, as measured by the longitudinal trajectory of cognitive test scores and MRI brain volumes, in cognitively intact elders. METHOD: Healthy older adults, ages 65-85, participated in a 5-year longitudinal study that included structural MRI and cognitive testing administered at baseline and at 1.5 and 5 years postenrollment. Participants included 22 ε4 noncarriers, 15 ε4 carriers who experienced a decline in cognition over the 5-year interval, and 11 ε4 carriers who remained cognitively stable. RESULTS: No baseline cognitive or volumetric group differences were observed. Compared to noncarriers, declining ε4 carriers had significantly greater rates of atrophy in left (p = .001, Cohen's d = .691) and right (p = .003, d = .622) cortical gray matter, left (p = .003, d = .625) and right (p = .020, d = .492) hippocampi, and greater expansion of the right inferior lateral ventricle (p < .001, d = .751) over 5 years. CONCLUSIONS: This study illustrates the variability in phenotypic expression of the ε4 allele related to neurodegeneration. Specifically, only those individuals who exhibited longitudinal declines in cognitive function experienced concomitant changes in brain volume. Future research is needed to better understand the biological and lifestyle factors that may influence the expression of the ε4 allele. (PsycINFO Database Record

Intra- and inter-rater agreement of the Genital Injury Severity Scale.

INTRODUCTION: The Genital Injury Severity Scale (GISS) is a clinimetrically-tested tool in use for quantifying and qualifying external genital injury after sexual intercourse. PURPOSE: To evaluate inter- and intra-rater agreement of the GISS amongst examiner/raters in an urban, ethnically diverse, emergency department based sexual assault center. METHODS: The study was conducted in three phases. Six examiners with various years of experience rated their own cases and each others' cases greater than one year after the initial exam. They rated the photographs and documentation of each case at least one year apart. Another six raters utilized a combination of the photos and documentation simultaneously from the same cases. The evaluation method was the completion of the GISS for each phase. RESULTS: Based on the experience level of the rater, the differences in overall agreement were not significant. Strength of agreement was highest with the combination of photos and documentation with W ranging from 0.60501 (substantial) to 0.91056 (almost perfect). The GISS variables with the highest level of agreement were tissue break type and toluidine blue uptake type, both with photo evaluation alone and combination of documentation and photos (W = 0.72051 and 0.74599, respectively). CONCLUSION: The Genital Injury Severity Scale is a reliable tool to quantify and qualify the severity of external genital injury when used to evaluate a combination of photos and documentation utilizing midlevel providers trained as sexual assault forensic examiners with various years of experience.

Five-Year Longitudinal Brain Volume Change in Healthy Elders at Genetic Risk for Alzheimer's Disease.

Neuropathological changes associated with Alzheimer's disease (AD) precede symptom onset by more than a decade. Possession of an apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for late onset AD. Cross-sectional studies of cognitively intact elders have noted smaller hippocampal/medial temporal volumes in ɛ4 carriers (ɛ4+) compared to ɛ4 non-carriers (ɛ4-). Few studies, however, have examined long-term, longitudinal, anatomical brain changes comparing healthy ɛ4+ and ɛ4- individuals. The current five-year study examined global and regional volumes of cortical and subcortical grey and white matter and ventricular size in 42 ɛ4+ and 30 ɛ4- individuals. Cognitively intact participants, ages 65-85 at study entry, underwent repeat anatomical MRI scans on three occasions: baseline, 1.5, and 4.75 years. Results indicated no between-group volumetric differences at baseline. Over the follow-up interval, the ɛ4+ group experienced a greater rate of volume loss in total grey matter, bilateral hippocampi, right hippocampal subfields, bilateral lingual gyri, bilateral parahippocampal gyri, and right lateral orbitofrontal cortex compared to the ɛ4- group. Greater loss in grey matter volumes in ɛ4+ participants were accompanied by greater increases in lateral, third, and fourth ventricular volumes. Rate of change in white matter volumes did not differentiate the groups. The current results indicate that longitudinal measurements of brain atrophy can serve as a sensitive biomarker for identifying neuropathological changes in persons at genetic risk for AD and potentially, for assessing the efficacy of treatments designed to slow or prevent disease progression during the preclinical stage of AD.

Derivation of the Genital Injury Severity Scale (GISS): a concise instrument for description and measurement of external female genital injury after sexual intercourse.

INTRODUCTION: Inconsistencies abound in the current forensic literature regarding the definition, and as a result, the significance of female genital injury after sexual intercourse. These definitions are based on variables related to the anatomic locations that are examined, the actual physical findings types, and the methods used to detect the findings. PURPOSE: To derive and perform initial clinimetric analyses on a simple instrument that defines, and based on severity, quantifies external genital injury after sexual intercourse. The scale utilizes standard injury definitions and a standardized examination method. METHODS: After empirical investigation, it was determined that the application of the tool would require the use of magnification and toluidine blue in order to have the sensitivity to detect the majority of injuries that occur after sexual intercourse. Separate matrices were constructed based on anatomic locations and injury types from data collected from sexual assault genital injury examination forms. Principal Components Analyses were applied. A clinical model was constructed from the resultant variables, utilizing operational definitions and forming a template for the instrument. RESULTS: A twelve-factor instrument measuring five variables along five "types" of severity and two "classes" of severity ensued. The resultant instrument was tested for internal consistency and differential validity. Very good internal consistency was attained (Cronbach's Coefficient α = 0.8). In a pilot study, the scale was able to distinguish a cohort of sexual assault patients from one of consensual intercourse subjects based on type and class of injury (p < 0.0001). CONCLUSION: The findings presented demonstrate that while employing a standardized examination method, the Genital Injury Severity Scale has utility in defining and measuring external genital injury after sexual intercourse.

A pilot study to test the differential validity of a genital injury severity scale, in development for use in forensic sexual assault examinations.

Methods of examining the sexual assault patient are not standardized and a definition of what constitutes significant genital injury after sexual assault (SA) remains controversial. This pilot study tests the empirical validity (initial differential validity) of a genital injury severity scale (GISS) under development by the authors with the hypothesis that women who report SA have more severe external genital injuries than those who engage in consensual intercourse (CI). In this observational, prospective study, an initially developed GISS is applied and the exam results of 59 CI volunteers and 185 SA patients are compared. All examinations were performed by experienced sexual assault forensic examiners (SAFE) using toluidine blue (TB) and colposcopy. The Independent Samples Median Test indicates a significant difference in median genital injury type between CI and SA subjects (p < 0.0001). There is a significant difference in the prevalence of Class A (less severe) and Class B injuries (more severe) between the SA and the CI groups (SA: Class A 60%/Class B 40%; CI: Class A 90%/Class B 10% (p= 0.0001)). This initial validation study shows effectiveness in using magnification and TB, combined with a standardized injury severity scale, in describing external genital injury in women after sexual intercourse.

Mycoplasma disease and acute chest syndrome in sickle cell disease.

BACKGROUND: Acute chest syndrome (ACS) is the leading cause of hospitalization, morbidity, and mortality in patients with sickle cell disease. Radiographic and clinical findings in ACS resemble pneumonia; however, etiologies other than infectious pathogens have been implicated, including pulmonary fat embolism (PFE) and infarction of segments of the pulmonary vasculature. The National Acute Chest Syndrome Study Group was designed to identify the etiologic agents and clinical outcomes associated with this syndrome. METHODS: Data were analyzed from the prospective study of 671 episodes of ACS in 538 patients with sickle cell anemia. ACS was defined as a new pulmonary infiltrate involving at least 1 complete segment of the lung, excluding atelectasis. In addition, the patients had to have chest pain, fever >38.5C, tachypnea, wheezing, or cough. Samples of blood and deep sputum were analyzed for evidence of bacteria, viruses, and PFE. Mycoplasma pneumoniae infection was determined by analysis of paired serologies. Detailed information on patient characteristics, presenting signs and symptoms, treatment, and clinical outcome were collected. RESULTS: Fifty-one (9%) of 598 episodes of ACS had serologic evidence of M pneumoniae infection. Twelve percent of the 112 episodes of ACS occurring in patients younger than 5 years were associated with M pneumoniae infection. At the time of diagnosis, 98% of all patients with M pneumoniae infection had fever, 78% had a cough, and 51% were tachypneic. More than 50% developed multilobar infiltrates and effusions, 82% were transfused, and 6% required assisted ventilation. The average hospital stay was 10 days. Evidence of PFE with M pneumoniae infection was seen in 5 (20%) of 25 patients with adequate deep respiratory samples for the PFE assay. M pneumoniae and Chlamydia pneumoniae was found in 16% of patients with diagnostic studies for C pneumoniae. Mycoplasma hominis was cultured in 10 (2%) of 555 episodes of ACS and occurred more frequently in older patients, but the presenting symptoms and clinical course was similar to those with M pneumoniae. CONCLUSIONS: M pneumoniae is commonly associated with the ACS in patients with sickle cell anemia and occurs in very young children. M hominis should be considered in the differential diagnosis of ACS. Aggressive treatment with broad-spectrum antibiotics, including 1 from the macrolide class, is recommended for all patients as well as bronchodilator therapy, early transfusion, and respiratory support when clinically indicated.

Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease.

UNLABELLED: PURPOSE Few studies address the association of Chlamydia pneumoniae infection with pulmonary disease and outcome in patients with underlying pathology such as sickle cell disease (SCD). SCD patients are susceptible to the pulmonary disorder known as acute chest syndrome (ACS), where the etiology remains ill defined. The purpose of this study was to analyze the clinical course and outcome of C. pneumoniae-associated ACS among SCD patients as part of the National Acute Chest Syndrome Study. PATIENTS AND METHODS: This was a longitudinal study of SCD patients presenting with ACS to multiple U.S. medical centers. Two hundred ninety-six SCD patients who developed ACS were tested by PCR for C. pneumoniae and by standard techniques for other respiratory pathogens. These infections were evaluated for association with ACS, clinical course, and complications. RESULTS: Forty-one (14%) patients with first episodes of ACS were PCR positive for C. pneumoniae. Compared with other infections, C. pneumoniae-infected patients were older, were more likely to present with chest pain, and had higher hemoglobin levels at diagnosis. Both groups had similar rates of respiratory failure and prolonged hospitalization. Of the 89 patients with single-pathogen infections, 27 (30%) were due to C. pneumoniae, 21% to Mycoplasma pneumoniae, 10% to RSV, 4% to Staphylococcus aureus, and 3% to Streptococcus pneumoniae. CONCLUSIONS: C. pneumoniae was the most prevalent pathogen in this study of ACS and was responsible for significant morbidity. Additional research is required to develop effective treatment guidelines for ACS.