Distinguishing objective from subjective assessments of the severity of medication-related safety events among people with Parkinson's disease: a qualitative study.

WHAT IS KNOWN AND OBJECTIVE: Safety events indicating medication-related errors in Parkinson's disease (PD) are common but seldom studied, particularly from lay perspectives. Our objective was to study the meaning and significance to people living with PD of their experience of safety events. METHODS: Twenty qualitative interviews were conducted by telephone with purposively sampled individuals with PD, a proxy, or both, throughout New Zealand. Themes identified from the data included joint assessments of the objective and subjective severity of the individual safety events. RESULTS AND DISCUSSION: Most of the events indicated minor objective errors, whose severity was sometimes perceived as major, especially in the face of callous communication. WHAT IS NEW AND CONCLUSION: Variation between objective and subjective assessments of the severity of possible errors indicated by safety events highlight the importance of distinguishing between, and using, both forms of assessment.

Genetic variations in soluble epoxide hydrolase and graft function in kidney transplantation.

BACKGROUND: Epoxyeicosatrienoic acids (EETs) are endothelium-derived hyperpolarizing factors that contribute renal protective actions. The aim of this study was to identify the association between genetic variations in soluble epoxide hydrolase (EPHX2, EET-metabolizing enzyme) and kidney allograft dysfunction. MATERIALS AND METHODS: Data from 204 kidney transplant donor-recipient pairs were examined for polymorphisms of exon 8 (R287Q, rs751141 G/A) and 3' untranslated region (3' UTR, rs1042032 A/G) of the EPHX2 gene and correlated with clinical data. RESULTS: The mean duration of follow-up for recipients was 58 +/- 45.3 months who were 39 +/- 11.8 years old at the time of operation and displayed estimated glomerular filtration rate (eGFR) of 68 +/- 16.5 mL/min/1.73 m2 at 1 month after transplantation. AA, AG, and GG genotype frequencies in 3' UTR were 28%, 55%, and 16%, respectively. Twenty-one recipients experienced allograft dysfunction with eGFR <30 mL/min/1.73 m2; 10 had AA genotype of rs1042032 polymorphism (chi-square test; A/A vs A/G+G/G; P = .04). Recipients without rs1042032 polymorphism variant allele showed a significant risk for allograft dysfunction (A/A vs A/G+G/G; P = .04; odds ratio, 2.65; 95% confidence interval [CI], 1.03-6.81). Multivariate analysis of the characteristics of patients using a Cox proportional hazard model showed that the AA genotype of rs1042032 polymorphism was predictive of allograft dysfunction (Hazard Ratio = 3.26; P = .04; 95% CI, 1.08-9.59). CONCLUSION: The present study suggested that the presence of the rs1042032 variant allele in EPHX2 was associated with a protective role for allograft function.

In vivo activation of chicken macrophages by infectious bursal disease virus.

Infectious bursal disease virus (IBDV) infects and replicates in the dividing B lymphocytes of chickens. In the present study, the in vivo effect of IBDV infection on chicken macrophage populations and macrophage activation were examined. Specific-pathogen-free chickens were exposed to virulent IBDV and splenic macrophages were recovered during the acute phase of the disease. At 3 and 5 days post-infection (dpi), spleens of virus-exposed chickens had fewer macrophages than those of virus-free controls (p < 0.05). Confocal microscopic examination revealed cells that were positive for both KUL01 (macrophage surface marker) and R63 (IBDVVP2), indicating presence of the virus in macrophages. MQ-NCSU cells, an avian macrophage cell line, were susceptible to replication of IBDV. In addition, splenic macrophages were activated and had temporarily increased levels of mRNA transcripts of pro-inflammatory mediators, including IL-1beta, IL-6, IL-18, and iNOS. The robust expression of proinflammatory cytokine transcripts, along with a decrease in macrophage numbers, suggest that IBDV activates and may lead to a reduction of resident macrophages in vivo.

Alterations in H-ras1 promoter conformation during N-nitroso-N-methylurea-induced mammary carcinogenesis and pregnancy.

We previously demonstrated that H-ras1 oncogene mutations detected in N-nitroso-N-methylurea (NMU)-induced mammary tumors arose as background mutations within rat mammary cells (RMCs) and that NMU promoted the outgrowth of these preexisting mutants. We have now detected a putative DNA structure in the H-ras1 promoter of RMCs in vivo that was absent in NMU-induced mammary tumor cells. Analysis of the promoter in RMCs as a function of time after exposure to carcinogens indicated that NMU, but not 7,12-dimethylbenz(a)anthracene, initiated the loss of this structure with a half-life of 7 days. Although loss of the structure was irreversible in cells that gave rise to tumors, it was restored in normal RMCs by 120 days after exposure and was present in normal RMCs of animals bearing tumors, even 1 year after NMU exposure. The structure was also abrogated in RMCs during pregnancy and restored after lactation was terminated, suggesting that reversible regulation of the structure by hormones contributed to normal RMC growth. Thus, NMU may promote abnormal RMC growth by mimicking the effects of hormones on DNA conformation. We hypothesize that the NMU-induced alterations in promoter conformation irreversibly deregulates H-ras1 expression in initiated cells, thereby increasing the phenotypic penetrance of the conditional H-ras1 mutations.

Enzymatic amplification and characterization of large DNA fragments from genomic DNA.

Conditions for DNA amplification in vitro using modified T7 DNA polymerase have been devised to obtain 2000-bp DNA fragments of the HGPRT gene directly from human genomic DNA. The DNA obtained from a 1.2 x 10(5)-fold amplification has been used for direct sequencing.

Hippocampal atrophy correlates with clinical features of Alzheimer disease in African Americans.

CONTEXT: Imaging measurements may aid in the characterization and diagnosis of patients with Alzheimer disease (AD). Most research studies, however, have been performed on predominantly white study groups despite the fact that there may be biological differences in AD between African American and white patients. OBJECTIVE: To measure hippocampal volume in African American patients with AD and to correlate these measurements with the presence of AD and neuropsychological test performance. DESIGN: Survey study. SETTING: Academic center. PARTICIPANTS: Fifty-four healthy African American subjects and 32 African American patients with AD were studied. Hippocampal volumes were measured in all subjects from magnetic resonance images using established methods. MAIN OUTCOME MEASURE: Correlations were assessed between hippocampal volume and demographic variables, clinical group membership, and neuropsychological performance. RESULTS: The hippocampi of patients were atrophic with respect to those of healthy subjects (P<.01). Significant direct correlations were present between hippocampal volumes and performance on several different neuropsychological tests (r>0.5 and P<.01 for every test evaluated) when patients and healthy subjects were combined. CONCLUSIONS: Hippocampal atrophy is a feature of AD in African Americans as it is in white subjects. The neuropsychological-hippocampal volume correlations indicate that hippocampal volume measurements do represent a measure of the structural substrate of functional impairment in AD.

Levodopa therapy and survival in idiopathic Parkinson's disease: Olmsted County project.

We studied survival in all Olmsted County Parkinson's disease (PD) patients seen at the Mayo Clinic from 1964 to 1978, attempting to answer two questions: (1) What effect does levodopa have on survival in PD? and (2) Does the timing of levodopa administration influence survival? We chose this period because it allowed us to study patient records with a spectrum of disease durations before levodopa treatment; in many patients, the treatment delay was exclusively due to levodopa being unavailable prior to 1969. Mortality of the entire PD cohort (N = 179; 61% levodopa-treated) was greater than that of the general population (matched chronologically, geographically, and by age and gender). Lower age at onset of motor symptoms, lower Hoehn and Yahr stage at first neurologic visit for parkinsonism, and treatment with levodopa were all independent predictors of improved survival. Using a time-dependent Cox regression model, we assessed the impact of the timing of levodopa administration during the course of illness on mortality, while statistically controlling for other factors (ie, patient selection for levodopa treatment, and independent predictors of survival). Risk of death following initiation of levodopa was significantly reduced (p < 0.001), regardless of pre-levodopa duration of illness. This reduction gradually diminished over a period of 4 years on levodopa, but continued to be significantly reduced. After 4 years, increasing survival benefit again progressively accrued over time to at least 17 years of levodopa treatment (p < 0.001). At no point in time was levodopa treatment associated with increased mortality, arguing against substantial levodopa toxicity. However, despite levodopa-improved survival, mortality continues to be increased in PD relative to the general population.

Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.

OBJECTIVES: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. METHODS: An unselected series of 67 individuals participating in the Mayo Alzheimer's Disease Research Center/Alzheimer's Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. RESULTS: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle--only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p < 0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41). CONCLUSIONS: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.

Syncope in the elderly.

This report describes the evaluation of syncope in 210 elderly patients as compared with 190 younger patients. The elderly group had a mean age of 71 years (range 60 to 90) and the younger group had a mean age of 39 years (range 15 to 59). A cardiovascular cause was found in 33.8 percent of the elderly and in 16.8 percent of the young (p = 0.0001), a noncardiovascular cause in 26.7 percent of the elderly and 37.9 percent of the young (p = 0.02), and unknown cause in 38.5 percent of the elderly and 45.3 percent of the young (NS). Prolonged electrocardiographic monitoring established the diagnosis in 17 percent of the elderly but in only 8 percent of the young (p = 0.008). Syncope resulted in trauma in 39 percent of the elderly and in 32 percent of the young, but the elderly more often had major trauma. The two-year overall mortality was 26.9 +/- 3.4 percent in the elderly and 8.3 +/- 2.1 percent in the young (p less than 0.0001). The overall mortality and incidence of sudden death in the elderly with a cardiovascular diagnosis were similar to those in the young; however, in the elderly with a noncardiovascular diagnosis and syncope of unknown cause, the mortality and incidence of sudden death were higher. Multivariate analyses using mortality and sudden death as endpoints revealed that a cardiovascular cause of syncope was a very strong risk factor. In patients with a noncardiovascular cause or unknown cause of syncope, a history of congestive heart failure, older age, and male sex are important prognostic factors.

Prolonged electrocardiographic monitoring in patients with syncope. Importance of frequent or repetitive ventricular ectopy.

The purposes of this study were to document the findings on prolonged electrocardiographic monitoring in patients with syncope, correlate these findings with symptoms during monitoring, and define the prognostic importance of these findings. A total of 235 patients with syncope in whom a cause was not assigned or suggested by the initial history, physical examination, and electrocardiography were studied. Although a variety of arrhythmias were documented during monitoring, the vast majority of arrhythmias were of short duration and did not produce symptoms. At two years, the patients with frequent or paired premature ventricular contractions (PVCs) when compared with patients with rare PVCs, had a higher incidence of sudden death (18.2 percent versus 4.0 percent; p less than 0.001) and higher overall mortality (28.3 percent versus 10.8 percent; p less than 0.003). Similarly, patients with ventricular tachycardia, when compared with patients with rare PVCs, had a higher incidence of sudden death (18.7 percent versus 4.0 percent; p less than 0.0001) and higher overall mortality (36.5 percent versus 10.8 percent; p less than 0.00001). Cox regression analyses revealed that frequent or repetitive PVCs and sinus pauses were independent electrocardiographic predictors of sudden death and mortality in patients presenting with syncope. Therefore, patients with syncope and frequent or repetitive ventricular ectopy or sinus pauses constitute a high-risk subgroup and may be candidates for more extensive diagnostic evaluation.

Variability in anticoagulation control predicts thromboembolism after mechanical cardiac valve replacement: a 23-year population-based study.

OBJECTIVE: To assess optimal control of blood anticoagulation to maximize antithrombotic protection after mechanical cardiac valve replacement. DESIGN: A population-based study of 96 patients with a mean follow-up of 7.7 years (range, 1 month to 23 years) was performed in Olmsted County, Minnesota, and 10,301 prothrombin time (PT) ratios were determined after mechanical heart valve replacement. MATERIAL AND METHODS: PT ratios were analyzed in a new time-dependent Cox proportional-hazards model by defining an algorithm for comparing variability in PT ratios at each month of follow-up and relating these to thromboembolic events. The new method was compared with several conventional time-independent definitions. RESULTS: During 740 person-years of follow-up, 19 of 96 patients (20%) had 27 thromboembolic events. Of these 19 patients, 8 (42%) had events within 3 months after valve replacement. Freedom from any thromboembolic event was 72% at 15 years. The event rate was high (7.5% per year) during high variability and low (0.9% per year) during low variability in the PT ratio. This relationship was lost when time dependence was removed. More PT ratios were less than 1.5 during high (27%) than during low (19%) variability. Several conventional definitions of adequacy of anticoagulation that averaged PT ratios before a thromboembolic event or throughout follow-up or that compared the proportion of PT ratios above or below a fixed ratio did not define or only partially defined different thromboembolic risks. CONCLUSION: Periods of high and low variability of PT ratios define high and low risk of thromboembolism, respectively.

Protein-losing enteropathy after the Fontan operation.

Patients were observed after the Fontan operation to determine the frequency and severity of protein-losing enteropathy. A total of 427 patients who survived for 30 days after the Fontan operation, performed between 1973 and January 1987, were analyzed and, thus far, protein-losing enteropathy has developed in 47 of 427. The cumulative risk for the development of protein-losing enteropathy by 10 years was 13.4% among 30-day survivors, and 5-year survival after the diagnosis was 46%. Hemodynamic studies done coincident with the diagnosis of protein-losing enteropathy have shown increased systemic venous pressure, decreased cardiac index, increased pulmonary vascular resistance, and increased ventricular end-diastolic pressure. Medical management of protein-losing enteropathy was only partially successful. Statistical analysis has shown that factors related to protein-losing enteropathy were ventricular anatomy, increased preoperative ventricular end-diastolic pressure, longer operative bypass time, increased length of hospital stay, and postoperative renal failure. This study suggests that scrupulous selection of cases for the Fontan operation is mandatory and that certain perioperative factors may predispose to this serious complication of the Fontan procedure.

The small aortic root and the Medtronic Hall valve: ultrafast computed tomography assessment of left ventricular mass following aortic valve replacement.

BACKGROUND AND AIMS OF THE STUDY: The selection of an appropriate size aortic valve substitute with respect to patient size and life-style, in the presence of a small aortic root, is problematic, and a decision to enlarge the aortic annulus is often arbitrary. An aortic valve substitute-patient mismatch may place an excessive load on the left ventricle resulting in residual left ventricular mass with attendant patient morbidity and mortality. The aim of this study was to assess the adequacy of the Medtronic Hall valve in the small aortic root using ultrafast computed tomography analysis of left ventricular mass. MATERIALS AND METHODS: In 13 patients the smallest Medtronic Hall valves (size 20 and 21; measured internal orifice area of 2.01 cm2 for both) were used to replace the native aortic valve. All patients had aortic stenosis, and left ventricular hypertrophy was established by echocardiography. The mean body surface area was 1.8 +/- 0.2 m2 (range 1.50-2.06 m2) and the mean weight was 75 +/- 15 Kg (range 50-97 Kg). The mean preoperative New York Heart Association functional class was 3.54 +/- 0.5. RESULTS: There was no operative or late mortality. At a mean follow up of 22 months after aortic valve replacement, the mean left ventricular mass index was 89 +/- 11.4 g/m2 (normal left ventricular mass index by ultrafast computed tomography = 97 +/- 14 g/m2) and mean New York Heart Association functional class was 1.6 +/- 0.8 (p (Binomial) = 0.0001 compared to preoperative). Doppler echocardiogram demonstrated a mean gradient across the prosthetic valve of 17 +/- 7 mmHg. There was no trend towards greater left ventricular mass index in patients with greater body surface area or weight. In no patient was the aortic annulus enlarged. CONCLUSIONS: Trends from this preliminary data suggest that implanting the smallest Medtronic-Hall aortic valves (sizes 20 and 21) results in normal left ventricular mass following aortic valve replacement in patients up to a body surface area of 2.06 m2 and provides support for the notion that an aortic annulus enlarging procedure was not necessary in this group of patients.

Normothermic retrograde cardioplegia is effective in patients with left ventricular hypertrophy. A prospective and randomized study.

Twenty patients with left ventricular hypertrophy (LVH) undergoing isolated aortic valve replacement were prospectively randomized to receive either continuous retrograde normothermic (n = 8) or intermittent retrograde hypothermic (n = 12) methods of myocardial protection. Biopsies of the left ventricular septum were evaluated for ultrastructure and assayed for ATP. There was no mortality, no requirement for intra-aortic balloon pump nor neurological events in any of the patients from either group. Myocardial ATP (warm 23.2 +/- 1.8 nmol/mg protein; cold 22.4 +/- 1.2 nmol/mg protein; p = 0.72) and myocardial CPK-MB (warm 43.6 +/- 5.2 U/l; cold 39.0 +/- 2.5 U/l; p = 0.67) were not significantly different. Ultrastructure was generally well preserved in the biopsies from both groups, with the exception of one patient in the normothermic group. Systemic lactate sampled after 40 minutes of cardiopulmonary bypass was significantly higher in the normothermic group (warm 3.4 +/- 0.27 mmol/l; cold 2.3 +/- 0.21 mmol/l; p = 0.01), however, the myocardial lactate production was not significantly different between the two groups (extraction ratio; warm 0.01 +/- 0.3; cold 0.13 +/- 0.1; p = 0.45). We conclude that the continuous normothermic retrograde method of myocardial protection is effective in patients with left ventricular hypertrophy; however, the higher systemic lactate levels using this technique raises concerns regarding the adequacy of systemic perfusion at 37 degrees C.

[Serum beta 2-microglobulin and carcinoembryonic antigen in patients with bronchogenic carcinoma].

In patients with bronchogenic carcinoma of various types and stages, serum beta 2-microglobulin (beta 2-M) and carcinoembryonic antigen (CEA) were assayed simultaneously. The concentrations of serum beta 2-M and CEA were found to be statistically related to complete remission of the tumor (P less than 0.01). But it was also found that there was no correlation between the levels of beta 2-M and CEA (r = 0.0621). In follow-up, the CEA was found to be increasing incessantly as the disease progressed. For the level of serum beta 2-M, as the patients' condition got worse, it first rose, then dropped and became markedly lower before the patient died. The serum beta 2-M was often elevated 3-5 months earlier than CEA, and frequently resumed the normal level later than CEA after the carcinoma had a complete remission. With the progression of the bronchogenic carcinoma, elevation of beta 2-M was not necessarily a sign of poor prognosis. In contrast, with the serum beta 2-M markedly lowered after an initial elevation, the serum CEA became elevated, the prognosis was usually poor. The authors believe that, in patients with lung cancer, CEA produced from the lung cancer cells would give a level fluctuating with the size of the primary focus and the extent of the metastasis. But its positive rate is rather low. The serum beta 2-M is produced indirectly by certain immunologic function against bronchogenic carcinoma or its metabolites and not by the cancer cells directly. The positive rate of beta 2-M is high, so slightly is its false positive rate.(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-surgical treatment of small cell lung cancer with chemo-radio-immunotherapy and traditional Chinese medicine].

54 consecutive cases of small cell lung cancer (SCLC) were treated with longterm short-interval combined treatment modalities of chemotherapy, radiotherapy (55-65 GY), immunotherapy, traditional Chinese medicine (leaf of Asiatic Ginseng, root of Astragalus membranaceus Bge, etc) and other adjuvants. Chemotherapy consisted of vincristine, cyclophosphamide, methotrexate and carmustine. A complete response of 59.2%, partial response of 38.9% and an overall response of 98.1% were achieved. According to Kaplan-Meier, the survival rates of SCLC with limited disease for 1, 3, 5 and 10 years were 78.1%, 42.6%, 32.1% and 21.4% respectively; while those with extensive disease for 1, 3, and 5 years 90.5%, 13.4% and 13.4%. According to classification of international TNM staging (1988), the survival rates of stage II SCLC for 1, 3, 5 and 10 years were 92.9%, 61.9%, 53.1% and 31.8% respectively; of stage IIIa for 1, 3 and 5 years 80.0%, 30.0% and 20.0%, and of stage IIIb 83.3%, 20.8% and 15.6%. Our combined modalities raised the survival rates considerably; the improved effect was mainly due to the long-term (especially more than 2 years or 10 courses), short-interval, effective and timely combined treatment with chemotherapy, radiotherapy and adjuvants such as traditional Chinese medicine and immunotherapy. By using the above therapeutic strategy, 10 out of 12 SCLC patients including 4 with extensive disease, who were relatives of our hospital staffs, have gained more than 3-17 years of survival. Therefore small cell lung cancer even with extensive disease was a hopeful curable disease.

[Combined modality treatment of small cell lung cancer by chemotherapy, radiotherapy, immunotherapy and Chinese traditional medicine].

The combined modality treatment consisted mainly of long-term intermittent combination chemotherapy (VCMB being in the majority) and radiotherapy combined with immunotherapy as well as Chinese traditional medicine. The patients treated with this therapy were observed in 1974-1986, till successive fifty, and followed up to January 1988. They were of the stage I, II, III and IV including 3, 10, 20 and 17 patients respectively. The complete remission rate was 54% (27/50); the partial remission rate, 40% (20/50). The total effective rate was 94% (47/50). According to the calculation of life-table, 2-year survival rate for the stage I-II (n = 13) was 76.2%; 5-year survival rate, 55.5%. For the stage III (n = 20), 2-year survival rate was 46.9%; 5-year, 18.8%. By long-term combined modality, the survival rate has obviously improved, and the possibility of cure has evidently increased.

Review article: transesophageal echocardiography.

Since 1990, we have performed transesophageal echocardiography (TEE) on 508 patients. This procedure has provided valuable information. The author reviews the indications and usage of TEE in various clinical settings and the need for further evaluation.

Doppler echocardiography in normal functioning valve prostheses.

Even though there has been some criticism regarding the Doppler evaluation in prosthetic valves because of inter-observer and intra-observer variability, among other factors, and Doppler study has a tendency to have falsely high gradients compared to invasive studies, especially mechanical aortic prostheses, Doppler evaluation can provide reliable hemodynamic information about valve function. This test may be particularly useful if used serially, when baseline values are known. Doppler measurement of gradient and valve area has an expected normal range that is specific for the prosthetic type, size, anatomical position, and chronological age. Clearly, a database involving these aspects is needed to provide a more accurate normal range. This study is intended to provide guidance for echocardiographers.

The incidence of MCI differs by subtype and is higher in men: the Mayo Clinic Study of Aging.

OBJECTIVE: Although incidence rates for mild cognitive impairment (MCI) have been reported, few studies were specifically designed to measure the incidence of MCI and its subtypes using published criteria. We estimated the incidence of amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in men and women separately. METHODS: A population-based prospective cohort of Olmsted County, MN, residents ages 70-89 years on October 1, 2004, underwent baseline and 15-month interval evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychological testing. A panel of examiners blinded to previous diagnoses reviewed data at each serial evaluation to assess cognitive status according to published criteria. RESULTS: Among 1,450 subjects who were cognitively normal at baseline, 296 developed MCI. The age- and sex-standardized incidence rate of MCI was 63.6 (per 1,000 person-years) overall, and was higher in men (72.4) than women (57.3) and for aMCI (37.7) than naMCI (14.7). The incidence rate of aMCI was higher for men (43.9) than women (33.3), and for subjects with ≤12 years of education (42.6) than higher education (32.5). The risk of naMCI was also higher for men (20.0) than women (10.9) and for subjects with ≤12 years of education (20.3) than higher education (10.2). CONCLUSIONS: The incidence rates for MCI are substantial. Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women.