Validation of a French version of an informant-based questionnaire as a screening test for Alzheimer's disease

BACKGROUND: Development of informant-based screening tests for dementia is an emerging field. The reliability and validity of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), an instrument that screens for dementia in general, have been established. We conducted a study to validate a French version of the IQCODE as a screening test for Alzheimer's dementia in the elderly living in the community. METHOD: In the Canadian Study of Health and Aging, subjects were screened in their own homes using the modified Mini-Mental State Exam (3-MS). Those who screened positive, along with a sample of subjects who screened negative, were referred for a complete clinical examination. In Quebec, an informant was asked to complete the French version, IQCODE(F), at that time. Based on the final clinical diagnoses, performances of the IQCODE(F) and Mini-Mental State Examination (MMSE, converted from 3-MS) in screening for Alzheimer's disease were evaluated. RESULTS: Of the 237 subjects, the mean IQCODE (F) score was 3.4 (s.d. = 0.6), on a 5-point scale (1 = improvement in condition over the past 10 years, 5 = marked deterioration, 3 = no change). The mean MMSE score was 23.1 (s.d. = 4.5). The scores on the two scales were correlated (r = -0.44, P < 0.001). The IQCODE(F) scores were unrelated to education (r = -0.07, P > 0.3) in contrast to the MMSE scores (r = 0.28, P < 0.001). With respect to a diagnosis of probable Alzheimer's disease, the IQCODE(F) (cut-off point 3.6) had a sensitivity of 75% and a specificity of 95.6%. The sensitivity and specificity of the MMSE (cut-off point 23) were 70% and 82.3% respectively. CONCLUSION: The findings of the IQCODE(F) are consistent with those of the English version in correlation with the MMSE and apparent freedom from educational bias. The IQCODE is superior to the MMSE as a screening test for probable Alzheimer's disease in the elderly living in the community. It may be a useful addition to the screening tests already available, especially for the less well educated.     

Executive dyscontrol: an important factor affecting the level of care received by older retirees

OBJECTIVES: To examine the relative contributions of Executive Control Function (ECF), general cognition, mood, problem behavior, physical disability, demographic variables, and the number of prescribed medications to the level of care received by older retirees. DESIGN: Multivariate regression and discriminant modeling. SETTING: A single Continuing Care Retirement Community (CCRC) in San Antonio, Texas. PARTICIPANTS: A total of 107 older retirees (mean age = 83.7+/-7.2 years), including 17 community-dwelling, well, older controls and 90 CCRC residents. CCRC subjects represented a convenience sample of consecutive referrals for geropsychiatric assessment. Sixty-one subjects resided at a noninstitutionalized level of care, and 46 were institutionalized. MEASUREMENTS: Tests of ECF (the Executive Interview (EXIT25)), general cognition (the Mini-Mental State Examination (MMSE)), mood (the Geriatric Depression Scale short-form (sGDS)), problem behavior (the Nursing Home Behavior Problem Scale (NHBPS)), physical disability (the Cumulative Illness Rating Scale (CIRS)), age, gender, years of education, and the number of prescribed medications were studied. RESULTS: All variables except gender and education varied significantly across level of care. Four variables made significant independent contributions; EXIT25 score (r2 = .48, P< .001), medication usage (partial r2 = .11, P<.001), sGDS score (partial r2 = .06, P = .001), and problem behavior (partial NHBPS r2 = .04, P<.04). These variables accounted for 69% of the total variance in level of care (R2 = .69; F (df 7,99) = 32.1, P<.001). A discriminant model based on the number of prescribed medications, EXIT25, sGDS, and NHBPS scores classified 83.2% of cases correctly (Wilke's lambda = .50, F(5,101) = 20.1; P<.001). The MMSE enters but fails to contribute significantly, independent of the other variables. Age and CIRS scores fail to enter. CONCLUSIONS: Cognitive (particularly ECF) impairment contributes most to the observed variance in level of care received by older retirees in this CCRC. In contrast, markers of general cognition, depression, and physical illness contributed relatively little additional variance. ECF is not detected well by traditional cognitive measures and must be sought by specific tests. Further study is needed to replicate these findings in other populations.     

Second trimester abortion using prostaglandin E2 suppositories with or without intracervical Laminaria japonica: a randomized study

OBJECTIVE: To study cognitive function in an elderly population with persistent impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Fasting and postload 2-h plasma glucose and insulin levels were determined at baseline in a population-based sample of 1,300 people and repeated an average of 3.5 years later in 980 subjects. At follow-up, cognitive function was evaluated in subjects with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a brief neuropsychological test battery. RESULTS: Subjects with persistent IGT scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke Selective Reminding Test long-term memory scores. Multiple linear regression analysis revealed that age, education, and insulin levels (either fasting or 2-h value) were associated with the MMSE score in subjects with persistent IGT. Other potential risk factors for impaired cognitive function were not significantly associated with the MMSE score. CONCLUSIONS: Our study showed that persistent IGT in the elderly is associated with mildly impaired cognitive function, and hyperinsulinemia may account for this association.     

Severity of cognitive impairment in Alzheimer's disease affects list learning using the California Verbal Learning Test (CVLT)

Impairment in list learning is considered a primary symptom of Alzheimer's disease (AD), yet there are no published reports examining the relationship between list learning and severity of cognitive impairment. We gave nine-item and 16-item versions of the California Verbal Learning Test (CVLT; Delis et al., 1987), a standardized shopping list assessment of memory, to 24 AD patients (mean age = 76.2 +/- 8.1; mean years of education = 13.8 +/- 2.4), who were stratified into four groups based on MMSE scores (mean = 16.0 +/- 5.6). ANOVAs revealed severity effects for total list learning (p < 0.001), the first trial (p < 0.001), the last trial (p < 0.001) and short- and long-delay recall measures. Most of these differences seemed due to floor effects. For example, the modal number of words recalled after a delay was 0 by subjects with MMSE scores below 21. Severity of cognitive impairment was associated with the proportion of intrusions such that the most severely demented subjects gave almost entirely intrusion responses. Surprisingly, list length did not significantly affect any of the free recall measures. Our results suggest that list learning and recall seem to be lost relatively early in AD. Measures of list recall like the CVLT may not be useful in tracking severity of cognitive impairment over time.     

The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used as an efficacy measure in clinical drug trials of Alzheimer's disease (AD). We used data from 1,648 AD participants in two identical 26-week multicenter drug trials to examine the distribution of baseline ADAS-Cog scores in relation to selected demographic and clinical variables, Mini-Mental State Exam (MMSE), Global Deterioration Scale (GDS), and Geriatric Evaluation by Relative's Rating Instrument (GERRI) scores. At baseline, the mean (+/-SD) MMSE score was 18 +/- 4, the ADAS-Cog score was 28 +/- 11, and most subjects were in GDS stage 4 or 5. The ADAS-Cog score was statistically significantly correlated with MMSE (R = -0.76, p < 0.0001) and GERRI (R = 0.40, p < 0.0001) total scores. Correlations among the ADAS-Cog items ranged from 0.19 to 0.59 and all were statistically significant (p < 0.0001). In a multiple regression model, younger age, male gender, older age at onset of dementia, use of concurrent estrogen, and use of concurrent anti-inflammatory agents were statistically significantly associated with superior cognitive performance. We also present data on the distribution of ADAS-Cog scores in relation to subjects' age, level of education, MMSE score, and GDS stage. Because age, MMSE score, and GDS stage (and not the ADAS-Cog) are commonly used to select subjects for AD clinical trials, our data should improve the ability of sponsors to predict ADAS-Cog scores of the subjects in their trials on the basis of the inclusion criteria used. Our data also suggest that age, gender, age at onset of dementia, level of education, and use of estrogen (in women) or anti-inflammatory drugs are related to cognitive abilities in AD. Further studies are needed to assess how and when cognitive differences related to these variables arise.     

Differentiation of adult Leydig cells in the neonatal rat testis is arrested by hypothyroidism

OBJECTIVES: To quantify the rate of cognitive decline on the Mini-Mental State Examination (MMSE) in autopsy-diagnosed Lewy body variant (LBV) of Alzheimer's disease (AD) cases. We hypothesized that LBV patients would have a faster cognitive decline and shorter survival compared with patients with pure AD. BACKGROUND: Prior reports have shown extrapyramidal signs to be associated with a poorer prognosis in AD. It has been suggested that LBV is often characterized by a rapidly progressive course. Few data are available regarding the rate of cognitive decline in autopsy-confirmed LBV dementia cases. METHODS: We searched the databases of the University of California-San Diego Alzheimer's Disease Research Center and the Consortium to Establish a Registry in Alzheimer's Disease (CERAD) for dementia cases with 1) an autopsy diagnosis of definite or probable AD (CERAD criteria) with concomitant Lewy bodies and 2) longitudinal MMSE assessments. This resulted in a series of 40 LBV cases and 148 AD cases without Lewy bodies, with comparable baseline MMSE scores, age, and education. The rate of cognitive decline was calculated as the baseline MMSE -- final MMSE. Methods were devised to reduce floor effects on the MMSE. RESULTS: The average rate of cognitive decline was -5.8 +/- 4.5 points/y in LBV and -4.1 +/- 3.0 points/y in AD (t-test, p < 0.01). The LBV group declined a similar amount on the MMSE (means, -10.0 versus -9.6 points) over a significantly shorter time interval (1.9 versus 2.7 years; p = 0.005) than did AD patients. At baseline, the mean MMSE scores were nearly identical (18.2 in LBV; 17.8 in AD), but on follow-up examinations approximately 1, 2, and 3 years later, there were intergroup mean differences of 1.8 points (two-tailed p = 0.19), 4.2 points (p = 0.04), and 5.6 points (p = 0.03), respectively. The LBV cases had shorter survival time from the onset of cognitive symptoms (7.7 +/- 3.0 years versus 9.3 +/- 3.5 years; p = 0.007) and a shorter mean survival after entry/baseline, which was of marginal significance (3.6 versus 4.1 years; p = 0.11). CONCLUSIONS: This study demonstrates that LBV is characterized by a faster cognitive decline and accelerated mortality compared with AD.     

Cerebral blood flow velocity decreases during cognitive stimulation in Huntington's disease

OBJECTIVE: To examine whether activation of cerebral blood flow velocity during cognitive stimulation, as measured by transcranial Doppler ultrasonography (TCD), is altered in patients with Huntington's Disease (HD). BACKGROUND: Previous research suggests that resting cerebral blood flow in symptomatic and asymptomatic HD patients is reduced from expected premorbid levels. The effects of cognitive activation on this relative hypoperfusion in HD has not been studied extensively. METHODS: We measured TCD flow velocity during rest and cognitive testing with the Porteus Maze Test and the Trails Test in 12 normal control subjects and 10 gene-positive HD patients. Percent change (i.e., flow during testing/resting) of flow velocity in the anterior and middle cerebral arteries were compared between groups. Correlations among percent flow velocity change, a disability rating scale, and cognitive test scores were calculated. RESULTS: In control subjects, anterior cerebral artery flow velocity and middle cerebral artery velocity increased during cognitive testing (p=0.001). HD patients showed a smaller blood flow velocity increase in the anterior cerebral arteries during the Porteus Maze Test (p < 0.001) and the Trails Test, Part B (p < 0.001). In the left anterior cerebral artery, flow velocity fell an average of 4.2% below resting baseline levels during the Porteus Maze Test, and 1.2% below resting levels during the Trails Test. The magnitude of the cerebral blood flow velocity changes in the anterior cerebral artery correlated with a number of cognitive test scores and with a rating scale of functional disability. In addition, logistic regression was able to discriminate the HD patients from the control group based on blood flow velocity changes (p=0.0025). When HD patients were divided into more (i.e., HD with chorea; n=4) and less impaired (i.e., without chorea; n=6) groups, both showed significant decreases in left anterior cerebral artery flow velocity during visual spatial executive cognition testing compared with control subjects. CONCLUSIONS: These results suggest that activation of visual spatial executive functions cause decreased flow velocity in the anterior cerebral artery, but not the middle cerebral artery, in HD patients. These changes are related to test performance and functional capabilities.     

The epidemiology of tuberculosis in New South Wales 1975-1995: the effects of immigration in a low prevalence population

Studies have shown that <20% of the US population has periodontal disease. Studies of radiographs have shown that alveolar bone loss increases with age. Bone loss assessed from intraoral radiographs describing 10,282 teeth from 416 subjects seeking dental care during a 3 month period at the University of Washington were studied. The mean age of the subjects was 47.2 years (SD+/-15.2). The youngest subjects (15-24) had on average 29.6 teeth (SD+/-2.2) and the oldest subjects (75-94) 19.3 teeth (SD+/-6.6). This difference was statistically significant (F=16.57, p<0.001). No association was found between alveolar bone loss (CEJ-ABC), and TMD symptoms. Smoking was significantly associated with both general bone loss (CEJ-ABC) (chi(2)=114.9, p<0.0001), and vertical bone defects (angular) (chi(2)=101.8, p<0.0001). In this study population (15-94 years), alveolar bone loss progressed as defined by the slope (beta=0.29) between age 15-44, but was almost flat from age 50 years (beta=0.04). The data suggested an overall rate of alveolar bone loss of 0.02 mm per year. Stepwise multiple regression analysis showed that smoking was the primary factor in bone loss (t= 7.7, p<0.0001), followed by age (t=7.0, p<0.001) and gender (t=3.0, p<0.01). TMD symptoms could not explain the presence and severity of horizontal or vertical defects. If the CEJ-ABC distance above the mean plus 2x the SD was used as the cutoff value to define abnormal bone levels, 10.9% of the younger (15-45 years), and 10.7% of the older subjects (50-94) had significant alveolar bone loss. 73.9% of the younger and 100% of the older subjects with such extent of alveolar bone loss were smokers.     

Epidemiological dementia index: a screening instrument for Alzheimer's disease and other types of dementia suitable for use in populations with low education level

INTRODUCTION: MMSE and CAMCOG are neuropsychological scales developed for use in everyday clinical practice and epidemiological surveys. MATERIAL AND METHODS: These two instruments were used as part of the assessment during an epidemiological survey in the municipality of Pylaia, Greece. The project was based on the World Health Organization Program for Research on Aging and Age-Associated Dementias (1992). It had two phases. During phase I, nursing students collected demographic data, risk factors, personal and family history data and they applied MMSE, CAMCOG and scales of everyday life functioning. During phase II, 4 physicians examined all subjects that manifested possible cognitive deterioration (MMSE<27), in order to reach a final diagnosis. The final diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. MMSE and CAMCOG were not taken into consideration in the diagnostic process. Three hundred and eighty subjects were initially screened. All were aged over 70 years. After the exclusion of subjects who were illiterate, blind, etc., the results of 277 subjects were finally analyzed. Subjects with 6 years of education or less accounted for 92.42% of the total study sample. Twelve of them (5.33%) suffered from Alzheimer's disease, 7 from vascular dementia (2.52%) and 1 suffered from secondary dementia (0.36%). RESULTS: MMSE exceeded 90% sensitivity at the level 22/23 and specificity at 14/15. The levels for CAMCOG were 56/57 and 43/44, respectively. This low performance of both tests is to a large extent due to the functional illiteracy of elderly individuals in Greece, to possible coexistence of mood disorders or simply to lack of cooperation. The analysis of data led to the development of an Epidemiological Dementia Index (EDI), with a scale ranging from 0 to 7. Nondemented subjects had a mean EDI of 5.12 (SD = 1.67) and demented patients had a mean EDI of 1.6 (SD = 1. 92). At the level 4/5 sensitivity was 93.33. Specificity was 93.56 at the level 2/3.     

Measurement of prethrombotic markers in the assessment of acquired hypercoagulable states

Hypercoagulable states can be detected by measuring activation peptides, enzyme-inhibitor complexes, and fibrin/fibrinogen degradation products, which are markers of hemostatic activation. A series of these prethrombotic markers has been evaluated in the elderly, pregnancy, diabetes and acute myocardial infarction patients (n=30 in each group) as well as in hematologic malignancies (n=42). The parameters assayed were: prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complexes (TAT), fibrinopeptide A (FPA), plasmin-alpha2 antiplasmin complexes (PAP) and D-Dimer. Results were compared with those obtained in a group of 30 healthy subjects. We found a significant increase of F1+2, TAT and FPA in elderly (p<0.05), acute myocardial infarction (AMI) (p<0.01), hematologic malignancies (p<0.01), and pregnancy (p<0.0001), indicating a marked clotting activation. Diabetic patients under strict metabolic control only presented a moderate increase of TAT (p<0.05), suggesting a slight activation. We also observed a highly significant elevation of PAP and D-Dimer in elderly (p<0.001), AMI (p<0.0001), and malignancy (p<0.0001), indicating an activation of the fibrinolytic system. The combination of selected fibrinolytic and coagulation measurements is useful for the detection of a hypercoagulable state in conditions characterized by a risk of thrombosis.     

Cognitive changes in very old persons with dementia: the influence of demographic, psychometric, and biological variables

Longitudinal changes in global cognitive functioning, indexed by the Mini-Mental State Examination (MMSE), in subjects with dementia (Alzheimer's disease and vascular dementia) were examined. The roles of several demographic, psychometric, and biological indices in predicting cognitive deterioration were also examined. The sample consisted of 36 very old (M age at entry = 83.0 years, range = 75-95) adults with dementia from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in MMSE scores over the retest interval; the average decline was estimated as 2.43 (SD = 1.81) points per year. Several factors were associated with cognitive deterioration. Higher initial MMSE scores were associated with greater deterioration, whereas superior forward digit span and Block Design at entry were associated with attenuated decline, once differences in baseline severity were accounted for. By contrast, a variety of other putatively important variables exhibited no relationship to decline, including age, gender, education, onset age, dementia type, backward digit span, as well as a number of biological parameters (e.g., vitamin B12, folic acid). The results suggest that although the magnitude of cognitive deterioration in dementia is highly variable, several indicators may be useful predictors of future changes in cognitive functioning.     

Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia

Neuropsychological changes distinguishing mild Alzheimer's disease (AD) from frontotemporal dementia (FTD) have been described, but empirical verification of differential cognitive characteristics is lacking. Archival neuropsychological data on 15 FTD patients, 16 AD patients, and 16 controls were compared. Controls outperformed both patient groups on measures of verbal and nonverbal memory, executive ability, and constructional skill, with AD patients showing more widespread memory decline. No differences were found between the 3 groups in confrontation naming, recognition memory, or basic attention. Patient groups differed only in nonverbal memory, with FTD patients performing significantly better than AD patients. However, patient groups also differed in pattern of performance across executive and memory domains. Specifically, AD patients exhibited significantly greater impairment on memory than executive tasks, whereas the opposite pattern characterized the FTD group. These findings suggest that examination of relative rankings of scores across cognitive domains, in addition to interpretation of individual neuropsychological scores, may be useful in differential diagnosis of FTD versus AD.     

The Mini-Mental State Examination in general medical practice: clinical utility and acceptance

OBJECTIVE: To examine the psychometric properties, acceptance, and screening efficacy of the Mini-Mental State Examination (MMSE) in an internal medicine practice. MATERIAL AND METHODS: The MMSE was administered more than 4,000 times by 27 internists to 3,513 elderly patients (2,299 women and 1,214 men, 60 to 102 years old) who underwent general medical examinations. The efficacy of the MMSE for screening was measured in a subsample of age- and sex-matched patients with dementia (N = 185) and control subjects (N = 227). MMSE scores were correlated with age and education in the community sample. The attitudes of physicians about the MMSE were assessed with a 12-question survey. Sensitivity, specificity, and predictive values were calculated. RESULTS: Performance on the MMSE among persons older than 59 years was influenced by age and education but not by sex. During an interval of 1 to 4 years, a change of 4 or more points in the total MMSE score is needed to indicate substantial cognitive deterioration. Participating physicians considered the MMSE of little value for routine screening in unselected populations but wanted it available for use as a clinical test. The traditional MMSE cutoff score of 23 or less had a sensitivity of 69% and a specificity of 99%. Use of age- and education-specific cutoff scores improved the sensitivity to 82% with no loss of specificity. With use of typical base rates for dementia in a general medical practice, the positive predictive value was less than 35%. CONCLUSION: The clinical utility of the MMSE and acceptance by physicians may be improved through awareness of the influences of age and education on the MMSE and by its application in settings with a high base rate of dementia. The MMSE is ineffective when used to screen unselected populations; it should be used for persons at risk of cognitive compromise.     

Myocardial infarction in the elderly. Comparison between 2 groups of patients over 75 and under 65 years of age

To define the clinical characteristics, prognosis and treatment of myocardial infarction (MI) in the elderly, we retrospectively compared the files of 101 patients aged > or = 75 years (mean: 82 +/- 4 years) and of 120 others aged < or = 65 years (mean: 55 +/- 4.7 years). The figures corresponding to younger patients are presented in brackets. The elderly group included 60.4% women (5%: p < 0.001), 58.9% hypertensive subjects (38.3%: p = 0.005); 30.4% diabetics (11.7%: p = 0.0013) and 12.6% smokers (66.1%: p < 0.001); 20.8% of the elderly had a history of MI (10%: p = 0.002), 15.8% of arteriopathy of the lower limbs (8.3%: p = 0.001) and 6.9% of cerebrovascular accident (1.7%: p = 0.02). Elderly patients were admitted after an average of 26.6 hours (10.4 hours: p < 0.001). Only 56.4% (79.2%) reported typical MI pain, 22.8% (7.5%) had a painless form, 31.8% (4.2%) an initial left ventricular failure, 21.8% (7.5%) a global cardiac dysfunction and 20.8% (4.2%) a cardiogenic shock (p < 0.001 for all comparisons). 63.4% had an anterior MI (40.8%: p < 0.001), 40.6% a Q-form (29.6%: p = NS) and 22.2% an atrial fibrillation (0.8%: p < 0.001). Serum myoglobin and total CK concentrations were significantly lower in elderly subjects. 20.8% of them received beta-blockers (86.7%), 43.6% aspirin (80%), 14.6% oral anticoagulant (56.7%), but 63.4% were given diuretics (25.2%) and 31.7% digitalis alkaloids and positive inotropic drugs (6.7%) (p < 0.001 for all these comparisons). Heparin, nitrates, calcium channel blockers, ACE inhibitors and antiarrhythmics were prescribed as often regardless of age. Only 10 elderly patients (9.9%) were treated with thrombolytics (77: 65%: p < 0.001); 6 (5.9%) underwent coronary angiography (43: 35.8%: p < 0.001), 2 (2%) angioplasty (11: 9.2%) and one (1%) coronary bypass surgery (12: 10%). 35 elderly patients (34.7%) died while in hospital (5: 4.2%), 22 suddenly, 10 in cardiogenic shock and 3 due to arrhythmias. 38 cases (37.8%) of heart failure (21: 17.5%), 21 (20.8%) recurrences of coronary insufficiency (8: 6.7%) and 11 (10.9%) mechanical complications of MI (4: 3.3%) were also observed (p < 0.001 for all these comparisons). Due to lack of sufficient data, we could not define the status of the surviving patients discharged from hospital. The wider use of thrombolytics, angiography and angioplasty (coronary bypass surgery still having a heavy mortality and morbidity) is probably the best way to improve the prognosis of MI in the elderly.     

1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly

BACKGROUND AND PURPOSE: White matter hyperintensities in MRI of the brain are often seen in normal elderly subjects. Radiologically, these hyperintense regions are similar to those in symptomatic patients with subcortical arteriosclerotic encephalopathy (SAE). Our aim was to discriminate white matter hyperintensities (WMH) on MRI in patients with SAE from similar appearing changes in normal elderly. METHODS: Three groups of elderly patients were studied: symptomatic patients with WMH of SAE (n = 5); asymptomatic subjects with diffuse, confluent WMH (n = 4); and elderly control subjects (n = 5). Proton density images revealed WMH in the occipital lobes. Proton magnetic resonance spectroscopy (1H-MRS) was used to acquire spectra in these hyperintensities. Metabolite concentrations were calculated from peak areas of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho). RESULTS: The NAA/Cre and NAA/Cho ratios were reduced in the SAE group compared with the two asymptomatic groups (P < .05). NAA was decreased and Cho elevated in SAE compared with control subjects (P < .05). The average volumes of WMH in the SAE group (65.5 cm3) and in asymptomatic control subjects (59.4 cm3) were similar, and greater than those of the normal control group (4.0 cm3). CONCLUSIONS: Proton MRS discriminates WMH in SAE patients from those in asymptomatic elderly, suggesting differing causes of the hyperintensities.     

Isolated systolic hypertension and cognitive function in the aged. Experience of the Syst-Eur study

OBJECTIVE: To determinate cognitive status and its correlates in older patients with isolated systolic hypertension. METHODS: Syst-Eur is a double-blind placebo-controlled outcome trial conducted in European patients over 60 years of age with isolated systolic hypertension. Moreover, a side-project--the Vascular Dementia Project--is designed to assess cognitive functions and to follow-up their evolution to determine the influence of antihypertensive therapy on vascular dementia incidence. Cognitive functions were evaluated at entry with the MiniMental State Examination (MMSE) in 2250 patients included in Syst-Eur. Cognitive impairment was defined with a MMSE score < or = 23 and led to further evaluation. Baseline blood pressure (BP) was based on the average of six sitting blood pressure readings at three run-in visits 1 month apart. Statistical analysis used Spearman correlation. RESULTS: The MMSE was analysed in 1374 women and 751 men whose mean age was 70 years (range: 60-100). The median level of education expressed as the age at which they stopped their education at school, was 15 years. Baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg. Before randomisation in the trial, 899 (40%) patients had received antihypertensive therapy and 602 (27%) had experienced cardiovascular complications. The MMSE-scores ranged from 15 to 30 (median = 29). The maximal score of 30 was reached by 609 (30%) subjects. Among the 59 (3%) patients with a MMSE-score of 23 or less, 5 were considered to be demented according to the DSM IIIR criteria. The MMSE-scores decreased with advancing age in men (r = -0.16; p < 0.001) and women alike (r = -0.24; p < 0.001). In both men and women, they were positively correlated with the level of education (r = 0.30 and 0.32, respectively; p < 0.001). They were negatively correlated with systolic blood pressure (r = 0.10; p < 0.001) and slightly positively correlated with diastolic blood pressure (r = 0.05; p = 0.03). Previously treated patients or patients reporting cardiovascular complications at baseline had lower MMSE-scores than their non-treated counterparts or subjects without cardiovascular complications (median = 28 and 29, respectively, p < 0.003). CONCLUSION: In a European cohort of 2225 patients over 60 years of age with isolated systolic hypertension, the level of cognitive functions evaluated with the MMSE decreases with advancing age or lesser educational level. It also decreases with higher systolic blood pressure or lower diastolic blood pressure. The influence of antihypertensive therapy on cognitive status will be prospectively evaluated in Syst-Eur Vascular Dementia Project.     

A normative, community-based study of Mini-Mental State in elderly adults: the effect of age and educational level

We investigated community-based data of the Mini-Mental State Examination (MMSE) scores of elderly residents along with the effects of age and educational level. MMSE was planned for all residents over 65 years of age in a town in northern Japan. The number of elders who took the MMSE was 2,266 (90%). The score significantly declined with age and lower educational level, although no effect of sex was apparent. For the MMSE subitems, all the values except for that of naming showed effects of both age and educational level. Those screened by MMSE who fell in the range of cognitive impairment (< 24) accounted for 21.8% and those with severe cognitive impairment (< 18) constituted 6.0%. Despite the differences in language and culture, the mean scores are remarkably similar between Japan and other countries. This is the first normative, community-based study of MMSE among elderly adults in Japan.     

Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test

BACKGROUND: Although an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin-like growth factor-I (IGF-I) may also be of value. OBJECTIVE: To validate the use of serum IGF-I concentration in the diagnosis of GHD in adults. DESIGN: A cross-sectional study. PATIENTS: One hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT. MEASUREMENTS: Serum IGF-I was determined by radioimmunoassay after acid-ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments. RESULTS: According to age- and sex-adjusted population-based references values, 51 patients had serum IGF-I concentrations below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty-seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF-I concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P < 0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P < 0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = -0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001). CONCLUSION: The measurement of serum IGF-I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF-I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.     

Hippocampal sclerosis contributes to dementia in the elderly

OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented elderly, but the anatomic substrate and cognitive profiles of this dementia have not been well established. DESIGN/METHODS: An autopsy series, including dot-immunobinding assay to estimate neocortical synaptic density, of eight patients (three men, five women) with HS on whom extensive antemortem neuropsychological testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to 89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/-12.5) at presentation. Cardiovascular disease was present in 88%, with a mean Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty-three percent had depression or depressive symptoms. Neuropsychologically, most patients presented with prominent memory and language deficits and became progressively demented. Neuropathologically, isolated HS was a rare finding; many patients had either very mild or neocortical "plaque only or plaque predominant" Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical synaptophysin counts were significantly reduced in all HS patients compared with controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic substrate of dementia. Clinically, it can be associated with a course that is difficult to distinguish from AD although cardiac disease and depression are frequent concomitants. Deterioration of cognitive function in these subjects may relate to other pathologic features such as neocortical synapse loss.