Role of active and environmental tobacco smoke on susceptibility to osteoporosis in women undergoing dual-X-ray absorptiometry.

PURPOSE: Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA). METHODS: On 01/06/2018, general practitioners from "COMEGEN" Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters'. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI). RESULTS: Among 10,616 subjects, 3942 were currently smokers [CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m2], 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m2) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m2). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m2) received the Op diagnosis. PS showed an increased Op risk compared to NS [odds ratio (OR) 1.38 (1.14-1.67)] and comparable to CS [OR 1.02 (0.84-1.24)]. CONCLUSION: The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.

Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis.

PURPOSE: We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. METHODS: Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to "COMEGEN" general practitioners' cooperative operating in Naples, Southern Italy. RESULTS: Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. CONCLUSION: In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Metabolic syndrome is associated to an increased risk of low bone mineral density in free-living women with suspected osteoporosis.

PURPOSE: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. METHODS: 13,182 free-living Caucasian women referring to "COMEGEN" general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. RESULTS: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08-1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. CONCLUSIONS: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Circulating leptin is associated with serum uric acid level and its tubular reabsorption in a sample of adult middle-aged men.

PURPOSE: Leptin is associated with cardiovascular risk factors (e.g. hypertension, insulin resistance, kidney disease and excess body weight). Experimental studies showed that leptin might affect serum uric acid, by modulation of the uric acid excretion. However, there are few observational data on the relationship between leptin and uric acid in the general population. Therefore, the aim of the present study was to evaluate the relationship between leptin and uric acid and its excretion in a large middle-aged male general population. METHODS: A sample of 930 adult male individuals (mean age: 52 years) without therapy for high uric acid was included in the analysis (the Olivetti Heart Study). RESULTS: Uric acid was significantly and positively associated with blood pressure, BMI, waist circumference, insulin resistance, C-reactive protein and leptin (p < 0.01), while inversely with renal function (p = 0.01). The multivariate analysis confirmed the association between leptin and uric acid after adjustment for potential confounders (p < 0.01). After division for adiposity, this trend was confirmed separately for normal weight and excess body weight participants. Moreover, leptin was inversely associated with excretion of uric acid (p < 0.01), also in multivariate analysis (p = 0.03). CONCLUSION: The results of this study indicate a positive association between circulating leptin levels and uric acid, independently of potential confounders, both in normal and excess body weight men. Furthermore, an inverse association between leptin and uric acid excretion was detected.

Validation of an easy questionnaire on the assessment of salt habit: the MINISAL-SIIA Study Program.

BACKGROUND/OBJECTIVES: The aim of the present study was to validate a short questionnaire on habitual dietary salt intake, to quickly and easily identify individuals whose salt consumption exceeds recommended levels. SUBJECTS/METHODS: A total of 1131 hypertensive subjects participating in the MINISAL-SIIA study were included in the analysis. Anthropometric indexes, blood pressure, and 24-h urinary sodium excretion (NaU) were measured. A fixed-sequence questionnaire on dietary salt intake was administered. RESULTS: NaU was significantly associated with scores, with a linear association across categories (p for trend <0.0001). In addition, participants who achieved a total score above the median value (eight points) had significantly higher NaU than those whose score was below median (p < 0.0001). In the total sample, the prevalence of "high NaU" (NaU > 85 mmol/day) and "very high NaU" (NaU > 170 mmol/day) was 86 and 35%, respectively. The score of the questionnaire had a significant ability to detect both "high NaU"-with a specificity of 95% at the score of 10 points-and "very high NaU"-with a specificity of 99.6% at score of 13 points. CONCLUSIONS: The main results of the study indicates that a higher score of this short questionnaire is distinctive of habitual high salt consumption in hypertensive patients.

Leptin levels predict the development of insulin resistance in a sample of adult men-The Olivetti Heart Study.

BACKGROUND AND AIMS: Leptin (LPT) is associated with unfavourable cardio-metabolic risk profile. Although a number of studies have found a positive association between LPT and insulin resistance (IR), no observational study has evaluated a prospective association to detect a predictive role of LPT in IR. Therefore, the aim of this study was to estimate the role of LPT on the incidence of IR in an 8-year follow-up of a sample of adult men (The Olivetti Heart Study). METHODS AND RESULTS: The study included 527 not diabetic men without IR (homeostasis model assessment - HOMA index < 2.77 UI) at baseline. Baseline LPT was significantly and positively associated with HOMA index, body mass index (BMI), waist circumference and blood pressure. At the end of the 8-year follow-up period, a positive and significant association was detected between baseline LPT and changes in HOMA index (r = 0.25, p < 0.01) and incidence of IR (OR: 2.6, 95%CI: 1.9-3.4). This trend was also confirmed after adjustment for potential confounders. In addition, the predictive value of LPT was found in subjects who had not experienced any weight increase over the years, and for normal weight and excess body weight participants, separately. CONCLUSIONS: The results of this prospective study suggest a predictive role of circulating LPT levels on a reduction of insulin sensitivity over time, independently of main potential confounders, in non-diabetic men without IR at baseline. In addition, in normal weight individuals, LPT levels were associated with development of IR.

Diet and primary prevention of stroke: Systematic review and dietary recommendations by the ad hoc Working Group of the Italian Society of Human Nutrition.

BACKGROUND AND AIMS: To systematically review the latest evidence on established and emerging nutrition-related risk factors for incidence of and mortality from total, ischemic and haemorrhagic strokes. The present review was conducted in the framework of the work carried out through 2015 and 2016 for the preparation of the Italian Guidelines for the Prevention and Treatment of Stroke, 8th Edition, by ISO-SPREAD (Italian Stroke Organization and the Stroke Prevention and Educational Awareness Diffusion). METHODS AND RESULTS: Systematic review of articles focused on primary prevention of stroke published between January 2013 to May 2016 through an extensive search of the literature using MEDLINE/PUBMED, EMBASE and the Cochrane Library. Articles were ranked according to the SIGN methodology while the GRADE system was used to establish the strength of recommendations. As a result of our literature search, we examined 87 meta-analyses overall (mainly of prospective studies), a few isolated more recent prospective studies not included in the meta-analyses, and a smaller number of available randomized controlled trials and case-control studies. Based on the analysis of the above articles, 36 Syntheses of the available evidence and 36 Recommendations were eventually prepared. The present document was developed by organizing the available evidence into three individual areas (nutrients, food groups and dietary patterns) to provide a systematic and user-friendly overview of the available evidence on the relationship between nutrition and primary prevention of stroke. Yet analysis of foods and food patterns allowed translating the information about nutrients in a tool more amenable to use in daily life also in the light of the argument that people eat foods rather than nutrients. CONCLUSIONS: The present literature review and dietary recommendations provide healthcare professionals and all interested readers with a useful overview for the reduction of the risk of total, ischemic and haemorrhagic stroke through dietary modifications.

The Olivetti Heart Study: Predictive value of a new adiposity index on risk of hypertension, blood pressure, and subclinical organ damage.

BACKGROUND AND AIMS: Recently, some studies have indicated that a new anthropometric index, body adiposity index (BAI), could be more strongly correlated with the percentage of body fat than BMI. However, the results on its role in predicting cardiovascular risk were not univocal. Therefore, the aim of our study was to compare the predictive role of BMI and BAI on risk of hypertension (HP), blood pressure (BP) changes, and subclinical organ damage after an 8-year follow-up, in a sample of adult men participating in the Olivetti Heart Study. METHODS AND RESULTS: Participants were 350 untreated normotensive men without diabetes, examined twice at baseline (1994-95) and after 8 years of follow-up [2002-04]. BMI was expressed as kg/m(2). BAI was calculated according to the following formula: [(hip circumference (cm)/height(1.5) (m)) - 18]. Subclinical organ damage was detected by urinary albumin excretion (UAE) and left ventricular mass, evaluated by the Cornell product (CP). At baseline, BAI and BMI were both associated with diastolic blood pressure (DBP) and mean arterial pressure (MAP). After 8 years, both baseline BAI and BMI were associated with changes (Δ) in systolic BP, MAP and pulse pressure, while only BMI was also positively related to ΔDBP. Analysis of HP incidence showed that both indices were significant predictors of HP. In addition, both BAI and BMI were significantly associated with ΔUAE, but not with ΔCP. Analysis of the changes in BAI and BMI confirmed these results, as the two indices were significantly associated with risk of HP and changes in BP and UAE, but not with changes in CP. CONCLUSIONS: In this sample of healthy adult men, BAI and BMI were significant predictors of risk of HP and changes in BP, after an 8-years follow-up. In addition both indices predicted UAE changes, but neither was associated with the CP changes.

Potassium-rich diet and risk of stroke: updated meta-analysis.

Recently a few prospective population studies provided additional and heterogeneous information concerning the reported statistical associations between potassium (K) intake and stroke risk. Therefore, we updated our previous meta-analysis of K intake and risk of cerebrovascular events. Three studies were added to the previous analysis, and the results of the comparison between the event rate in the two extreme categories of K intake were used. Pooled analysis of 14 cohorts (overall 333,250 participants and 10,659 events) showed an inverse and significant association between K intake and risk of stroke (Relative Risk: 0.80; 95% CI: 0.72-0.90). Our results indicated a favorable effect of higher K intake on risk of stroke. These results confirm the appropriateness of worldwide recommendations for a population increased consumption of potassium-rich foods to prevent cardiovascular disease.

Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men.

BACKGROUND AND AIM: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity. METHODS AND RESULTS: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables. CONCLUSIONS: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.

High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study.

BACKGROUND: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. PATIENTS AND METHODS: The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6). RESULTS: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI. CONCLUSIONS: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.

A higher prevalence of hypertension has been associated with the G-->A/GT (Gly40Ser) polymorphism of the glucagon receptor gene (GCGR) in two population studies. As the mutated receptor is less responsive to glucagon, it has been speculated that the increased susceptibility to hypertension is due to deprivation of the recognized natriuretic effect of the hormone. To test this hypothesis we determined the frequency of the polymorphic variant and evaluated the segmental renal sodium handling by the clearances of uric acid and of exogenous lithium in the Olivetti Heart Study participants (n=971). The polymorphic variant was present only in heterozygous form in 37 individuals (3.8%). After controlling for age and body mass index, the carriers of the variant were twice more likely to be hypertensive and almost three times more likely to be on antihypertensive treatment at the time of examination. Compared to participants carrying the wild type, those carrying the Gly40Ser allele had higher serum uric acid and lower fractional excretion of uric acid and exogenous lithium, independently of age, body mass, and current pharmacological treatment. We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.

Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure: interaction with age. Cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study.

METHODS: The association of the Trp64Arg polymorphism of the beta3-adrenoceptor (beta3-AR) gene with high blood pressure, central adiposity and other features of the metabolic syndrome was investigated in a large unselected sample of a white male working population in Southern Italy (n = 979). RESULTS: In the whole population, subjects heterozygous for the Trp64Arg mutation (11.2%) were not different from the homozygous Trp64Trp for any of the variables investigated. However, upon stratification for age, among men in the upper tertile of age (> 53 years), the Trp64Arg genotype was associated with higher waist: hip ratio (0.992 +/- 0.021 versus 0.982 +/- 0.037, P< 0.05), serum uric acid (6.34 +/- 1.50 versus 5.75 +/- 1.30 micromol/l, P < 0.05) and systolic blood pressure (144.3 +/- 19.4 versus 136.9 +/- 18.9 mmHg, P< 0.05) compared with the wild-type homozygotes. Accordingly, in the same age group, the carriers of Trp64Arg genotype were more often in the upper tertile of abdominal adiposity (69.7 versus 43.7%, P< 0.02) and serum uric acid (56.3 versus 34.8%, P < 0.02) and were more often hypertensive (68.6 versus 57.6%, P< 0.058) than the Trp64Trp homozygotes. No such differences were observed in younger age groups. No association was found with fasting serum insulin and the homeostasis model assessment (HOMA) index of insulin resistance. Furthermore, in a subgroup of 457 men for whom retrospective 20-year follow-up data were available, the variant genotype was associated with a higher probability of developing overweight (44.7 versus 27.0%, P < 0.05) and a trend to higher blood pressure (52.6 versus 38.4%, P = 0.09) over 20 years. CONCLUSION: We conclude that the Trp64Arg variant of the beta3-AR receptor predicts a greater tendency to develop abdominal adiposity and high blood pressure with advancing age.

Slowed information processing in HIV-1 disease. The Multicenter AIDS Cohort Study (MACS).

This investigation examined the effects of HIV-1 infection on speeded complex cognitive processing in a group of HIV-negative (n = 666), HIV-positive symptomatic (n = 156), and HIV-positive asymptomatic (n = 623) participants while controlling for the effects of slowed motor functioning, peripheral neuropathy, and several other putative confounds. Stroop Interference and reaction-time tasks served as anchor procedures to assess cognitive processing. The present findings suggest that HIV-1 infection is capable of compromising CNS-mediated cognitive processes (speeded processing) infringing upon their efficacy in the symptomatic stages of the disease while sparing individuals in the asymptomatic stage. The detrimental effects observed on information-processing mechanisms associated with HIV infection persisted despite the use of procedures to control for peripheral nerve integrity and other potential confounds.

The African-American Health Project (AAHP): study overview and select findings on high risk behaviors and psychiatric disorders in African American men.

The AAHP investigated the neurobehavioral and psychosocial sequelae of HIV-1 and substance use in urban African American men. A community resident sample of 502 African American men stratified by HIV-1 serostatus, drug use and sexual orientation were recruited. A comprehensive battery of measures of neurobehavioral and health status, lifestyle and psychosocial characteristics were administered to all participants, and a stratified sub-sample of 120 participants were tested using state of the art brain imaging techniques to investigate differences in the functional and neurophysiologic effects of HIV-1 and substance use. An overview of the methodology of the AAHP and results on high risk sexual and substance use behaviors, and psychiatric disorders are presented and discussed. The sample was primarily HIV-negative (63%), heterosexual (49% gay or bisexual) and a high percentage used substances during the past year (56% used drugs and 30% moderate/heavy drinkers). High-risk sexual practices were relatively prevalent, and a high percentage reported a history of STDs and other infections. Finally, 25% had a current psychiatric disorder, with gays/bisexuals and HIV-seropositives evidencing greater psychiatric vulnerability. More research is needed to further explore the apparent greater risk for psychiatric disorders among gay and bisexual men, and to determine whether being African American and lower social class exacerbate this risk.

Cognitive functioning in premenstrual syndrome.

OBJECTIVE: To evaluate cognitive functioning in women with premenstrual syndrome (PMS) and controls during the follicular and luteal phases of the menstrual cycle. METHODS: Thirty women with PMS and 31 controls were selected on the basis of psychiatric interview and prospective daily diary recordings. Subjects were tested on two occasions, follicular (days 8-10) and luteal (days 24-26), using complex tasks consisting of measures validated previously for the assessment of "executive" frontal-lobe functions. Tests were counterbalanced for order across subjects. RESULTS: The Beck Depression Inventory scores were significantly different between the groups and across time (P < .001). Women with PMS had a mean luteal phase Beck score of 13.3 consistent with mild-to-moderate premenstrual depression. There were no statistically significant score differences in tests for attention, memory, cognitive flexibility, and overall mental agility. The evaluation of our preliminary data with 30 PMS subjects and 31 controls indicated a very small effect size (.02). To detect an effect size this small (if in fact one exists) with a power of .8 would require a sample of more than 1000 subjects per group. CONCLUSION: Our sample of women with PMS failed to demonstrate objective evidence of diminished cognitive performance, despite subjective feelings of inadequacy.

Normative data stratified by age and education for the Neuropsychological Screening Battery for Hispanics (NeSBHIS): Initial report.

Neuropsychological assessment of monolingual Spanish-speaking people in the United States is both a common practice and an ethical dilemma. Lack of appropriate tests, the absence of norms, use of interpreters, and the multiplicity of in-house translations of commonly used measures add to the problem of accurate assessment. This paper helps address the lack of appropriate measures for the neuropsychological assessment of Latinos in the United States by providing a standardization of the Neuropsychological Screening Battery for Hispanics (NeSBHIS). Normative data on a sample of 300 Hispanic subjects stratified by gender, age, and education are provided. Current results reveal that not one measure of cognitive functioning is free from education effects. Both nonverbal measures and psychomotor speed measures were highly related to education. Age effects were noted on measures of psychomotor speed, visuospatial reasoning, and visuoconstructive skills. Gender effects were found on measures of psychomotor speed and language, with males achieving higher scores than females. The limitations of the current findings are considered. Further research for the validation of the NeSBHIS with clinical populations, as well as further normative data collection at the national and international levels, is needed.

Detection of Alzheimer disease in individuals with Down syndrome.

A comprehensive baseline of emotional functioning was established for adults with Down syndrome. Five emotional factors were studied using groups of (a) adults with Down syndrome (n = 30), (b) clinical control subjects with dementia of the Alzheimer type (n = 18), and (c) elderly control subjects without mental retardation (n = 25). Results of planned statistical comparisons showed indifference, pragnosia, and inappropriateness as primary emotional factors separating Down syndrome and Alzheimer disease groups from elderly control subjects without mental retardation. Indifference was also shown to covary with cognitive mental state, whereby increased levels of indifference were associated with decreased levels of cognitive functioning. The possibility of noncognitive variables signalling dementia of the Alzheimer type in individuals with Down syndrome was discussed.