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1.  Robust norms for selected neuropsychological tests in older adults 
The current study provided longitudinal robust norms for individuals age 70 years and older for several neuropsychological tests. We compared baseline neuropsychological test performance in three groups free of dementia at baseline: a robust normative sample free of dementia for at least two post-follow-up assessments, an incident dementia sample which developed new onset dementia during the follow-up and a Lost to Follow-up (LTF) sample. ANCOVAs showed that the robust sample performed better on all neuropsychological tests compared to the incident dementia and LTF samples. These findings support the argument that individuals in transition to developing dementia may reduce the mean, increase the variability and therefore underestimate cognitive performance in normal aging. We suggest that longitudinal robust norms may help mitigate the limitations inherent in cross-sectional normative samples.
PMCID: PMC2610426  PMID: 18572380
Aging; Norms; Dementia; Attrition
2.  Robust norms for selected neuropsychological tests in older adults 
The current study provided longitudinal robust norms for individuals age 70 years and older for several neuropsychological tests. We compared baseline neuropsychological test performance in three groups free of dementia at baseline: a robust normative sample free of dementia for at least two post-follow-up assessments, an incident dementia sample which developed new onset dementia during the follow-up and a lost to follow-up (LTF) sample. ANCOVAs showed that the robust sample performed better on all neuropsychological tests compared to the incident dementia and LTF samples. These findings support the argument that individuals in transition to developing dementia may reduce the mean, increase the variability and therefore underestimate cognitive performance in normal aging. We suggest that longitudinal robust norms may help mitigate the limitations inherent in cross-sectional normative samples.
PMCID: PMC2610426  PMID: 18572380
Aging; Norms; Dementia; Attrition
3.  Robust and Conventional Neuropsychological Norms: Diagnosis and Prediction of Age-Related Cognitive Decline 
Neuropsychology  2008;22(4):469-484.
The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n = 223), MCI (n = 136), and Alzheimer’s disease (AD, n = 162) participants; 84 healthy participants declined to MCI or AD (NL→DEC), and 44 MCI declined to AD (MCI→AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL→DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI→AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions.
PMCID: PMC2661242  PMID: 18590359
cognition; longitudinal; normative data; decline from normal; mild cognitive impairment
4.  Conventional And Robust Quantitative Gait Norms In Community Dwelling Older Adults 
While gait is widely used to assess health status in older adults, normative data is lacking. Our objective was to develop and compare norms for widely used gait parameters in adults age 70 and older using cross-sectional (conventional) and longitudinal (robust) approaches accounting for important confounders such as disease effects on gait.
Cohort study
General community
Community-dwelling older adults (age>70, N=824) without dementia or disability
Eight quantitative gait parameters measured using an instrumented walkway.
Of the 824 subjects (conventional normal; CN sample), 304 were included in a ‘robust normal’ (RN) sample after excluding those with either prevalent or incident clinical gait abnormalities developing within one year of the baseline assessment to account for disease effects on gait performance. Descriptively, the RN sample showed better performance on all selected gait variables compared to the CN sample. For instance, mean gait velocity (± standard deviation) was 105.9±17.9 cm/sec in the RN sample compared to 93.3±23.2 cm/sec in the overall CN sample. Applying a one standard deviation below the mean (70.1 cm/sec) derived from CN sample to define slow gait, 15.9% (131) in overall cohort were classified as abnormal whereas the RN cut-off (88.0 cm/sec) classified 39.7% (327) in the overall cohort as abnormal.
Our findings suggest that cross-sectional conventional norms may under-estimate gait performance in aging. Longitudinal robust norms provide more accurate estimates of normal gait performance and thus may improve early detection of gait disorders in older adults.
PMCID: PMC2955162  PMID: 20646103
gait; reference values; elderly
5.  Profiles of Cognitive Functioning in a Population-Based Sample of Centenarians Using Factor Mixture Analysis 
Experimental aging research  2013;39(2):125-144.
Background/Study Context
The goal of the study was to identify and characterize latent profiles (clusters) of cognitive functioning in centenarians and the psychometric properties of cognitive measures within them.
Data were collected from cross-sectional, population-based sample of 244 centenarians (aged 98-108, 15.8% men, 20.5% African-American, 38.0% community-dwelling) from 44 counties in Northern Georgia participating in the Georgia Centenarian Study (2001-2009). Measures included the Mini-Mental State Examination (MMSE), Severe Impairment Battery (SIB), Wechsler Adult Intelligence Scale-III, Similarities sub-test (WAIS), Finger Tapping, Behavioral Dyscontrol Scale (BDS), Controlled Oral Word Association Test (COWAT), and Fuld Object Memory Evaluation (FOME). The Global Deterioration Rating Scale (GDRS) was used to independently evaluate criterion-related validity for distinguishing cognitively normal and impaired groups. Relevant covariates included directly assessed functional status for basic and instrumental activities of daily living (DAFS), race, gender, educational attainment, Geriatric Depression Scale Short Form (GDS), and vision and hearing problems.
Results suggest two distinct classes of cognitive performance in this centenarian sample. Approximately one-third of the centenarians show a pattern of markedly lower cognitive performance on most measures. Group membership is independently well-predicted (AUC=.83) by GDRS scores (sensitivity 67.7%, specificity 82.4%). Membership in the lower cognitive performance group was more likely for individuals who were older, African Americans, had more depressive symptoms, lower plasma folate, carriers of the APOE ε4 allele, facility residents, and individuals who died in the two years following interview.
In a population expected to have high prevalence of dementia, latent subtypes can be distinguished via factor mixture analysis that provide normative values for cognitive functioning. The present study allows estimates for normative cognitive performance in this age group.
PMCID: PMC3579538  PMID: 23421635
6.  Normative Data in Women Age 85 and Older: Verbal Fluency, Digit Span, and the CVLT-II Short Form 
The Clinical neuropsychologist  2012;26(1):18-30.
Individuals age 85 years and above (i.e., the oldest old) represent the fastest growing segment of the U.S. population and are at increased risk of developing dementia. This represents an important challenge for the clinical neuropsychologist, as the extant normative data on neuropsychological measures remains relatively limited for this age group. Therefore, the aim of the present study was to characterize the performance effects of age and education in a large, well-characterized sample of women between the ages of 85 and 95 years on the CVLT-II Short Form (Delis et al., 2000), verbal fluency tasks, and the WAIS-III Digit Span Test (Wechsler, 1997). In order to minimize the likelihood that women with an incipient neurodegenerative process were included in the final normative sample, we applied regression-based change scores to identify and exclude women who evidenced a statistically significant decline on a global cognitive screening measure over a 20 year interval. The results of our analysis indicate varying influence of age and education on these measures and we provide tables with descriptive statistics stratified by both age and education. Findings from the present normative study are discussed within the context of “robust” longitudinal normative data.
PMCID: PMC3927723  PMID: 22224509
oldest old; normative data; CVLT
7.  The Framingham Heart Study Clock Drawing Performance: Normative Data from the Offspring Cohort 
Experimental aging research  2013;39(1):80-108.
Background/Study Context
While the Clock Drawing Test (CDT) is a popular tool used to assess cognitive function, limited normative data on CDT performance exists. The objective of the current study was to provide normative data on an expanded version of previous CDT scoring protocols from a large community-based sample of middle to older adults (aged 43 to 91) from the Framingham Heart Study.
The CDT was administered to 1476 Framingham Heart Study Offspring Cohort participants using a scoring protocol that assigned error scores to drawn features. Total error scores were computed, as well as for subscales pertaining to outline, numeral placement, time-setting, center, and “other.”
Higher levels of education were significantly associated with fewer errors for time-setting (Command: p<.001; Copy: p=.003), numerals (Command: p<.001) and “other” (Command: p<.001) subscales. Older age was significantly associated with more errors for time-setting (Command: p<.001; Copy: p=.003), numeral (Command: p<.001) and “other” (Command: p<.001) subscales. Significant differences were also found between education groups on the Command condition for all but the oldest age group (75+).
Results provide normative data on CDT performance within a community-based cohort. Errors appear to be more prevalent in older compared with younger individuals, and may be less prevalent in individuals who completed at least some college compared with those who did not. Future studies are needed to determine whether this expanded scoring system allows detection of preclinical symptoms of future risk for dementia.
PMCID: PMC3612583  PMID: 23316738
Clock Drawing Test; Normal aging; Scoring methods; Neuropsychological tests; Dementia; Cognitive screening
8.  Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease 
Brain  2011;135(1):170-180.
Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = −0.31, P = 0.007), including in non-demented patients (β = −0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal–temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in Parkinson's disease.
PMCID: PMC3316476  PMID: 22108576
Alzheimer's disease; dementia; mild cognitive impairment; Parkinson's disease; neurodegeneration
9.  Age-expanded normative data for the Ruff 2&7 Selective Attention Test: Evaluating cognition in older male 
The Clinical neuropsychologist  2012;26(5):751-768.
The Ruff 2&7 Selective Attention Test’s (RSAT) current scoring data are relatively limited for older adults because persons over the age of 70 years were not included in the normative sample. Prior evidence suggests that changes in attention skills, such as those evaluated by the RSAT, may distinguish normal cognitive aging from pathologic cognitive decline. Thus, normative data for older individuals on this measure increases its utility in diagnosing Mild Cognitive Impairment (MCI) and dementia, and enhance its potential use in clinical and research settings. Data from 415 male volunteers (mean age = 69.5 ± 5.7 years) in the PREADViSE clinical trial were used in the current investigation. Analysis of covariance (ANCOVA) shows statistically significant effects of age, race, and education on RSAT Speed measures. Results indicate that age-expanded norms will provide a more accurate reflection of the typical performance of older individuals on the RSAT.
PMCID: PMC3734957  PMID: 22651854
10.  Metabolic Cost of Daily Activities and Effect of Mobility Impairment in Older Adults 
Journal of the American Geriatrics Society  2011;59(11):10.1111/j.1532-5415.2011.03655.x.
There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments.
Cross-sectional observational study.
University based research clinic
Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes.
Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments.
Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments.
Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults.
PMCID: PMC3874461  PMID: 22091979
Energy expenditure; Aging; Disability; Metabolic Efficiency
11.  Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study 
PLoS Medicine  2012;9(2):e1001170.
A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level.
Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.
Methods and Findings
Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.
An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Currently, more than 35 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. Dementia, the commonest form of which is Alzheimer's disease, mainly affects older people and, because more people than ever are living to a ripe old age, experts estimate that, by 2050, more than 115 million people will have dementia. At present, there is no cure for dementia although drugs can be used to manage some of the symptoms. Risk factors for dementia include physical inactivity, infrequent participation in mentally or socially stimulating activities, and common vascular risk factors such as high blood pressure, diabetes, and smoking. In addition, some studies have reported that mild cognitive impairment (MCI) is associated with an increased risk of dementia. MCI can be seen as an intermediate state between normal cognitive aging (becoming increasingly forgetful) and dementia although many people with MCI never develop dementia, and some types of MCI can be static or self-limiting. Individuals with MCI have cognitive problems that are more severe than those normally seen in people of a similar age but they have no other symptoms of dementia and are able to look after themselves. The best studied form of MCI—amnestic MCI (aMCI)—is characterized by memory problems such as misplacing things and forgetting appointments.
Why Was This Study Done?
Much of the expected increase in dementia will occur in low and middle income countries (LAMICs) because these countries have rapidly aging populations. Given that aMCI is frequently used to define groups of people who may be at risk of developing dementia, it would be useful to know what proportion of community-dwelling older adults in LAMICs have aMCI (the prevalence of aMCI). Such information might help governments plan their future health care and social support needs. In this cross-sectional, population-based study, the researchers estimate the prevalence of aMCI in eight LAMICs using data collected by the 10/66 Dementia Research Group. They also investigate the association of aMCI with sociodemographic factors (for example, age, gender, and education), disability, and neuropsychiatric symptoms such as anxiety, apathy, irritability, and depression. A cross-sectional study collects data on a population at a single time point; the 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LAMICs, particularly people with dementia.
What Did the Researchers Do and Find?
In cross-sectional surveys carried out in six Latin American LAMICS, China, and India, more than 15,000 elderly individuals without dementia completed standardized assessments of their mental and physical health and their cognitive function. Interviews with relatives and carers provided further details about the participant's cognitive decline and about neuropsychiatric symptoms. The researchers developed an algorithm (set of formulae) that used the data collected in these surveys to diagnose aMCI in the study participants. Finally, they used statistical methods to analyze the prevalence, distribution, and impact of aMCI in the eight LAMICs. The researchers report that aMCI was associated with disability, anxiety, apathy, and irritability but not with depression and that the prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Other analyses show that, considered across all eight countries, aMCI was modestly associated with being male (men had a slightly higher prevalence of aMCI than women) and with having fewer assets but was not associated with age or education.
What Do These Findings Mean?
These findings suggest that aMCI, as diagnosed using the algorithm developed by the researchers, is consistently associated with higher disability and with neuropsychiatric symptoms in the LAMICs studied but not with most sociodemographic factors. Because prevalidated and standardized measurements were applied consistently in all the countries and a common algorithm was used to define aMCI, these findings also suggest that the prevalence of aMCI varies markedly among LAMIC populations and is similar to or slightly lower than the prevalence most often reported for European and North American populations. Although longitudinal studies are now needed to investigate the extent to which aMCI can be used as risk marker for further cognitive decline and dementia in these settings, the large absolute numbers of older people with aMCI in LAMICs revealed here potentially has important implications for health care and social service planning in these rapidly aging and populous regions of the world.
Additional Information
Please access these Web sites via the online version of this summary at
Alzheimer's Disease International is the international federation of Alzheimer associations around the world; it provides links to individual associations, information about dementia, and links to three World Alzheimer Reports; information about the 10/66 Dementia Research Group is also available on this web site
The Alzheimer's Society provides information for patients and carers about dementia, including information on MCI and personal stories about living with dementia
The Alzheimer's Association also provides information for patients and carers about dementia and about MCI, and personal stories about dementia
A BBC radio program that includes an interview with a man with MCI is available
MedlinePlus provides links to further resources about MCI and dementia (in English and Spanish)
PMCID: PMC3274506  PMID: 22346736
12.  Age and education effects and norms on a cognitive test battery from a population-based cohort: The Monongahela –Youghiogheny Healthy Aging Team (MYHAT) 
Aging & mental health  2010;14(1):100-107.
Performance on cognitive tests can be affected by age, education, and also selection bias. We examined the distribution of scores on a several cognitive screening tests by age and educational levels in a population-based cohort.
An age-stratified random sample of individuals aged 65+ years was drawn from the electoral rolls of an urban U.S. community. Those obtaining age and education-corrected scores ≥ 21/30 on the Mini-Mental State Examination were designated as cognitively normal or only mildly impaired, and underwent a full assessment including a battery of neuropsychological tests. Participants were also rated on the Clinical Dementia Rating scale. The distribution of neuropsychological test scores within demographic strata, among those receiving a CDR of 0 (no dementia), are reported here as cognitive test norms. After combining individual test scores into cognitive domain composite scores, multiple linear regression models were used to examine associations of cognitive test performance with age, and education.
In this cognitively normal sample of older adults, younger age and higher education were associated with better performance in all cognitive domains. Age and education together explained 22% of the variation of memory, and less of executive function, language, attention, and visuospatial function.
Older age and lesser education are differentially associated with worse neuropsychological test performance in cognitively normal older adults representative of the community at large. The distribution of scores in these participants can serve as population-based norms for these tests, and be especially useful to clinicians and researchers assessing older adults outside specialty clinic settings.
PMCID: PMC2828360  PMID: 20155526
Neuropsychological tests; epidemiology; normative; community
13.  Predictive Validity of Demographically-Adjusted Normative Standards for the HIV Dementia Scale 
The aim of the current study was to develop and validate demographically-adjusted normative standards for the HIV Dementia Scale (HDS). Given the association between demographic variables and the HDS summary score, demographically-adjusted normative standards may enhance the classification accuracy of the HDS. Demographically-adjusted normative standards were derived from a sample of 182 seronegative healthy participants and were subsequently applied to a sample of 135 HIV-1 seropositive individuals with multidisciplinary case conference diagnoses of HIV-1-associated neurocognitive disorders (e.g., HIV-1-associated dementia and Minor-Cognitive/Motor Disorder) in proportions consistent with published epidemiologic reports. In the normative sample, age and education (and their interaction) emerged as the only demographic factors significantly associated with the HDS. In comparison to the traditional HDS cut score (raw score total ≤10), use of the demographically-adjusted normative standards significantly improved the sensitivity (from 17.2% to 70.7%, respectively) and overall classification accuracy (increasing the odds ratio from 3 to approximately 6) of the HDS for identifying participants with HIV-1-associated neurocognitive disorders. The application of demographically-adjusted normative standards on the HDS improves the clinical applicability and accuracy of this cognitive screening measure in the detection of HIV-1-associated neurocognitive disorders.
PMCID: PMC3659773  PMID: 17852582
Human immunodeficiency virus; Screening Tests; Dementia; Neuropsychological Assessment
14.  An exploratory cluster randomised trial of a university halls of residence based social norms intervention in Wales, UK 
BMC Public Health  2012;12:186.
Excessive alcohol consumption amongst university students has received increasing attention. A social norms approach to reducing drinking behaviours has met with some success in the USA. Such an approach is based on the assumption that student's perceptions of the norms of their peers are highly influential, but that these perceptions are often incorrect. Social norms interventions therefore aim to correct these inaccurate perceptions, and in turn, to change behaviours. However, UK studies are scarce and it is increasingly recognised that social norm interventions need to be supported by socio ecological approaches that address the wider determinants of behaviour.
To describe the research design for an exploratory trial examining the acceptability, hypothesised process of change and implementation of a social norm marketing campaign designed to correct misperceptions of normative alcohol use and reduce levels of misuse, implemented alongside a university wide alcohol harm reduction toolkit. It also assesses the feasibility of a potential large scale effectiveness trial by providing key trial design parameters including randomisation, recruitment and retention, contamination, data collection methods, outcome measures and intracluster correlations.
The study adopts an exploratory cluster randomised controlled trial design with halls of residence as the unit of allocation, and a nested mixed methods process evaluation. Four Welsh (UK) universities participated in the study, with residence hall managers consenting to implementation of the trial in 50 university owned campus based halls of residence. Consenting halls were randomised to either a phased multi channel social norm marketing campaign addressing normative discrepancies (n = 25 intervention) or normal practice (n = 25 control). The primary outcome is alcohol consumption (units per week) measured using the Daily Drinking Questionnaire. Secondary outcomes assess frequency of alcohol consumption, higher risk drinking, alcohol related problems and change in perceptions of alcohol-related descriptive and injunctive norms. Data will be collected for all 50 halls at 4 months follow up through a cross-sectional on line and postal survey of approximately 4000 first year students. The process evaluation will explore the acceptability and implementation of the social norms intervention and toolkit and hypothesised process of change including awareness, receptivity and normative changes.
Exploratory trials such as this are essential to inform future definitive trials by providing crucial methodological parameters and guidance on designing and implementing optimum interventions.
Trial registration number
PMCID: PMC3315745  PMID: 22414293
15.  Normative influences on intentions to smoke among Greek adolescents: the moderating role of smoking status 
Tobacco Induced Diseases  2014;12(1):5.
Social norms influence adolescent smoking intentions, but this effect may differentiate depending on current smoking experiences. The presented study assessed the moderation effects of smoking status on the relationship between social norms and smoking intentions among Greek adolescents.
A cross-section survey-based design was used. Overall, 251 Greek secondary school students (M age = 16.1 years, 61.2% females) completed structured and anonymous questionnaires including demographic characteristics (age, gender), subjective and descriptive social norms towards smoking, self-reported tobacco use, and intentions to smoke in the next 12 months.
Linear regression analysis showed that social norms overall predicted 36.4% (Adjusted R2) of the variance in intentions. Perceived prevalence of smoking in same age peers and adults, having more close friends who smoke and perceived social approval of smoking predicted intentions to smoke in one year. Moderated regression analysis showed that the effects of social norms on smoking intentions were significantly moderated by smoking status.
Social norms predict smoking intentions, but this effect is stronger among ever (than never) smoker adolescents. Adolescents with smoking experiences may selectively attend to pro-smoking social cues and this perpetuates into their motivation to keep up the habit. School-based interventions should target normative beliefs and related cognitive processes, especially among adolescents who have already initiated tobacco use.
PMCID: PMC3973024  PMID: 24670201
Adolescents; Social norms; Smoking intentions
16.  Semantic memory activation in individuals at risk for developing Alzheimer disease 
Neurology  2009;73(8):612-620.
To determine whether whole-brain, event-related fMRI can distinguish healthy older adults with known Alzheimer disease (AD) risk factors (family history, APOE ɛ4) from controls using a semantic memory task involving discrimination of famous from unfamiliar names.
Sixty-nine cognitively asymptomatic adults were divided into 3 groups (n = 23 each) based on AD risk: 1) no family history, no ɛ4 allele (control [CON]); 2) family history, no ɛ4 allele (FH); and 3) family history and ɛ4 allele (FH+ɛ4). Separate hemodynamic response functions were extracted for famous and unfamiliar names using deconvolution analysis (correct trials only).
Cognitively intact older adults with AD risk factors (FH and FH+ɛ4) exhibited greater activation in recognizing famous relative to unfamiliar names than a group without risk factors (CON), especially in the bilateral posterior cingulate/precuneus, bilateral temporoparietal junction, and bilateral prefrontal cortex. The increased activation was more apparent in the FH+ɛ4 than in the FH group. Unlike the 2 at-risk groups, the control group demonstrated greater activation for unfamiliar than familiar names, predominately in the supplementary motor area, bilateral precentral, left inferior frontal, right insula, precuneus, and angular gyrus. These results could not be attributed to differences in demographic variables, cerebral atrophy, episodic memory performance, global cognitive functioning, activities of daily living, or depression.
Results demonstrate that a low-effort, high-accuracy semantic memory activation task is sensitive to Alzheimer disease risk factors in a dose-related manner. This increased activation in at-risk individuals may reflect a compensatory brain response to support task performance in otherwise asymptomatic older adults.
= Alzheimer disease;
= Analysis of Functional NeuroImages;
= analysis of variance;
= area under the curve;
= Brodmann area;
= blood oxygen level–dependent;
= control;
= Dementia Rating Scale 2;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= episodic memory;
= family history;
= field of view;
= functional region of interest;
= hemodynamic response function;
= mild cognitive impairment;
= Mayo Older Americans Normative Studies;
= magnetic resonance;
= medial temporal lobe;
= not significant;
= Rey Auditory–Verbal Learning Test;
= semantic memory;
= supplementary motor area;
= spoiled gradient-recalled at steady state;
= echo time;
= repetition time;
= voxel-based morphometry.
PMCID: PMC2731619  PMID: 19704080
Patient characteristics are important in the liver transplant (LTX) population because of proven associations between individual and environmental factors, treatment adherence, and health outcomes in general medical and other transplant (txp) populations.
The objective of this report is to determine generalizability of the sample to other LTX populations and to establish reliability of measures used to assess individual and environmental resources.
This is a cross sectional analysis of baseline data in a longitudinal study of adherence and health outcomes.
Ninety first-time adult LTX recipients at the University of Pittsburgh Medical Center completed assessments of socio-demographic, health history, psychosocial and environmental factors shortly after surgery; adherence and health outcomes are tracked throughout the study.
The UPMC cohort is older, less racially diverse, and contains more living donors than the national sample. Our sample is generally comparable to the UPMC cohort on pre-txp socio-demographic and clinical characteristics.
Comparable reliability/internal consistency on psychological measures is demonstrated between our sample and most published norms. The mean scores on all coping scales in our sample are higher than normative. Our subjects indicated a more negative perception of family environment and perceived relationships with their primary caregiver more positively than the normative group.
The generalizability of our sample to the parent population and reliability of individual and environmental measures reported here will enable us to examine relationships and predictive capability of patient and contextual resources on treatment adherence and health outcomes among liver transplant recipients.
PMCID: PMC2858345  PMID: 20397349
liver; transplant; psycho-social; socio-demographic
18.  Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study 
PLoS Medicine  2014;11(4):e1001633.
Radek Bukowski and colleagues conducted a case control study in 59 US hospitals to determine the relationship between fetal growth and stillbirth, and find that both restrictive and excessive growth could play a role.
Please see later in the article for the Editors' Summary
Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.
Methods and Findings
We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.
Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.
Please see later in the article for the Editors' Summary
Editors' Summary
Pregnancy is usually a happy time, when the parents-to-be anticipate the arrival of a new baby. But, sadly, about 20% of pregnancies end in miscarriage—the early loss of a fetus (developing baby) that is unable to survive independently. Other pregnancies end in stillbirth—fetal death after 20 weeks of pregnancy (in the US; after 24 weeks in the UK). Stillbirths, like miscarriages, are common. In the US, for example, one in every 160 pregnancies ends in stillbirth. How women discover that their unborn baby has died varies. Some women simply know something is wrong and go to hospital to have their fears confirmed. Others find out when a routine check-up detects no fetal heartbeat. Most women give birth naturally after their baby has died, but if the mother's health is at risk, labor may be induced. Common causes of stillbirth include birth defects and infections. Risk factors for stillbirth include being overweight and smoking during pregnancy.
Why Was This Study Done?
Stillbirths are often associated with having a “small for gestational age” (SGA) fetus. Gestation is the period during which a baby develops in its mother's womb. Gestational age is estimated from the date of the woman's last menstrual period and/or from ultrasound scans. An SGA fetus is lighter than expected for its age based on observed distributions (norms) of fetal weights for gestational age. Although stillbirth is clearly associated with impaired fetal growth, the exact relationship between fetal growth and stillbirth remains unclear for two reasons. First, studies investigating this relationship have used gestational age at delivery rather than gestational age at death as an estimate of fetal age, which overestimates the gestational age of stillbirths and leads to errors in estimates of the proportions of SGA and “large for gestational age” (LGA) stillbirths. Second, many characteristics that affect normal fetal growth are also associated with the risk of stillbirth, and this has not been allowed for in previous studies. In this population-based case–control study, the researchers investigate the fetal growth abnormalities associated with stillbirth using a new approach to estimate gestational age and accounting for the effect of characteristics that affect both fetal growth and stillbirth. A population-based case–control study compares the characteristics of patients with a condition in a population with those of unaffected people in the same population.
What Did the Researchers Do and Find?
The researchers investigated all the stillbirths and a sample of live births that occurred over 2.5 years at 59 hospitals in five US regions. They used a formula developed by the Stillbirth Collaborative Research Network to calculate the gestational age at death of the stillbirths. They categorized fetuses as SGA if they had a weight for gestational age within the bottom 10% (below the 10th percentile) of the population and as LGA if they had a weight for gestational age above the 90th percentile at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms of fetal weight for gestational age. Population norms incorporate weights for gestational age from normal pregnancies and from pregnancies complicated by growth abnormalities, whereas the other two norms include weights for gestational age from normal pregnancies only. Having an SGA fetus was associated with a 3- to 4-fold increased risk of stillbirth compared to having a fetus with “appropriate” weight for gestational age based on all three norms. LGA was associated with an increased risk of stillbirth based on the ultrasound and individualized norms but not the population norms. Being more severely SGA or LGA (below the 5th percentile or above the 95th percentile) was associated with an increased risk of stillbirth.
What Do These Findings Mean?
These findings indicate that, when the time of death is accounted for and norms for weight for gestational age only from uncomplicated pregnancies are used, stillbirth is associated with both restricted and excessive fetal growth. Overall, abnormal fetal growth was identified in 25% of stillbirths using population norms and in about 50% of stillbirths using ultrasound or individualized norms. Although the accuracy of these findings is likely to be affected by aspects of the study design, these findings suggest that, contrary to current practices, strategies designed to prevent stillbirth should focus on identifying both severely SGA and severely LGA fetuses and should use norms for the calculation of weight for gestational age based on normal pregnancies only. Such an approach has the potential to identify almost half of the pregnancies likely to result in stillbirth.
Additional Information
Please access these websites via the online version of this summary at
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on stillbirth
Tommy's, a UK nonprofit organization that funds research into stillbirth, premature birth, and miscarriage and provides information for parents-to-be, also provides information on stillbirth (including personal stories)
The UK National Health Service Choices website provides information about stillbirth (including a video about dealing with grief after a stillbirth)
MedlinePlus provides links to other resources about stillbirth (in English and Spanish)
Information about the Stillbirth Collaborative Research Network is available
PMCID: PMC3995658  PMID: 24755550
19.  HIV-associated neurocognitive disorders (HAND) in a South Asian population - contextual application of the 2007 criteria 
BMJ Open  2012;2(1):e000662.
To estimate the prevalence of HIV-associated neurocognitive disorders (HAND) among HIV patients in a multiethnic South Asian population, describe the pattern of neurocognitive impairment in HAND and the factors associated with HAND.
A cross-sectional survey of HIV-positive outpatients and inpatients.
The sole referral centre for HIV/AIDS treatment in Singapore.
Inclusion criteria were HIV positive, age between 21 and 80 years old and at least 3 years of education. Exclusion criteria included concomitant delirium, serious systemic disease or major psychiatric illness. 265 patients did not meet criteria or declined to participate. The final sample size was 132.
Outcome measures
The primary outcome measure was cognitive impairment based on performance on the Montreal Cognitive Assessment, International HIV Dementia Scale and Instrumental Activities of Daily Living. The secondary outcome measure was the classification of impairment based on the 2007 updated research nosology for HAND.
The prevalence of HAND was 22.7% of which 70% (15.9% of total) were asymptomatic neurocognitive impairment, 23.3% (5.3% of total) were mild neurocognitive disorder and 6.7% (1.5% of total) were HIV-associated dementia. Increasing age (OR 1.104, 95% CI 1.054 to 1.155, p<0.001), less education (OR 0.78, 95% CI 0.69 to 0.89, p<0.001) and low baseline CD4 count (OR 0.15, 95% CI 0.03 to 0.74, p=0.019) were associated with HAND. Delayed recall, language and abstract thinking were the domains most commonly affected, but impairment in visuospatial ability (RC 3.013, 95% CI 1.954 to 4.073, p<0.001) and attention (RC 2.205, 95% CI 1.043 to 3.367, p<0.001) were most strongly associated with HAND.
HAND is common among HIV patients in a South Asian sample, most of whom are asymptomatic. Older patients with less education and severe illness at diagnosis are at highest risk of HAND. Delayed recall is most commonly affected, but visuospatial dysfunction is most strongly associated with prevalent HAND.
Article summary
Article focus
What is the prevalence of HIV-associated neurocognitive disorders (HAND) in South Asia?
What are the demographic and clinical characteristics of South Asian individuals with HAND?
Key messages
The estimated prevalence of HAND in South Asia is high.
Older patients with less education and more severe HIV illness at diagnosis are at highest risk for HAND.
Early diagnosis of HIV and access to care and treatment is essential.
Strengths and limitations of this study
The article's strengths are it is the first study on HAND in a representative multiethnic South Asian population and it used a method of detection that is applicable to local clinical practice.
The limitations are the small sample size and non-comparability with other HAND studies due to different methods used in detection of HAND cases.
Another major limitation is the lack of published local normative data on the tools used.
PMCID: PMC3282293  PMID: 22331389
20.  Estimates and influences of reflective opposite-sex norms on alcohol use among a high-risk sample of college students: Exploring Greek-affiliation and gender effects 
Addictive Behaviors  2011;37(5):596-604.
Reflective opposite sex norms are behavior that an individual believes the opposite sex prefers them to do. The current study extends research on this recently introduced construct by examining estimates and influences of reflective norms on drinking in a large high-risk heterosexual sample of male and female college students from two universities. Both gender and Greek-affiliation served as potential statistical moderators of the reflective norms and drinking relationship. All participants (N = 1790; 57% female) answered questions regarding the amount of alcohol they believe members of the opposite sex would like their opposite sex friends, dates, and sexual partners to drink. Participants also answered questions regarding their actual preferences for drinking levels in each of these three relationship categories. Overall, women overestimated how much men prefer their female friends and potential sexual partners to drink, whereas men overestimated how much women prefer their sexual partners to drink. Greek-affiliated males demonstrated higher reflective norms than non-Greek males across all relationship categories, and for dating partners, only Greek-affiliated males misperceived women’s actual preferences. Among women however, there were no differences between reflective norms estimates or the degree of misperception as a function of Greek status. Most importantly, over and above perceived same-sex social norms, higher perceived reflective norms tended to account for greater variance in alcohol consumption for Greeks (vs. non-Greeks) and males (vs. females), particularly within the friend and sexual partner contexts. The findings highlight that potential benefits might arise if existing normative feedback interventions were augmented with reflective normative feedback designed to target the discrepancy between perceived and actual drinking preferences of the opposite sex.
PMCID: PMC3395330  PMID: 22305289
reflective norms; college students; alcohol; fraternity and sorority; social norms; normative feedback
21.  Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey 
BMC Neurology  2009;9:48.
1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location.
Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis.
Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR.
Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.
PMCID: PMC2744905  PMID: 19709405
22.  Normative Misperceptions and Temporal Precedence of Perceived Norms and Drinking* 
Journal of studies on alcohol  2006;67(2):290-299.
Previous research has shown that students overestimate the drinking of their peers, and that perceived norms are strongly associated with drinking behavior. Explanations for these findings have been based largely on cross-sectional data, precluding the ability to evaluate the stability of normative misperceptions or to disentangle the direction of influence between perceived norms and drinking. The present research was designed to evaluate (1) the stability of normative misperceptions and (2) temporal precedence of perceived norms and drinking.
Participants were college students (N = 164; 94 women) who completed assessments of perceived norms and reported behavior for drinking frequency and weekly quantity. Most participants (68%) completed the same measures again two months later.
Results indicated large and stable overestimations of peer drinking for frequency and weekly quantity. Results also showed that for weekly quantity, perceived norms predicted later drinking, but drinking also predicted later perceived norms. Results for frequency revealed perceived norms predicted later drinking, but drinking did not predict later perceived norms.
These findings underscore the importance of longitudinal designs in evaluating normative influences on drinking. The present findings suggest that normative misperceptions are stable, at least over a relatively short time period. Findings support a mutual influence model of the relationship between perceived norms and drinking quantity but are more strongly associated with conformity explanations for the relationship between perceived norms and drinking frequency. Results are discussed in terms of implications for prevention interventions.
PMCID: PMC2443635  PMID: 16562412
23.  Normative Data for Neuropsychological Tests in a Rural Elderly Chinese Cohort 
The Clinical Neuropsychologist  2012;26(4):641-653.
Normative information is important for appropriate interpretation of cognitive test scores as a critical component of dementia diagnosis in the elderly population. A cross-sectional evaluation of 1826 participants aged 65 years and older from four rural counties in China was conducted using six cognitive instruments including tests of global cognitive function (the Community Screening Instrument for Dementia), Memory (Word List Learning and Recall tasks from the Consortium to Establish a Registry for Alzheimer’s Disease, IU Story), Language (Animal Fluency Test), and executive function (IU Token). Multiple regression models adjusting for demographic variables were used to provide standardized residuals z-scores and corresponding percentile ranking for each cognitive test. In all cognitive tests, older age was associated with worse test performance while exposure to education was related to better cognitive test performance. We also detected a significant gender difference with men scoring better than women and a significant gender by education interaction on two tests. The interaction indicates that gender difference in test scores was much smaller in participants with more education than those who had less or no education. These demographically adjusted, regression-based norms can be a useful tool to clinicians involved with differential diagnosis of cognitive and memory disorders in older adults in rural China.
PMCID: PMC3349802  PMID: 22439633
Normative Study; Neuropsychological Test; Age; Gender; Education; Regression- Based Norms
24.  Accelerating Cortical Thinning: Unique to Dementia or Universal in Aging? 
Cerebral Cortex (New York, NY)  2012;24(4):919-934.
Does accelerated cortical atrophy in aging, especially in areas vulnerable to early Alzheimer's disease (AD), unequivocally signify neurodegenerative disease or can it be part of normal aging? We addressed this in 3 ways. First, age trajectories of cortical thickness were delineated cross-sectionally (n = 1100) and longitudinally (n = 207). Second, effects of undetected AD on the age trajectories were simulated by mixing the sample with a sample of patients with very mild to moderate AD. Third, atrophy in AD-vulnerable regions was examined in older adults with very low probability of incipient AD based on 2-year neuropsychological stability, CSF Aβ1-42 levels, and apolipoprotein ɛ4 negativity. Steady decline was seen in most regions, but accelerated cortical thinning in entorhinal cortex was observed across groups. Very low-risk older adults had longitudinal entorhinal atrophy rates similar to other healthy older adults, and this atrophy was predictive of memory change. While steady decline in cortical thickness is the norm in aging, acceleration in AD-prone regions does not uniquely signify neurodegenerative illness but can be part of healthy aging. The relationship between the entorhinal changes and changes in memory performance suggests that non-AD mechanisms in AD-prone areas may still be causative for cognitive reductions.
PMCID: PMC3948495  PMID: 23236213
aging; Alzheimer's disease; atrophy; cortical thickness; magnetic resonance imaging
25.  Validity of US norms for the Bayley Scales of Infant Development-III in Malawian children 
Most psychometric tests originate from Europe and North America and have not been validated in other populations. We assessed the validity of United States (US)-based norms for the Bayley Scales of Infant and Toddler Development-III (BSID-III), a neurodevelopmental tool developed for and commonly used in the US, in Malawian children.
We constructed BSID-III norms for cognitive, fine motor (FM), gross motor (GM), expressive communication (EC) and receptive communication (RC) subtests using 5 173 tests scores in 167 healthy Malawian children. Norms were generated using Generalized Additive Models for location, scale and shape, with age modeled continuously. Standard z-scores were used to classify neurodevelopmental delay. Weighted kappa statistics were used to compare the classification of neurological development using US-based and Malawian norms.
For all subtests, the mean raw scores in Malawian children were higher than the US normative scores at younger ages (approximately <6 months) after which the mean curves crossed and the US normative mean exceeded that of the Malawian sample and the age at which the curves crossed differed by subtest. Weighted kappa statistics for agreement between US and Malawian norms were 0.45 for cognitive, 0.48 for FM, 0.57 for GM, 0.50 for EC, and 0.44 for RC.
We demonstrate that population reference curves for the BSID-III differ depending on the origin of the population. Reliance on US norm-based standardized scores resulted in misclassification of the neurological development of Malawian children, with the greatest potential for bias in the measurement of cognitive and language skills.
PMCID: PMC4019333  PMID: 24423629
Child development; testing norms; cross-cultural testing bias

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