Normative Data for Neuropsychological Tests in a Rural Elderly Chinese Cohort

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.     

The relationship between neuropsychological test performance, social functioning, and instrumental activities of daily living in a sample of rural older adults

This study examined the relationship between neuropsychological functioning, activities of daily living, and social interaction in a biracial sample of 133 rural community-dwelling participants with fewer than 10 years of education, who were tested twice over 4 years as part of a normative study. Neuropsychological tests predicted self-reported IADL and social functioning at Time 1 after accounting for age, education, health, depression, and gender. Physical health and the Initiation and Perseveration subscale of the Mattis Dementia Rating Scale best predicted instrumental activities of daily living. Social functioning was best predicted by gender and delayed memory recall from the Fuld Object Memory Evaluation. Functional independence and social activities declined slightly over time for all participants, but those whose neuropsychological test scores declined significantly at Time 2 reported less independence and fewer social activities at Time 1 than those participants whose cognition remained stable. Ecological and concurrent validity of self-report measures of functional status and neuropsychological testing in predicting cognitive decline are discussed.     

Cognitive function in relapsing multiple sclerosis: minimal changes in a 10-year clinical trial

BACKGROUND: Although cognitive impairment is common in patients with multiple sclerosis (MS), its value as a clinical trial endpoint remains uncertain. For example, in the randomized, blinded, pivotal trial of glatiramer acetate (GA) in patients with relapsing MS, improvements occurred in neuropsychological test scores during 2 years of treatment regardless of whether patients received GA or placebo, likely due to practice effects. OBJECTIVES: To assess long-term changes in neuropsychological status following 10 years of prospective evaluation in a typical immunotherapy trial cohort. METHODS: Participants in the ongoing open-label GA extension study repeated the Brief Repeatable Battery of Neuropsychological Tests an average of 10.6+/-0.4 years after their initial baseline evaluation. RESULTS: Mean scores on tests of memory and semantic retrieval were not significantly changed over 10 years of follow-up, but tests of attention showed declines for the group as a whole. Using a threshold of a 0.5 SD decline to define significant worsening, individual tests showed declines in 27-49% of participants and a composite score showed worsening in 19%. Controlling for age, gender, and education level, cognitive tests tended to worsen more in participants with better baseline cognitive test scores and higher EDSS scores. Changes in cognitive test scores during the first 2 years of observation were predictive of 10-year changes. CONCLUSIONS: Most patients with relapsing MS had stable cognitive performance during 10 years of prospective evaluation, some of which may be related to a therapeutic effect of GA. Because cognitive changes occur slowly on average, they may not be responsive enough to serve as useful endpoints in studies of course-modifying therapies in relapsing MS.     

A new verbal learning and memory test for English- and Spanish-speaking older people.

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE). moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values.     

Inspection time in non-demented older adults with mild cognitive impairment

The aim of this study was to examine inspection time (IT) performance in older adults with mild cognitive impairment (MCI), who are at higher risk of developing further cognitive decline or dementia. IT is described as an index of speed of informational intake. IT correlates with measures of fluid intelligence and is possibly a marker for the integrity of the cholinergic system of the brain. IT may therefore be useful in aiding the diagnosis of early-stage progressive cognitive impairment. The current study compares IT in 28 people with MCI to 28 age, gender and education-matched controls. The computer-based, visual IT task required participants to discriminate between two visual stimuli that were presented for brief periods. Participants' IT performance was compared to their performance on cognitive and memory tasks. Group comparison showed that participants with MCI performed significantly worse on IT than controls and was not affected by years of education. In combination with other clinical, neuropsychological and biological tests, IT may be a useful assessment tool for improving the identification of older adults at risk for clinically relevant cognitive decline.     

Age and education effects and norms on a cognitive test battery from a population-based cohort: The Monongahela–Youghiogheny Healthy Aging Team

Objectives: Performance on cognitive tests can be affected by age, education, and also selection bias. We examined the distribution of scores on several cognitive screening tests by age and educational levels in a population-based cohort.

Method: An age-stratified random sample of individuals aged 65+ years was drawn from the electoral rolls of an urban US community. Those obtaining age and education-corrected scores ≥21/30 on the Mini-Mental State Examination (MMSE) 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 (CDR) 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.

Results: 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.

Conclusion: Older age and lesser education are differentially associated with worse neuropsychological test performance in cognitively normal older adult representatives of the community at large. The distribution of scores in these participants can serve as population-based norms for these tests, and can be especially useful to clinicians and researchers assessing older adults outside specialty clinic settings.     

Cognitive function in the oldest old: women perform better than men

OBJECTIVE: Limited formal education is associated with poor cognitive function. This could explain sex differences in cognitive function in the oldest old. Whether limited formal education explains differences in cognitive function between elderly women and men was explored. METHODS: The Leiden 85-plus Study is a population based study investigating all 85 year old inhabitants of Leiden with an overall response rate of 87%. A sample of 599 participants were visited at their place of residence. The mini mental state examination was completed by all participants. Cognitive speed and memory were determined with four neuropsychological tests in participants with a mini mental state examination score higher than 18 points. RESULTS: The proportion of women with limited formal education was significantly higher than that of men (70% v 53%, p=0.001), but women had better scores for cognitive speed and memory than men (p<0.05). After adjustment for differences in limited formal education and the presence of depressive symptoms, the odds ratio for women to have a higher cognitive speed than men was 1.7 (95% CI; 1.0 to 2.6), and for them to have a better memory the odds ratio was 1.8 (95%CI; 1.2 to 2.7). CONCLUSION: Women have a better cognitive function than men, despite their lower level of formal education. Limited formal education alone, therefore, cannot explain the differences in cognitive function in women and men. These findings support the alternative hypothesis that biological differences, such as atherosclerosis, between women and men account for the sex differences in cognitive decline.     

The association between depressive mood and cognitive performance in an elderly general population - the MEMO Study

The aim of this study was to analyse the influence of the severity of depressive symptoms on different domains of cognitive function in the elderly. In a population-based cross-sectional study, 385 participants aged 65-83 years were interviewed with the Center for Epidemiologic Studies Depression Scale (CES-D) and performed a standardized neuropsychological test assessing attention, memory, cognitive speed and motor function. Multivariate linear regression analyses revealed a significant effect of depressive symptoms on a single test (Stroop test 1) and two summary scores (memory and motor function). After full adjustment for education and Mini Mental State Examination, the memory score was partly attenuated. Stratified analysis showed that an increase in CES-D scores led to a larger decline of cognitive test results in participants with mild to moderate depressive symptoms, compared to those with a high degree of depressive symptoms. Our results suggest that depressive mood in older adults is primarily associated with decreased processing speed and motor functioning, but not executive control functions. According to our results depressive mood is not necessarily associated with memory deficits in older adults. Changes in depressive symptoms in milder forms of depressive mood are associated with a larger decline in cognitive function than in severer forms of depressive mood.     

Relationship of neuropsychological performance to functional status in nursing home residents and community-dwelling older adults.

OBJECTIVES: The authors examined the association between neuropsychological tests of executive functioning and episodic memory and functional disability in nursing home residents versus community-dwelling older adults. METHODS: The neuropsychological performance of 96 residents from the Jewish Home and Hospital, Bronx, NY and 192 gender- and age-matched older adults from residential communities in the New York metropolitan area was assessed in eight tasks (Word List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency, Trailmaking A and B, and Digit Symbol Substitution). Functional status was derived from the Clinical Dementia Rating scale (CDR) extended activities of daily living scores. Regression analyses were performed to test for differences in cross-sectional age-gradients for cognitive and functional status between nursing home residents and community-dwellers. Furthermore, regression analyses, controlling for age, gender, dementia status, and education, were performed to determine the association between neuropsychological performance and functional status, comparing domains of executive functioning and memory. RESULTS: Community-dwelling older adults showed age-related deficits both in overall cognitive status and functional disability, which were larger in nursing home residents. Executive functioning was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, overall cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning is associated with functional deficits in both community-dwelling older adults and nursing home residents. Measures of executive functioning may prove useful in intervention studies aimed at delaying institutionalization.     

Cognition and beta-amyloid in preclinical Alzheimer's disease: data from the AIBL study

The ‘preclinical’ phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between β-amyloid burden and cognition during this time. We investigated this relationship using a large sample of apparently healthy older adults (N = 177), which also enabled examination of whether the relationship differed according to age, gender, years of education, apolipoprotein E status, and the presence of subjective memory complaints. In addition to episodic memory, a range of cognitive measures (global cognition, semantic memory, visuospatial performance, and executive function) were examined. Participants were aged over 60 years with no objective cognitive impairment and came from the imaging arm of the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study of ageing. ¹¹C-PiB PET was used to measure β-amyloid burden and a PiB ‘cut-off’ level of 1.5 was used to separate participants with low PiB retention from those with high PiB retention. Thirty-three percent of participants had a PiB positive scan. PiB positive participants were 5 years older, twice as likely to carry an apolipoprotein E ?4 allele, and their composite episodic memory was 0.26 SD worse than PiB negative volunteers. Linear regressions with β-amyloid burden as a dichotomous predictor, revealed an interaction between β-amyloid burden and gender, as well as age and education effects, in predicting episodic memory and visuospatial performance. In females, but not in males, increased β-amyloid was related to worse episodic memory and visuospatial performance. Furthermore, an interaction between β-amyloid burden and APOE status was found in predicting visuospatial performance, whereby there was a trend for increased β-amyloid to relate to worse visuospatial performance for those without an APOE ?4 allele. There were no other main or interaction effects of β-amyloid on any of the other composite cognitive measures. These cross-sectional findings suggest that β-amyloid burden does not have a large effect on cognition in this subset of apparently healthy older people. The finding of gender differences deserves further research to answer definitively the important question of gender susceptibility to adverse cognitive effects from β-amyloid.     

The Memory and Aging Telephone Screen: Development and preliminary validation

BackgroundTelephone interviews are widely used in geriatric settings to identify eligible research participants and to perform brief follow-up assessments of cognition. This article reports on the development and validation of the Memory and Aging Telephone Screen (MATS), a structured interview for older adults with mild cognitive impairment and/or significant memory complaints. We also developed three alternate forms of the MATS objective memory test to reduce practice effects engendered by multiple administrations.MethodsParticipants were enrolled in a longitudinal study that included 120 older adults with amnestic mild cognitive impairment, subjective cognitive complaints but without deficit on neuropsychological tests, and demographically matched healthy controls. An additional 15 patients with mild probable Alzheimer’s disease completed the alternative forms study. All participants received the original MATS version, and a subset (n = 90) later received two of three alternate forms.ResultsThe MATS was sensitive to group differences, and the alternate forms were equivalent. MATS objective memory test scores showed adequate stability during a period of 1 year and were moderately correlated with scores on a widely used list-learning test (California Verbal Learning Test, Second Edition).ConclusionsThe MATS, a repeatable telephone screen that includes objective and subjective memory assessments, is useful for detecting individuals in the preclinical and early stages of dementia. Results encourage use of the MATS as a reliable and valid cognitive screening tool in research and clinical settings. Longitudinal assessments are being performed to investigate the predictive validity of the MATS for cognitive progression in mild cognitive impairment.     

The Stick Design test: a new measure of visuoconstructional ability.

Visuoconstructional ability is an important domain for assessment in dementia. Use of graphomotor measures dominate this area; however, participants with low education produce results that cannot be easily interpreted. Our objective was to develop and validate a nongraphomotor assessment of visuoconstructional ability for use in dementia evaluations in persons with low or no education. In a longitudinal, population-based study of dementia among Yoruba residents of Ibadan, Nigeria aged 65 years and older, participants underwent clinical assessment with a battery of cognitive tests and consensus diagnosis. Performance on two visuoconstructional tests, Constructional Praxis and Stick Design, were compared. Gender, age, and education affected performance on both tests. The Stick Design test was more acceptable than Constructional Praxis as measured by the number of participants with total test failure (3.9% vs. 15.1%). The Stick Design test was significantly more sensitive to cognitive impairment and dementia than the Constructional Praxis test. We conclude that Stick Design is a reasonable test of visuoconstructional ability in older cohorts with very limited educational exposure and literacy.     

One-trial 10-item free-recall performance in Taiwanese elderly and near-elderly: A potential screen for cognitive decline

To explore a one-trial 10-item free-recall test as a potential dementia screening tool, we analyzed recall scores and individualized serial position effects in near-elderly (N = 2,336) and elderly (N = 2,371) participants in a population-based survey in Taiwan. Age and sex were significantly associated with recall score [younger > older (p < 0.001); men > women (p < 0.001)]; after controlling for gender and age group, weak association between recall and education was still observed. By contrast, serial position effects (SPEs), defined for each participant and analyzed aggregated over each age group, were not associated with education and tended not to be associated with sex. Primacy effects were observed in 67 to 80 percent, and recency effects were observed in 41 to 54 percent of respondents. Because SPEs were defined for each respondent, we could determine that loss of the primacy effect was associated with significantly larger losses in total recall score in elderly persons who had exhibited both SPEs at the first survey, as compared to those who maintained both SPEs at successive surveys (p < 0.01). Elderly subjects showed slight longitudinal decline in free recall. A one-trial 10-item free-recall test demonstrated age-related cognitive decline in this Taiwanese population survey cohort; SPEs at the individual level may be useful markers for important cognitive change and warrant further study and benchmarking against valid and reliable tests of memory and cognitive decline.     

Neuropsychological deficits in frontotemporal dementia and Alzheimer's disease: a meta-analytic review

We sought to identify the cognitive tests that best discriminate between Alzheimer's disease (AD) and frontotemporal dementia (FTD). A comprehensive search of all studies examining the cognitive performance of persons diagnosed with AD and FTD, published between 1980 and 2006, was conducted. Ninety-four studies were identified, comprising 2936 AD participants and 1748 FTD participants. Weighted Cohen's d effect sizes, percentage overlap statistics, confidence intervals and fail-safe Ns were calculated for each cognitive test that was used by two or more studies. The most discriminating cognitive tests were measures of orientation, memory, language, visuomotor function and general cognitive ability. Although there were large and significant differences between groups on these measures, there was substantial overlap in the scores of the AD and FTD groups. Age, education, years since diagnosis and diagnostic criteria did not significantly contribute to the group differences. Given the large overlap in the test performance of persons diagnosed with AD and FTD, cognitive tests should be used cautiously and in conjunction with a medical history, behavioural observations, imaging and information from relatives when making differential diagnoses.     

Normative data of a brief neuropsychological battery for Spanish individuals older than 49

There is an increasing need for standardized assessment of cognition in older patients that is relatively brief, easy to administer, and has normative data adjusted for age and educational attainment. We tested 332 literate, cognitively normal, Spanish persons older than 49 years from the Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades (Barcelona, Spain) with measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis, and executive functions. Several of the tests were affected by age, education, and/or gender, but the language of administration (i.e., Spanish or Catalan) did not affect the test scores. Standardized scores and percentile ranks were calculated for each age and/or education group for use by clinical neuropsychologists.     

Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study

Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.     

Evidence that response inhibition is a primary deficit in ADHD

The present study examined response inhibition in children with attention deficit hyperactivity disorder (ADHD; n = 58) and controls (n = 84) using three go/no-go tests -- one with high working memory demand (cognitive), one with low working memory demand (simple), and one with rewards and response costs (motivation linked) in which emphasis was on reward for responding to "go" stimuli. Results of a repeated measure analysis of variance showed a significant effect of diagnosis for errors of commission for the simple, cognitive, and motivation-linked go/no-go tests, such that children with ADHD made significantly more errors than controls. Furthermore, a significant effect of test was noted across groups, such that both children in the ADHD and control groups performed worse on the cognitive and motivation-linked tests than they did on the simple test. The diagnosis by test interaction was not significant, suggesting that ADHD participants showed a similar degree of impairment to that of controls, regardless of the degree of working memory load or feedback provided in the test. In children with ADHD, response inhibition appears to be a primary deficit that is observed even when executive function demands of tasks are minimal. Although increasing working memory demand appears to impede response inhibition, this effect is similar in ADHD and typically developing children.     

Computerized Cognitive Training Enhances Episodic Memory by Down-Modulating Posterior Cingulate-Precuneus Connectivity in Older Persons With Mild Cognitive Impairment: A Randomized Controlled Trial

ObjectiveThe neural mechanisms underlying the beneficial effects of a computerized cognitive training (CCT) program for improving episodic memory in older persons with mild cognitive impairment (MCI) remain unclear. This study aimed to use both functional and structural brain changes to elucidate the treatment effects of CCT on enhancing episodic memory.Design, setting, and participantsSingle-blinded, multicenter randomized controlled trial on 60 older adults with MCI in Fuzhou, China.InterventionParticipants were randomly assigned to either an 8-week 24-hour CCT program or a health education program as the control.MeasurementsClinical outcomes included changes in scores on the immediate and/or delayed recall subtests of the Chinese auditory verbal learning test (CAVLT) and rey complex figure test (CFT), and changes in gray matter volume and the functional connectivity of the posterior cingulate cortex (PCC) and hippocampus in the Papez circuit on magnetic resonance imaging.ResultsSignificant group-by-time effects showed greater improvements in both immediate and delayed recall scores of CAVLT and delayed recall scores of Rey CFT in participants receiving the CCT program compared to those in the health education program. Among the CCT participants, seed-based analyses revealed decreases in functional connectivity of the PCC and hippocampus with neural substrates in the parietal and occipital regions. The decreased PCC and precuneus connectivity were found to mediate patients’ improvements in immediate recall function.ConclusionAn 8-week CCT program was effective for improving episodic memory in older individuals with MCI. The decrease in connectivity originating from the PCC and hippocampus is suggestive of potential plastic changes in the Papez circuit, which could have alleviated the age-related compensatory mechanism. The findings of this study also shed light on expanding the content and extending the frequency and duration of the CCT program in future studies.     

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV? participants from Brazil (n?=?240), India (n?=?480), Malawi (n?=?481), Peru (n?=?239), South Africa (480), Thailand (n?=?240), and Zimbabwe (n?=?240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p?<?0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.     

Sleep onset/maintenance difficulties and cognitive function in nondemented older adults: the role of cognitive reserve

This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: ≤ 12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 ± 5.0 years (range = 71-97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.