This study was conducted to assess gender differences in cognition in elderly individuals (N = 88; 38 women, 50 men) with atherosclerotic vascular disease (AVD) and to determine whether these were attributable to differences in vascular health. Assessments included neuropsychological testing and measurement of forearm vascular function using venous occlusion plethysmography. There was a significant female advantage on multiple neuropsychological tests. This gender effect was reduced somewhat but remained significant when controlling for education and vascular function. Our study suggests that gender differences in cognition persist into older age and are not primarily due to gender differences in vascular health.
Gender; Cognition; Vascular disease; Neuropsychology; Vascular function
We previously reported a relationship between forearm resistance vessel function and global neuropsychological performance in patients with atherosclerotic vascular disease (AVD). This study was conducted to determine the relationships among vascular smooth muscle function, endothelial function, and initiation and processing speed in this sample. Participants were 80 individuals with AVD. Resistance vessel function was measured before and after infusion of vasoactive agents. Neuropsychological assessment included measures of estimated premorbid cognitive function, current global cognitive function, initiation, and processing speed. Vascular smooth muscle function was significantly associated with the initiation/processing speed composite score [R-Square Change = .152; F Change (1,71) = 16.61; p < .001], above and beyond the variance accounted for by age, education, premorbid cognitive function, and endothelium-dependent vascular function. This relationship remained significant when controlling for current level of global cognitive functioning and 10 vascular risk factors. Endothelium-dependent vascular function was not significantly associated with test performance. Decreased vascular smooth muscle function in forearm resistance vessels was significantly associated with relatively poor initiation and processing speed in individuals with AVD. With additional research, measures of vascular function might become useful in the early identification of those individuals at greatest risk for vascular-related cognitive dysfunction.
Vascular dementia; Subcortical vascular dementia; Neuropsychology; Atherosclerosis; Aging; Vascular endothelium-dependent relaxation
This study was designed to determine the relationships between PET-based quantitative measures of cerebral blood flow and cerebrovascular reserve and neuropsychological functioning in elderly individuals with atherosclerotic vascular disease. It was hypothesized that cerebrovascular function would be significantly associated with neuropsychological functioning. Results showed that both baseline global cerebral blood flow and cerebrovascular reserve were significantly associated with global neuropsychological functioning, when controlling for age and sex. Cerebrovascular reserve was additionally associated with performance on measures of memory and attention. Additional research is needed to determine whether measures of cerebral blood flow can be used to predict cognitive decline.
Practice effects on cognitive tests have been shown to further characterize patients with amnestic Mild Cognitive Impairment (aMCI), and may provide predictive information about cognitive change across time. We tested the hypothesis that a loss of practice effects would portend a worse prognosis in aMCI.
Longitudinal, observational design following participants across one year.
Three groups of older adults: 1. cognitively intact (n=57), 2. aMCI with large practice effects across one week (MCI+PE, n=25), and 3. aMCI with minimal practice effects across one week (MCI−PE, n=26).
After controlling for age and baseline cognitive differences, the MCI−PE group performed significantly worse than the other groups after one year on measures of immediate memory, delayed memory, language, and overall cognition.
Although these results need to be replicated in larger samples, the loss of short-term practice effects portends a worse prognosis in patients with aMCI.
Mild Cognitive Impairment; practice effects; dementia
Background and Purpose
To compare escitalopram, problem-solving therapy (PST), and placebo, to prevent poststroke depression during 6 months after discontinuation of treatment.
We examined for depression, 33 patients assigned to placebo, 34 to escitalopram, and 41 to PST.
After controlling for age, gender, prior mood disorder, and severity of stroke, new onset major depression and Hamilton Depression scores were significantly higher 6 months after escitalopram was discontinued, compared to the PST or placebo groups.
Discontinuation of escitalopram may increase poststroke depressive symptoms.
This study evaluated brain volumes in healthy older subjects without dementia who presented with memory complaints. The objective was to examine cortical volumes in relation to cognitive performance among patients who do not have dementia, but who do have mild cognitive deficits.
Fifteen participants were evaluated (mean age = 71.8 ± 6.2). Brain structure was measured via high-resolution magnetic resonance imaging to quantify gray and white matter volumes. Volumetric measures were assessed relative to cognitive function in separate regression models controlling for total cerebral volume. Reported here are measures of global cognitive performance using the Mattis Dementia Rating Scale (DRS) in relation to volumetric measures.
Baseline MMSE scores ranged from 27 to 30 (mean = 29.3; SD = 0.9). After controlling for total cerebral volume, we observed that lower white matter volume in the temporal lobe [F(1,14) = 5.72, p = 0.03] was associated with lower performance on the Mattis Dementia Rating Scale (DRS).
Structural imaging may help provide useful clinical information in the context of mild cognitive decline. Currently, the diagnosis of dementia relies on longitudinal measures of cognition. Future studies will help determine whether the addition of brain imaging may enhance diagnostic certainty as well as predict long-term outcome.
Cognition; Imaging; Aging; Memory
The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer’s disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cut-off scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer’s disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in 3 of the 4 clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia.
symptom validity testing; RBANS; geriatric assessment
We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9–15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.
Huntington disease; cognition; motor; psychiatric; neurodegenerative
Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs.
Predicting cognition; standardized based regression
This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC).
At baseline, participants in two groups (747 pr-HD: 188 NC) listened to tones presented at 550ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and various other demographic factors.
Pr-HD participants showed significantly less timing precision than NC. Cross-sectional comparison of pr-HD and NC participants showed a significant performance difference on two administration conditions of the task (dominant hand: p<.0001; alternating thumbs: p<.0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t=−11.14,df=920, p<.0001; alternating thumbs: t=−11.32, df=918, p<.0001), even considering demographic and experience variables. Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and that decline rate increases with estimated proximity to diagnosis in both conditions (dominant hand: t=−2.85,df=417, p=.0045; alternating thumbs: t=−3.56, df= 445, p=.0004). Effect sizes based on adjusted mean annual change ranged from −0.34 to 0.25 in the longitudinal model.
The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically-mediated improvement or maintenance of function.
Basal Ganglia; tapping; clinical trials; cognition; isochronous serial interval production
Assessing cognitive change in older adults is a common use of neuropsychological services, and neuropsychologists have utilized several strategies to determine if a change is “real,” “reliable,” and “meaningful.” Although standardized regression-based (SRB) prediction formulas may be useful in determining change, SRBs have not been widely applied to older adults. The current study sought to develop SRB formulas on a group of 127 community-dwelling older adults for several widely used neuropsychological measures. In addition to baseline test scores and demographic information, the current study also examined the role of short-term practice effects in predicting test scores after 1 year. Consistent with prior research on younger adults, baseline test performances were the strongest predictors of future test performances, accounting for 25%–58% of the variance. Short-term practice effects significantly added to the predictability of all nine of the cognitive tests examined (3%–22%). Future studies should continue extending SRB methodology for older adults, and the inclusion of practice effects appears to add to the prediction of future cognition.
Predicting cognition; Practice effects
We hypothesized that changes in vascular flow dynamics resulting from age and cardiovascular disease (CVD) would correlate to neurocognitive capacities, even in adults screened to exclude dementia and neurological disease. We studied endothelial-dependent as well as endothelial-independent brachial responses in older adults with CVD to study the associations of vascular responses with cognition. Comprehensive neurocognitive testing was used to discern which specific cognitive domain(s) correlated to the vascular responses.
Eighty-eight independent, community-dwelling older adults (70.02+7.67 years) with mild to severe CVD were recruited. Enrollees were thoroughly screened to exclude neurological disease and dementia. Flow-mediated (endothelial-dependent) and nitroglycerin-mediated (endothelial-independent) brachial artery responses were assessed using 2-d ultrasound. Cognitive functioning was assessed using comprehensive neuropsychological testing. Linear regression analyses were used to evaluate the relationships between the endothelial-dependent and endothelial-independent vascular flow dynamics and specific domains of neurocognitive function.
Endothelial-dependent and endothelial-independent brachial artery responses both correlated with neurocognitive testing indices. The strongest independent relationship was between endothelial function and measures of attention-executive functioning.
Endothelial-dependent and endothelial-independent vascular responsiveness correlate with neurocognitive performance among older CVD patients, particularly in the attention-executive domain. While further study is needed to substantiate causal relationships, our data demonstrate that brachial responses serve as important markers of risk for common neurocognitive changes. Learning and behavior-modifying therapeutic strategies that compensate for such common, insidious neurocognitive limitations will likely improve caregiving efficacy.
Cardiovascular Disease; vascular function; age; endothelium; neurocognitive performance
Memory assessment is an important component of a neuropsychological evaluation, but far fewer visual than verbal memory instruments are available. We examined the preliminary psychometric properties and clinical utility of a novel, motor-free paper and pencil visuospatial memory test, the Indiana faces in places test (IFIPT). The IFIPT and general neuropsychological performance were assessed in 36 adults with amnestic mild cognitive impairment (aMCI) and 113 older adults with no cognitive impairment at baseline, 1 week, and 1 year. The IFIPT is a visual memory test with 10 faces paired with spatial locations (three learning trials and non-cued delayed recall). Results showed that MCI participants scored lower than controls on several variables, most notably total learning (p < .001 at all three time points), delayed recall (baseline p = .03, 1 week p < .001, 1 year p < .001), and false-positive errors (range p = .03 to <0.001). The IFIPT showed similar test–retest reliability at 1-week and 1-year follow-up to other neuropsychological tests (r = 0.71–0.84 for MCI and 0.53–0.72 for controls). Diagnostic accuracy was modest for this sample (areas under the receiver operating characteristic curve between 0.64 and 0.66). Preliminary psychometric analyses support further study of the IFIPT. The measure showed evidence of clinical utility by demonstrating group differences between this sample of healthy adults and those with MCI.
Mild cognitive impairment; Visual memory; Face memory; Test–retest reliability
Structural magnetic resonance imaging (MRI) studies of the human brain have reported evidence for sexual dimorphism. In addition to sex differences in overall cerebral volume, differences in the proportion of gray matter (GM) to white matter (WM) volume have been observed, particularly in the parietal lobe. To our knowledge there have been no studies examining the relationship between the sex differences in parietal lobe structure and function. The parietal lobe is thought to be involved in spatial ability, and particularly involved in mental rotation. The purpose of this study is to examine whether sex differences in parietal lobe structure are present, and if present to relate these differences to performance on the Mental Rotations Test (MRT). We found that women had proportionately greater gray matter volume in the parietal lobe compared to men, and this morphologic difference was disadvantageous for women in terms of performance on the MRT. In contrast, we found that men compared to women had proportionately greater parietal lobe surface area, and this morphologic difference was associated with a performance advantage for men on mental rotation. These findings support the possibility that the sexual dimorphism in the structure of the parietal lobe is a neurobiological substrate for the sex difference in performance on the Mental Rotations Test.
sex differences; mental rotation; parietal lobe; spatial ability
Background and Purpose
The presence of white matter hyperintensities on brain MRI is common among elderly individuals. Previous research suggests that cardiovascular risk factors are associated with increased white matter hyperintensities. Examining the role of direct physiological measures of vascular function will help to clarify the vascular mechanisms related to white matter hyperintensities. The aim of the present study was to examine the association between endothelial-dependent and endothelial-independent vasodilatation and white matter hyperintensity volume.
Twenty-five older adults with a range of cardiovascular diseases underwent brain MRI and completed assessments of blood vessel integrity using endothelial-dependent and independent flow-mediated dilation of the brachial artery. A semi-automated pixel-based method was used to quantify total brain volume and white matter hyperintensity volume, with white matter hyperintensity volume corrected for total brain volume. The association between measures of flow-mediated dilation and log-transformed white matter hyperintensities was examined.
Correlation analysis revealed that endothelial-dependent vasodilatation was significantly and inversely associated with white matter hyperintensity volume. In contrast, endothelial-independent vasodilatation was not associated with white matter hyperintensities. Neither endothelial-dependent nor endothelial-independent vasodilatation was associated with total brain volume.
These data provide preliminary evidence that the integrity of the vascular endothelium is associated with white matter hyperintensities in older adults with cardiovascular disease. Impaired vascular function may be one mechanism that contributes to the development of white matter hyperintensities in the brain. Additional longitudinal research combining measures of vessel function, neuroimaging and cognition will be helpful in clarifying this potential mechanism.
cardiovascular disease; endothelium; magnetic resonance; white matter disease
This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year.
Twenty-four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant-based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow-up assessment was conducted one-year post-baseline.
Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively.
Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes.
activities of daily living (ADLs); vascular dementia (VaD); functional decline; neuropsychology; cognition; memory; executive function; Dementia Rating Scale (DRS)
Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal.
To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication.
Design, Setting, and Participants
A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n=59) with placebo (n=58), and a nonblinded problem-solving therapy group (n=59).
Main Outcome Measures
The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressivelike episode or minor depression (ie, research criteria).
Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 min or cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4–8.2; P<.001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4–3.5; P<.001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2–3.9; P=.007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8–1.5; P=.51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups.
In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis.
clinicaltrials.gov Identifier: NCT00071643
To assess decisional capacity performance and the neuropsychological correlates of such performance to better understand higher-level instrumental activities of daily living in individuals with mild cognitive impairment (MCI).
Research center, medical center, or patient’s home.
Forty participants with MCI and 40 cognitively normal older controls (NCs) aged 60 to 90 (mean age ± standard deviation 73.3 ± 6.6; 54% female).
Capacity to provide informed consent for a hypothetical, but ecologically valid, clinical trial was assessed using the MacArthur Competence Assessment Tool for Clinical Research. Neuropsychological functioning was assessed using a comprehensive protocol.
Adjusted between-group comparisons yielded significant differences for most decisional capacity indices examined, including Understanding (P = .001; NC>MCI) and Reasoning (P = .002; NC>MCI). Post hoc analyses revealed that participants with MCI who were categorized as capable of providing informed consent according to expert raters had higher levels of education than those who were categorized as incapable.
The findings suggest that many individuals with MCI perform differently on a measure of decisional capacity than their NC peers and that participants with MCI who are incapable of providing informed consent on a hypothetical and complex clinical trial are less educated. These findings are consistent with prior studies documenting functional and financial skill difficulties in individuals with MCI.
mild cognitive impairment; memory; executive function; cognition; decision analysis; informed consent
Practice effects, defined as improvements in cognitive test performance due to repeated exposure to the test materials, have traditionally been viewed as sources of error. However, they might provide useful information for predicting cognitive outcome. The current study used three separate patient samples (older adults with mild cognitive impairments, individuals who were HIV +, individuals with Huntington’s disease) to examine the relationship between practice effects and cognitive functioning at a later point. Across all three samples, practice effects accounted for as much as 31 to 83% of the variance in the follow-up cognitive scores, after controlling for baseline cognitive functioning. If these findings can be replicated in other patients with neurodegenerative disorders, clinicians and researchers may be able to develop predictive models to identify the individuals who are most likely to demonstrate continued cognitive decline across time. The ability to utilize practice effects data would add a simple, convenient, and non-invasive marker for monitoring an individual patient’s cognitive status. Additionally, this prognostic index could be used to offer interventions to patients who are in the earliest stages of progressive neurodegenerative disorders.
practice effects; cognitive outcome; Mild Cognitive Impairment; HIV; Huntington’s disease
Although the neural substrates of induced emotion have been the focus of numerous investigations, the factors related to individual variation in emotional experience have rarely been investigated in older adults. Twenty-six older normal subjects (mean age, 54) were shown color slides to elicit emotions of sadness, fear, or happiness and asked to rate the intensity of their emotional responses. Subjects who experienced negative emotion most intensely showed relative impairment on every aspect of the Wisconsin Card Sorting Test. Intense positive emotion was associated with relatively impaired performance on the Rey Complex Figure Test. The volume of frontal brain structures, however, was not associated with emotion responses. Hemisphere-specific executive dysfunction was associated with greater intensity of emotional experience in normal older subjects. The role of these differences in intensity of induced emotion and impairment in executive function in daily social and vocational activity should be investigated.
Emotion; induced mood; neuropsychological tests; Wisconsin Card Sorting test; Rey Complex Figure Test
Studies have shown that individuals with psychiatric or general medical illness can benefit from interventions designed to enhance decisional capacity for research informed consent. In some cases, interventions have been rather lengthy or complex. The current study was designed to determine whether a brief intervention could improve decisional capacity in people with schizophrenia. Thirty individuals with schizophrenia and 30 healthy comparison participants were presented with a hypothetical research scenario. Decisional capacity was assessed with the MacArthur Competence Assessment Tool–Clinical Research version. Those with schizophrenia received a brief intervention aimed at improving understanding of the research protocol, after which decisional capacity was reassessed. A neuropsychological battery and symptom rating scales were also administered. At baseline, the schizophrenia group earned significantly lower scores than the comparison group on 2 aspects of decisional capacity (understanding, appreciation). At follow-up, the schizophrenia group had improved significantly on understanding and was no longer significantly different from the comparison group on any of the 4 dimensions of decisional capacity. Follow-up analyses also showed a significant effect of the intervention on a subset of the schizophrenia group who had performed most poorly at baseline. Participants with schizophrenia earned significantly lower scores than those in the comparison group across multiple neuropsychological domains. These findings add to the existing literature indicating that brief interventions can improve decisional capacity in individuals with schizophrenia, despite the fact that the illness typically causes significant cognitive dysfunction. The use of such interventions will enable a larger number of people with schizophrenia to make informed decisions regarding research participation.
informed consent; decisional capacity; ethics; schizophrenia