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1.  Stability of Neuropsychological Performance in Anorexia Nervosa 
Background
We investigated the stability of neuropsychological performance and eating disorder (EDO) symptoms before, immediately after, and 2 years after inpatient treatment. We also examined relationships between neuropsychological and EDO measures.
Methods
Sixteen women who were admitted for inpatient treatment of anorexia nervosa participated in three evaluations: (1) at admission to the hospital, (2) at discharge, and (3) at a follow-up exam approximately two years after discharge.
Results
Body mass index increased significantly from each testing session to the next. Endorsement of eating disorder symptoms was significantly decreased at discharge and at follow-up compared to admission. In terms of cognitive performance, total scores on a brief neuropsychological battery (RBANS) were significantly greater at follow-up than at admission. We found no relationships between EDO symptoms and cognitive function at follow-up.
Conclusions
The current findings suggest that EDO symptoms and cognitive performance in anorexia nervosa patients can show improvement as long as two years after hospitalization, but there is no evidence that EDO symptoms are related to neuropsychological performance at that time.
doi:10.1080/10401230701844836
PMCID: PMC3808087  PMID: 18297581
anorexia nervosa; neuropsychological functioning; body mass index
2.  Short-term practice effects in amnestic mild cognitive impairment: implications for diagnosis and treatment 
Background
Practice effects have been widely reported in healthy older adults, but these improvements due to repeat exposure to test materials have been more equivocal in individuals with mild cognitive impairment (MCI).
Methods
The current study examined short-term practice effects in MCI by repeating a brief battery of cognitive tests across one week in 59 older adults with amnestic MCI and 62 intact older adults.
Results
Participants with amnestic MCI showed significantly greater improvements on two delayed recall measures (p < 0.01) compared to intact peers. All other practice effects were comparable between these two groups. Practice effects significantly improved scores in the MCI group so that 49% of them were reclassified as “intact” after one week, whereas the other 51% remained “stable” as MCI. Secondary analyses indicated the MCI-Intact group demonstrated larger practice effects on two memory measures than their peers (p < 0.01).
Conclusions
These results continue to inform us about the nature of memory deficits in MCI, and could have implications for the diagnosis and possible treatment of this amnestic condition.
doi:10.1017/S1041610208007254
PMCID: PMC3789513  PMID: 18405398
mild cognitive impairment; practice effects; repeat testing
3.  Patterns of serotonergic antidepressant usage in prodromal Huntington disease☆ 
Psychiatry research  2012;196(0):309-314.
Antidepressant usage in prodromal Huntington Disease (HD) remains uncharacterized, despite its relevance in designing experiments, studying outcomes of HD, and evaluating the efficacy of therapeutic interventions. We searched baseline medication logs of 787 prodromal HD and 215 healthy comparison (HC) participants for antidepressant use. Descriptive and mixed-effects logistic regression modeling characterized usage across participants. At baseline, approximately one in five prodromal HD participants took antidepressants. Of those, the vast majority took serotonergic antidepressants (selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)). Significantly more prodromal HD participants used serotonergic antidepressants than their HC counterparts. Because of the prevalence of these medications, further analyses focused on this group alone. Mixed-effects logistic regression modeling revealed significant relationships of both closer proximity to diagnosis and female sex with greater likelihood to be prescribed a serotonergic antidepressant. More prodromal HD participants took antidepressants in general and specifically the subclass of serotonergic antidepressants than their at-risk counterparts, particularly when they were closer to predicted time of conversion to manifest HD. These propensities must be considered in studies of prodromal HD participants.
doi:10.1016/j.psychres.2011.09.005
PMCID: PMC3763706  PMID: 22397915
Psychiatric; Antidepressant; Neuroprotection; Clinical trials; SSRI
4.  Gender differences in neuropsychological performance in individuals with atherosclerosis: Impact of vascular function 
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.
doi:10.1080/13803391003757841
PMCID: PMC3592378  PMID: 20512721
Gender; Cognition; Vascular disease; Neuropsychology; Vascular function
5.  Anxious symptoms and cognitive function in non-demented elderly adults: an inverse relationship 
Objective
The goals of this study were to determine the relationship between anxious symptoms and cognitive functioning in a non-demented, community-dwelling elderly sample (N = 48), and to determine the effect of depressive symptoms upon this relationship.
Methods
Anxious and depressive symptoms were assessed using Symptom Checklist 90-Revised. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status.
Results
Results indicated that while both cognitive functioning and anxious symptoms were within normal limits in this sample, anxious symptoms showed a significant, inverse relationship with global cognitive function [r(47) = −.400, p = .005]. In addition, specific relationships were noted between severity of anxious symptoms and visuospatial/constructional ability as well as immediate and delayed memory. With regard to the secondary objective, both anxiety and depressive symptoms together accounted for the highest level of variance [R2 = .175, F(2, 45) = 4.786, p = .013] compared to anxiety [R2(47) = .160, p = .005] and depression [R2(47) = .106, p = .024] alone. Nevertheless, neither anxious nor depressive symptoms emerged as a unique correlate with cognitive ability [r(47)= −.278, p = .058; r(48)= −.136, p = .363, respectively].
Conclusion
This study demonstrates that subthreshold anxiety symptoms and cognitive functioning are significantly related even among generally healthy older adults whose cognitive ability and severity of anxious symptoms are within broad normal limits. These findings have implications both for clinical care of elderly patients, as well as for cognitive research studies utilizing this population.
doi:10.1002/gps.2785
PMCID: PMC3391343  PMID: 21919061
anxiety; cognitive function; elderly
6.  Obsessive and Compulsive Symptoms in Prediagnosed Huntington’s Disease 
The Journal of clinical psychiatry  2008;69(11):1758-1765.
Objective
Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington’s disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease.
Method
The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non–gene-expanded controls from the Neurobiological Predictors of Huntington’s Disease (PREDICTHD)study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as “near-to-onset” (< 9 estimated years to onset), “mid-to-onset” (9–15 years to onset), and “far-to-onset” (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender.
Results
All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying.
Conclusion
Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status.
PMCID: PMC3658314  PMID: 19012814
7.  Vascular smooth muscle function is associated with initiation and processing speed in patients with atherosclerotic vascular disease 
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.
doi:10.1017/S1355617708080697
PMCID: PMC3597121  PMID: 18577282
Vascular dementia; Subcortical vascular dementia; Neuropsychology; Atherosclerosis; Aging; Vascular endothelium-dependent relaxation
8.  Cerebral Blood Flow and Neuropsychological Functioning in Elderly Vascular Disease Patients 
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.
doi:10.1080/13803395.2011.630653
PMCID: PMC3582376  PMID: 22149630
9.  Practice effects predict cognitive outcome in amnestic Mild Cognitive Impairment 
Objective
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.
Design
Longitudinal, observational design following participants across one year.
Setting
Community-based cohort.
Participants
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).
Measurements
Neuropsychological tests.
Results
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.
Conclusions
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.
doi:10.1097/JGP.0b013e318209dd3a
PMCID: PMC3202689  PMID: 22024617
Mild Cognitive Impairment; practice effects; dementia
10.  Increased frequency of first episode poststroke depression following discontinuation of escitalopram 
Background and Purpose
To compare escitalopram, problem-solving therapy (PST), and placebo, to prevent poststroke depression during 6 months after discontinuation of treatment.
Methods
We examined for depression, 33 patients assigned to placebo, 34 to escitalopram, and 41 to PST.
Results
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.
Conclusions
Discontinuation of escitalopram may increase poststroke depressive symptoms.
doi:10.1161/STROKEAHA.111.626507
PMCID: PMC3223021  PMID: 21868736
stroke; depression
11.  Evaluation of Older Persons with Mild Cognitive Deficits: Potential Utility of Magnetic Resonance Imaging 
Annals of Clinical Psychiatry  2008;20(4):204-208.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1080/10401230802437530
PMCID: PMC3392192  PMID: 19034752
Cognition; Imaging; Aging; Memory
12.  The RBANS Effort Index: Base rates in geriatric samples 
Applied neuropsychology  2011;18(1):11-17.
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.
doi:10.1080/09084282.2010.523354
PMCID: PMC3074382  PMID: 21390895
symptom validity testing; RBANS; geriatric assessment
13.  The Trail Making Test in Prodromal Huntington Disease: Contributions of Disease Progression to Test Performance 
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.
doi:10.1080/13803395.2010.541228
PMCID: PMC3159183  PMID: 21302170
Huntington disease; cognition; motor; psychiatric; neurodegenerative
14.  Predicting cognitive change within domains 
The Clinical neuropsychologist  2010;24(5):779-792.
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.
doi:10.1080/13854041003627795
PMCID: PMC2893275  PMID: 20358479
Predicting cognition; standardized based regression
15.  Self-Paced Timing Detects and Tracks Change in Prodromal Huntington Disease 
Neuropsychology  2010;24(4):435-442.
Objective
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1037/a0018905
PMCID: PMC2900808  PMID: 20604618
Basal Ganglia; tapping; clinical trials; cognition; isochronous serial interval production
16.  Predicting Cognitive Change in Older Adults: The Relative Contribution of Practice Effects 
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.
doi:10.1093/arclin/acp105
PMCID: PMC2819829  PMID: 20064816
Predicting cognition; Practice effects
17.  Vascular Health and Cognitive Function in Older Adults with Cardiovascular Disease 
Artery research  2008;2(1):35-43.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.artres.2008.01.001
PMCID: PMC3004172  PMID: 21179381
Cardiovascular Disease; vascular function; age; endothelium; neurocognitive performance
18.  The Indiana Faces in Places Test: Preliminary Findings on a New Visuospatial Memory Test in Patients with Mild Cognitive Impairment 
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.
doi:10.1093/arclin/acp050
PMCID: PMC2755831  PMID: 19679593
Mild cognitive impairment; Visual memory; Face memory; Test–retest reliability
19.  Sex Differences in Parietal Lobe Morphology: Relationship to Mental Rotation Performance 
Brain and cognition  2008;69(3):451-459.
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.
doi:10.1016/j.bandc.2008.09.004
PMCID: PMC2680714  PMID: 18980790
sex differences; mental rotation; parietal lobe; spatial ability
20.  Endothelial Function and White Matter Hyperintensities in Older Adults With Cardiovascular Disease 
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1161/01.STR.0000254517.04275.3f
PMCID: PMC2748266  PMID: 17204686
cardiovascular disease; endothelium; magnetic resonance; white matter disease
21.  Cognitive predictors of functional decline in vascular dementia 
SUMMARY
Background
This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year.
Methods
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.
Results
Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively.
Conclusions
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.
doi:10.1002/gps.1556
PMCID: PMC2746410  PMID: 16906630
activities of daily living (ADLs); vascular dementia (VaD); functional decline; neuropsychology; cognition; memory; executive function; Dementia Rating Scale (DRS)
22.  Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial 
Context
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.
Objective
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).
Results
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.
Conclusions
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.
Trial Registration
clinicaltrials.gov Identifier: NCT00071643
doi:10.1001/jama.299.20.2391
PMCID: PMC2743160  PMID: 18505948
23.  Decisional Capacity for Research Participation in Individuals with Mild Cognitive Impairment 
OBJECTIVES
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).
DESIGN
Cross-sectional.
SETTING
Research center, medical center, or patient’s home.
PARTICIPANTS
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).
MEASUREMENTS
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.
RESULTS
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.
CONCLUSION
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.
doi:10.1111/j.1532-5415.2008.01752.x
PMCID: PMC2724182  PMID: 18482298
mild cognitive impairment; memory; executive function; cognition; decision analysis; informed consent
24.  Practice effects in the prediction of long-term cognitive outcome in three patient samples: A novel prognostic index 
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.
doi:10.1016/j.acn.2006.08.013
PMCID: PMC1847360  PMID: 17142007
practice effects; cognitive outcome; Mild Cognitive Impairment; HIV; Huntington’s disease
25.  Neuropsychological Correlates of Normal Variation in Emotional Response to Visual Stimuli 
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.
doi:10.1097/01.nmd.0000254482.44985.f6
PMCID: PMC2099574  PMID: 17299297
Emotion; induced mood; neuropsychological tests; Wisconsin Card Sorting test; Rey Complex Figure Test

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