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Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients.

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.

Objective: The objective of this study was to describe the relationship among cognitive test performance, psychological symptoms, and subjective cognitive difficulties in older adults with atherosclerotic vascular disease., Method: Participants were 80 adults over the age of 55 with an unequivocal diagnosis of atherosclerotic vascular disease. Participants completed measures of neuropsychological functioning, psychological symptoms, and two measures of subjective cognitive difficulties., Results: Psychological symptoms were most strongly associated with higher levels of reported cognitive difficulties. Overall neuropsychological functioning was modestly related to subjective cognitive difficulties but did not remain significant after controlling for psychological symptoms., Conclusions: In this sample of older adults with atherosclerotic vascular disease, self-reported cognitive difficulties were most strongly related to overall level of psychological distress and not to actual cognitive test scores. Therefore, psychological factors may play an important role in the phenomenon of self-perceived cognitive decline in geriatric populations.

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.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

Hachinski and co-workers have used the term vascular cognitive impairment-no dementia (VaCIND) to represent the earliest stages of cognitive decline associated with vascular changes [Neurology 57 (4) (2001) 714]. However, the neuropsychological profile of vascular CIND remains unclear. Twenty-five healthy elders, 29 individuals at risk for cerebrovascular disease (R-CVD), 18 individuals with VaCIND, and 26 individuals with vascular dementia (VaD) were examined to determine whether patterns of neuropsychological assessment performance can assist in the differentiation of patients at varying levels of risk and severity for cerebrovascular disease and VaD. The R-CVD group performed within normal expectations on most cognitive measures as compared to the elderly control sample and published clinical norms. Relative to elderly controls, the VaCIND group demonstrated significant difficulties on measures of cognitive flexibility, verbal retrieval, and verbal recognition memory, but not on measures of confrontational naming or verbal fluency. The VaD group was impaired on all cognitive measures assessed. The current findings suggest that poor cognitive flexibility and verbal retrieval in the context of preserved function in other domains may characterize the prodromal stage of VaD.

The purpose of this study was to examine the course and predictors of functional decline among patients with vascular dementia (VaD). Twenty-eight VaD patients completed three tests of executive functions and underwent MRI scanning to generate quantitative ratings of subcortical neuropathology at a baseline evaluation. The caregiver-rated Lawton and Brody Activities of Daily Living Questionnaire was used to estimate instrumental activities of daily living (IADLs) at the baseline evaluation and at a 1 year follow-up. We hypothesized that: (a) IADLs would decline significantly over the course of 1 year, and (b) baseline performance on executive tasks and subcortical neuropathology would predict IADL impairment at 1 year follow-up, even after accounting for global cognitive dysfunction. A paired samples t-test demonstrated that IADLs declined significantly over the course of 1 year, and regression analyses revealed that baseline performance on executive tasks was a significant predictor of IADLs at the 1 year follow-up, even after accounting for global cognitive dysfunction. Contrary to our expectation, subcortical neuropathology did not explain unique variance in IADLs after accounting for executive dysfunction. These findings demonstrate that baseline executive dysfunction is a significant and powerful predictor of future functional decline in individuals with VaD.

White matter hyperintensities (WMHs) are frequently found on MRI studies of vascular dementia (VaD) patients. As several studies have demonstrated that WMHs are often associated with severity of illness, cognitive impairment, and functional decline, the accurate and reliable measurement of WMHs on MRI is an important, yet often overlooked, prerequisite for accurate interpretation of neuroimaging studies. Using a sample of 39 VaD patients, we evaluated the reliability and validity of a visual ordinal rating scale and a computer-mediated thresholding technique to evaluate WMHs. Results indicated the computer-mediated technique had slightly stronger inter-rater reliability than the visual ordinal rating scale. Furthermore, the computer-mediated thresholding technique was correlated with measures of neuropsychological functioning believed to be compromised in VaD (i.e., psychomotor speed, executive functioning) while the visual rating scale was not. Results suggest that this computer-mediated thresholding technique is superior to visual ratings of WMHs.

Objective: To determine whether demographic data, dementia severity, functional status, whole brain volume (WBV), or subcortical hyperintensity volume (SH) predict subsequent cognitive decline in vascular dementia (VaD)., Background: The identification of variables that accurately predict progressive cognitive decline in dementia has important clinical implications., Methods: A cohort of 30 patients with VaD completed neurologic and neuropsychologic examinations and magnetic resonance imaging of the brain at baseline and again after 12 months. All participants met clinical and research criteria for VaD according to standard guidelines. Change scores were computed for measures of verbal fluency, verbal learning, and visual learning. Potential correlates of cognitive change included age, education, score on the Hachinski scale, WBV, SH, and functional ability., Results: As a group, lower WBV and lower Hachinski score correlated with decline in verbal fluency and visual learning, whereas lower Hachinski score correlated with decline in verbal learning. However, when subdivided by disease type, this pattern held only for individuals with evidence of a cortical stroke at baseline. No clinical variables correlated with cognitive decline among individuals without a cortical infarction., Conclusions: Assessment of cognitive decline in VaD should be guided by dementia subtype, with particular attention directed at severity of cerebral atrophy rather than classic symptoms of infarction.

Background: The Dementia Rating Scale (DRS) is a common measure of cognitive function, but its sensitivity to identify deficits across cognitive domains in vascular dementia (VaD) remains unclear., Methods: We compared the sensitivity and specificity of two recommended cutoff scores of the DRS. Thirty-eight patients diagnosed with VaD participated in the current study., Results: The original recommendations resulted in poor sensitivity for the DRS total score and attention, construction, and memory subscales. The more recent recommendations greatly improved the sensitivity of the subscales and the total DRS score, but resulted in decreased specificity. Correlations between the specific DRS subscales and criterion measures of cognitive function revealed good convergent and divergent validity for most subscales., Conclusions: The DRS is a valid measure of cognitive dysfunction in VaD, but clinicians should consider using the more recent recommendations developed for AD to determine impaired performances in VaD., (Copyright 2003 S. Karger AG, Basel)

Background: Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD)., Methods: 30 patients diagnosed with VaD, based upon NINDS-AIREN and DSM-IV criteria, were randomized and treated with either 500 mg of citicoline or placebo twice per day. Patients were assessed at baseline, and at 6, and 12 months on a battery of neurocognitive tests. Neuroimaging measures of total brain volume and subcortical/periventricular hyperintensity (SH) volume on magnetic resonance imaging (MRI) were collected at baseline and the 12-month follow-up., Results: The citicoline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up., Conclusions: The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study., (Copyright 2003 S. Karger AG, Basel)

The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 +/- 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive-psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive-psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD.

The relationship of behavioral disturbance and dementia severity to activities of daily living (ADLs) in vascular dementia (VaD) was examined in baseline data for 29 VaD patients. A series of stepwise regression analyses was conducted to examine the extent to which dementia severity, apathy, disinhibition, and executive dysfunction predict ADLs (total, basic, and instrumental). For total ADLs, apathy accounted for 36% of the variance and dementia severity accounted for an additional 15%. For basic ADLs, apathy accounted for 27% of the variance. Dementia severity, executive dysfunction, and disinhibition were not significantly associated with basic ADLs. For instrumental ADLs, dementia severity accounted for 37% of the variance and apathy accounted for an additional 14%. These findings highlight the importance of apathy as an independent factor associated with functional independence beyond general cognitive abilities.

The present study examined the serial position effect in 2 subgroups of individuals with vascular dementia (VaD). Nineteen individuals with mild VaD and 17 individuals with moderate VaD were administered the California Verbal Learning Test. Both groups were impaired on a general memory measure, and the moderately impaired group demonstrated significantly poorer recall than the mildly impaired group on the first learning trial and on total learning across trials. In addition, individuals with mild dementia demonstrated an intact primacy and recency effect, whereas individuals with moderate dementia demonstrated neither primacy nor recency effects. The latter findings are consistent with studies examining the serial position effect in other dementia populations, and suggests that the absence of primacy and recency effects in more advanced dementia may occur regardless of dementia type.

In the present study, we examined the relationships between ratings on the Global Deterioration Scale (GDS) and activities of daily living and cognitive function in 39 individuals with vascular dementia (VaD). The results of the study revealed significant correlations between GDS rating and performance on cognitive tests, including memory and overall cognitive ability. In addition, the GDS was significantly related to ratings of instrumental activities of daily living. Comparisons between patients with VaD with GDS scores between 4 and 6 (n = 21) and patients with scores between 2 and 3 (n = 18) revealed greater cognitive and functional deficits in the group with higher GDS scores. Further, the GDS score accurately classified 87% of the patients with VaD. These findings provide support for the validity of the GDS in general staging of dementia severity of VaD.

Background: The relationship between subcortical hyperintensity (SH) on magnetic resonance imaging (MRI), cortical perfusion on single photon emission computed tomography (SPECT), and cognitive function is not well understood. The authors examined these relationships in individuals with vascular dementia (VaD), paying particular attention to frontal lobe function to determine whether the presence of SH on MRI was associated with frontal hypoperfusion on SPECT, which in turn would be associated with impairments of executive-attention function., Methods: Patients with vascular dementia (n = 26) were assessed on neurocognitive tests and brain MRI and SPECT. SH volume was quantified from the axial T2-weighted fluid attenuated inversion recovery MRI. Total counts of activation across voxels for 12 cortical regions of interest were determined from SPECT. Perfusion ratios of both total cortical and frontal activation relative to cerebellum activation were derived, and regression analyses were performed to determine the relationships between cognitive, MRI, and SPECT indices., Results: SH volume on MRI was significantly associated with frontal lobe perfusion, but not with global cortical perfusion as measured by SPECT. Frontal lobe perfusion did not consistently correlate with performance on measures of executive-attention function, although both total and frontal perfusion ratios were significantly associated with other cognitive functions., Conclusions: These results suggest that a functional "disconnection" between the frontal lobes and subcortical structures does not fully account for the magnitude of global cognitive impairment in VaD. Cortical perfusion as measured by SPECT appears to be associated with cognitive performance, but not specifically executive-attention dysfunction. Additional studies are needed to further examine the relationship between subcortical and cortical function in VaD.

Objective: To determine the relation between subcortical hyperintensities (SHs) visible on magnetic resonance imaging and executive function among patients with vascular dementia., Background: The relation between SHs and executive dysfunction is not well understood, because studies have varied widely in methodology and have produced conflicting results., Method: We examined the relation between SHs (expressed as a percentage of total brain volume, not including ventricular volume) and six tests of executive function in a well-defined group of 24 individuals with vascular dementia. Executive tests were divided in two groups: Attention/Speed and Abstraction/Problem Solving. Bivariate correlations were computed between individual neuropsychological variables and SHs., Results: Results showed significant bivariate correlations between SHs and three of the four tests in the Attention/Speed domain. Subcortical hyperintensities shared virtually no association with performance on tests in the Abstraction/Problem-Solving domain., Conclusions: The finding that SHs are significantly associated with psychomotor slowing and attentional dysfunction is consistent with what is known about the behavioral manifestations of subcortical disease. More detailed investigations of the regional distribution of SHs as well as measures of atrophy, hypoperfusion, and hypometabolism may be necessary to accurately characterize the complex relation between vascular disease and different aspects of executive dysfunction.