The Difference of Verbal Fluency Task Performance between Alzheimer's Disease and Subcortical Vascular Dementia: CREDOS (Clinical Research Center for Dementia of South Korea) Study

BACKGROUND: The verbal fluency test consists of two separate tests of semantic fluency and phonemic fluency. The performance patterns of these tests differ with the type of dementia. We studied the patterns of verbal fluency between Alzheimer's disease (AD) and subcortical vascular dementia (SVaD), and assessed the clinical utility of these tests. METHODS: The 1,475 selected participants comprised 73 normal control subjects, 673 patients with amnestic mild cognitive impairment (aMCI), 535 AD patients, 42 patients with subcortical vascular mild cognitive impairment (svMCI), and 152 SVaD patients. We analyzed the z-score for the total number of animal items as a semantic fluency index and the z-score of the phonemic total score as a phonemic fluency index. RESULTS: The performance of semantic fluency was lower than that of phonemic fluency in all groups. The SVaD group showed the worst scores and abnormal performances on both tests, while the AD group presented abnormal performance only for semantic fluency. Dividing the patients with dementia according to severity revealed a different pattern between AD and SVaD for the clinical dementia rating (CDR) stage of 0.5. The performance of the AD group declined gradually with CDR. However, the SVaD group performed very poorly in both tests even for very mild dementia (CDR stage of 0.5). The aMCI and svMCI groups exhibited similar performance patterns. CONCLUSIONS: The pattern of semantic and phonemic fluency was not clinically useful at the MCI stage, but it could be helpful in differentiating AD and SVaD in the early stage of dementia.

A Comparison of Apolipoprotein E Polymorphism in Alzheimer's Disease and Subcortical Vascular Dementia in Koreans

BACKGROUND AND PURPOSE: The apolipoprotein E (Apo E) epsilon4 allele is known to be a risk factor for Alzheimer's disease (AD). However, there are debates about the relationship between Apo E epsilon4 frequency and subcortical vascular dementia (SVaD). We compared the frequency of the Apo E epsilon4 allele in AD and SVaD in Koreans. METHODS: The study was comprised of 400 subjects who visited the Dementia Clinic at Daegu Catholic University from July 2007 to December 2011. Neuropsychological tests, a brain MRI, and blood laboratory tests were performed on all subjects. Two hundred and ninety subjects were AD, 32 subjects were SVaD and 78 subjects were normal. The diagnosis for SVaD was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and Erkinjuntti criteria, and the diagnosis for AD was based on the DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's disease and Related Disorders Association criteria. Apo E polymorphism was genotyped in all subjects. RESULTS: The Apo E epsilon4 allele frequency was 17.4% in AD, 10.9% in SVaD and 8.3% in the normal group (p=0.03). The odds ratio (OR) after age adjustment for AD conferred to the Apo E epsilon4 was 2.04 (p=0.04). But, the OR for SVaD conferred to the Apo E epsilon4 allele was 1.34 (p=0.62), indicating that the Apo E epsilon4 allele does not significantly confer the risk of SVaD. CONCLUSIONS: Apo E epsilon4 is a reliable predictor of AD but has modest efficacy for predicting SVaD in Koreans.

Diffusion Tensor Imaging Changes Correlate with Clinical Progression in Vascular Mild Cognitive Impairment and Vascular Dementia of Subcortical Type

BACKGROUND: Cerebral small vessel disease (SVD) induces vascular cognitive impairment (VCI) such as subcortical vascular dementia (SVaD) and subcortical vascular mild cognitive impairment (svMCI). We compared MRI parameters between SVaD and svMCI and determined which MRI parameters best correlated with cognitive function and disability on cross-sectional and longitudinal analyses within them. METHODS: Twenty-four patients with SVaD and twelve with svMCI were recruited. They underwent multimodal MRIs including fluid-attenuated inversion recovery lesion load, lacunar infarct number, and fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI), neuropsychological testing, Sum of Boxes of Clinical Dementia Rating Scale (CDR-SB), Barthel Index, and the Korean version of a Geriatric Depression Scale (GDS-K). Seventeen patients were retested after 20 months for a brain MRI and clinical evaluation. RESULTS: There were significant differences in average MD and peak height of MD histograms within normal-appearing brain tissue (NABT) between SVaD and svMCI patients. In the cross-sectional analysis, average MD within NABT significantly correlated with the composite neuropsychology score (r=-0.80, p<0.001), the composite executive function score (r=-0.67, p< 0.001), and the CDR-SB (r=0.54, p=0.001), and the Barthel Index correlated with peak heights of the MD histograms (r=0.37, p=0.03) in NABT. Changes of CDR-SB was associated with changes of average MD within WMH (r=0.57, p=0.02), and changes of GDS-K was associated with changes of WMH volume (r=0.51, p=0.04) on a longitudinal scale. CONCLUSIONS: DTI parameters in NABT correlated with cognitive impairment and disability in VCI associated with SVD. Clinical progression of SVD was associated with some increment of WML volume and ultrastructural changes in WMH.

Altered Consciousness After Acute Lacunar Infarction of the Corona Radiata in Patients With Severe White Matter Change

With an increasing proportion of the elderly, dementia due to severe cerebral white matter change is frequently observed. Because these patients cannot express their symptoms effectively, the recognition of stroke can be delayed. In addition, clinical characteristics of their stroke might be different. We reported on three patients with severe leukoaraiosis, who exhibited altered consciousness after acute lacunar infarction in the corona radiata. This clinico-radiological discrepancy may have resulted from different susceptibility to ischemia in patients with severe white matter change.

The Prevalence and Severity of Neuropsychiatric Symptoms in Alzheimer's Disease and Subcortical Vascular Dementia : the CREDOS Study

OBJECTIVES: This study aimed to compare the prevalence and severity of clinically relevant neuropsychiatric symptoms between subjects with Alzheimer's disease (AD) and subcortical vascular dementia (SVD). METHODS: The CREDOS (Clinical Research for Dementia Of South Korea) is a multicenter longitudinal cohort study organized to evaluate the long-term outcome of dementia patients. Out of a total 3,080 subjects, we selected 1,392 AD subjects and 247 SVD subjects with mild to moderate levels of dementia. The Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating Scale (CDR), and CDR sum of box scores were used for evaluation. RESULTS: After controlling for severity of dementia and duration of education, SVD subjects had relatively more symptoms of apathy compared to AD subjects (OR : 1.397, p=0.025). SVD subjects also had relatively higher NPI composite scores in the apathy domain compared to AD subjects, after controlling for severity of dementia, age and duration of education (F=7.88, p=0.01). Subjects with moderate levels of dementia had more frequent and severe neuropsychiatric symptoms compared to those with mild dementia. CONCLUSION: Symptoms of apathy were more prevalent and severe in subjects with SVD, compared to subjects with AD.

Effect of Physical Disability on Instrumental Activities of Daily Living in Alzheimer's Disease, Amnestic Mild Cognitive Impairment (MCI), and Vascular Dementia and Vascular MCI of Subcortical Type

BACKGROUND: Physical disability may result in some impairment of the score for Instrumental Activities of Daily Living (IADL). The aim of this study was to evaluate the effect of physical disability on IADL in patients with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), subcortical vascular dementia (SVD), and vascular mild cognitive impairment of the subcortical type (svMCI). METHODS: Fifty-six patients with AD, 30 with SVD, 27 with aMCI, and 21 with svMCI were recruited consecutively from a memory clinic. Informants for the subjects completed a Korean version of the IADL (K-IADL). In addition, the informants were asked to choose the cause of each dependent activity of K-IADL from the following: cognitive impairment, physical disability, or both. The cause of the physical disability was defined as being focal neurologic symptoms, other physical disease, or both. RESULTS: Compared to AD patients, SVD patients had higher K-IADL scores [2.02+/-0.80 (mean+/-SD) vs. 1.45+/-0.90, p<0.01] and focal neurologic signs (FNS; 8.0+/-5.8 vs. 0.0+/-0.0, p<0.001), and lower Barthel Index scores (14.7+/-5.1 vs. 19.6+/-1.2, p<0.001). Patients with svMCI had higher FNS (3.8+/-4.5 vs. 0.0+/-0.0, p<0.001) compared to those with aMCI. The most common cause of dependency of activities in K-IADL was cognitive impairment in AD, aMCI, and svMCI patients, and the combined effect of cognitive impairment and physical disability in those with SVD. The cause of physical disability was FNS in 96% of SVD patients and in all patients with svMCI. CONCLUSIONS: The effects of FNS as well as cognitive impairment should be considered when measuring the IADL of the patients with SVD or svMCI.

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment

BACKGROUND AND PURPOSE: The most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring. METHODS: The subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the study's inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring. RESULTS: The prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05]. CONCLUSIONS: It was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP.

Differences of Tc-99m HMPAO SPECT Imaging in the Early Stage of Subcortical Vascular Dementia Compared with Alzheimer's Disease / 핵의학분자영상

PURPOSE: The aim of this study is to assess the specific patterns of regional cerebral blood flow (rCBF) in patients with the early stage of subcortical vascular dementia (SVaD) and Alzheimer's disease (AD) using Tc-99m HMPAO SPECT, and to compare the differences between the two conditions. MATERIALS AND METHODS: Sixteen SVaD, 46 AD and 12 control subjects participated in this study. We included the patients with SVaD and AD according to NINCDS-ADRDA and NINDS-AIREN criteria. They were all matched for age, education and clinical dementia rating scores. Three groups were evaluated by Tc-99m HMPAO SPECT using statistical parametric mapping (SPM) for measuring rCBF. The SPECT data of patients with SVaD and AD were compared with those of normal control subjects and then compared with each other. RESULTS: SPM analysis of the SPECT image showed significant perfusion deficits on the right temporal region and thalamus, left insula and superior temporal gyrus, both cingulate gyri and frontal subgyri in patients with SVaD and on the left supramarginal gyrus, superior temporal gyrus, postcentral gyrus and inferior parietal lobule, right fugiform gyrus and both cingulate gyri in AD compared with control subjects (uncorrected p<0.01). SVaD patients revealed significant hypoperfusion in the right parahippocampal gyrus with cingulated gyrus, left insula and both frontal subgyral regions compared with AD (uncorrected p<0.01). CONCLUSION: Our study shows characteristic and different pattern of perfusion deficits in patients with SVaD and AD, and these results may be helpful to discriminate the two conditions in the early stage of illness.

Usefulness of Seoul Verbal Learning Test in Differential Diagnosis of Alzheimer's Disease and Subcortical Vascular Dementia

BACKGROUND: The Seoul Verbal Learning Test (SVLT) is a relatively brief test of verbal learning and memory, which is used to examine dementia patients when a more comprehensive memory assessment is not feasible or when serial testing is desired. The aim of this study was to investigate the pattern of the SVLT performance and its usefulness in making a differential diagnosis between Alzheimer's disease (AD) and subcortical vascular dementia (SVD). METHODS: The SVLT was administered to 15 younger controls, 12 elderly controls, 84 probable AD and 53 SVD patients who met the DSM-IV criteria for dementia. In order to determine the difference of the SVLT parameters between AD and SVD according to the disease severity, the subjects were first grouped into mild dementia (CDR 1 or less) and advanced dementia (CDR2), then the parameters were compared. RESULTS: Pattern analysis of the SVLT performance in subjects with AD and SVD revealed that the mild AD subjects recalled fewer words in trial 2, had a lower discrimination index, a lower combination memory score and more recognition of semantically-unrelated distracter items. In advanced cases, with the exception of combination memory score, there were no differences between the groups in terms of the overall learning or the discrimination index. CONCLUSIONS: Although SVLT has limited differential diagnostic value in advanced cases, in mild cases, pattern analysis of the SVLT performance is a useful tool for discriminating mild AD from SVD. Therefore, a further clinical study should be promising.

Clinical Implication of "Closing-in" in Patients with Dementia

BACKGROUND: "Closing-in" phenomenon is defined as a tendency to close in the model while copying tasks. This unique phenomenon is one of the constructional apraxia often observed in dementia, especially in Alzheimer's disease (AD). The aim of this study is to investigate the usefulness of "closing-in" in the differential diagnosis of AD and subcortical vascular dementia, and to clarify what the associated factors to this phenomenon are. METHODS: Based on copying data of alternating square and triangle in younger control, we operationally defined "closing-in". "Closing-in" in copied figure was classified into three types: overlap, adherent and near types. With this criteria, we analyzed the incidence of "closing-in" in younger control (N=30), elderly control (N=22), AD (N=64), and subcortical vascular dementia (N=31). RESULTS: Compared with subcortical vascular dementia, AD patients had a significantly higher occurrence of "closing-in" phenomenon. Among "closing-in" type, overlap and adherent type was exclusively occurred in AD. A discriminant analysis, calculated by combining results obtained by AD, showed that symptom onsets with age. Korean Mini-Mental State Examination, Clinical Dementia Rating Scale, Rey-Osterrieth Complex Figure Test were significantly correlated with "closing-in". In EEG mapping, though AD patients with apraxia had significantly lower alpha spectra power in all fields, there is no statistical difference between patients with closing-in and those without. CONCLUSIONS: This study suggests that "closing-in" phenomenon was a phase- and AD-specific useful tool for differential diagnosis with subcortical vascular dementia. Moreover, overlap and adherent subtypes of "closing-in" was highly specific in AD, so further clinical study may be promising.

The Different Patterns of Behavioral Derangements in Subcortical Vascular Dementia and Alzheimer's Disease: Evaluated by the Korean Version of the Neuropsychiatric Inventory

BACKGROUND: The neuropsychiatric derangements in dementing patients are common and troublesome in their managements. The purpose of this study is to compare the behavioral changes in patients with subcortical vascular dementia (SVaD) and to those in patients with Alzheimer's disease (AD) by using the Korean version of the neuropsychiatric inventory (K-NPI). METHODS: The K-NPI was administrated to the close caregivers of 19 patients with AD (who met the criteria of the NINCDS-ADRDA for probable AD) and 14 patients with SvaD (who met the criteria of the NINDS-AIREN criteria for probable or possible VaD). Groups were matched for age, education and dementia severity. We evaluated the prevalence, the composite score (frequency X severity) of each behavioral domain in K-NPI between two groups. RESULTS: The most common behavioral disturbances were anxiety (63%) in AD and apathy/indifference (93%) in SVaD. Patients with SVaD had significantly greater total K-NPI scores than patients with AD and exhibited apathy/indifference, agitation/aggression and anxiety more frequently. Composite score of apathy/indifference over 4.7 point discriminates between AD and SVaD with accuracy of 75.8%. CONCLUSIONS: The K-NPI provides behavioral profiles that differentiate patients with SVaD from patients with AD. Patients with SVaD are more behaviorally disturbed. Clinicians need to pay more attention to the behavioral disturbances when managing the patients with SVaD.