Medial temporal lobe atrophy on MRI in dementia with Lewy bodies

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.     

MRI volumetric study of dementia with Lewy bodies: a comparison with AD and vascular dementia

OBJECTIVE: To compare global and regional atrophy on MRI in subjects with dementia with Lewy bodies (DLB), AD, vascular dementia (VaD), and normal aging. In addition, the relationship between APOE-epsilon4 genotype and volumetric indices was examined. METHOD: MRI-based volume measurements of the whole-brain, ventricles, frontal lobe, temporal lobe, hippocampus, and amygdala were acquired in elderly subjects with DLB (n = 27; mean age = 75.9 years), AD (n = 25; 77.2 years), VaD (n = 24; 76.9 years), and normal control subjects (n = 26; 76.2 years). RESULTS: Subjects with DLB had significantly larger temporal lobe, hippocampal, and amygdala volumes than those with AD. No significant volumetric difference between subjects with DLB and VaD was observed. Compared with control subjects, ventricular volumes were increased in all patients with dementia, though those with DLB showed a relative preservation of whole-brain volume. There were no significant differences in frontal lobe volumes between the four groups. APOE-epsilon4 status was not associated with volumetric indices. CONCLUSION: The findings support the hypothesis that DLB is associated with a relative preservation of temporal lobe structures. In the differentiation of DLB and AD, this may have important implications for diagnosis.     

Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.     

Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects

OBJECTIVE: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. METHODS: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), frontotemporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB) (n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). RESULTS: The APOE allele frequencies of this Belgian control population (epsilon 2: 6.9%; epsilon 3: 76.2%; epsilon 4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE epsilon 4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE epsilon 3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE epsilon 2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE epsilon 4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of epsilon 4 alleles in MCI and mixed dementia patients. CONCLUSIONS: This study confirmed the risk association between APOE epsilon 4 and AD. The observation that APOE epsilon 4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE epsilon 4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.     

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. Method:- A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.     

The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer's disease

BACKGROUND: Little is known about the rate of progression or associations of cognitive impairment in dementia with Lewy bodies (DLB), or the associations of accelerated decline. METHOD: Dementia patients from a case register were evaluated at baseline and 1 year follow-up using the Cambridge Assessment for Mental Disorders in the Elderly, section B (CAMCOG) and the Mini-Mental State Examination (MMSE) to determine the rate of cognitive decline. Operationalized clinical diagnoses were applied (NINCDS ADRDA for Alzheimer's disease (AD), NINCDS AIRENS for vascular dementia (VaD) and consensus criteria for DLB). RESULTS: One hundred and ninety-three patients completed annual MMSE schedules (AD, 101; DLB, 64; VaD, 38), of whom 154 completed the CAMCOG. The magnitude of cognitive decline (MMSE, 4-5 points; CAMCOG, 12-14 points) was similar in each of the dementias. The strongest predictor of accelerated cognitive decline in DLB was the apolipoprotein E4 allele (17.5 vs 8.3 points decline on the CAMCOG). CONCLUSION: Over 1 year, DLB, VaD and AD patients had similar rates of cognitive decline overall. Apolipoprotein E4 may be an important predictor of more rapid decline in DLB.     

One year follow-up of parkinsonism in dementia with Lewy bodies

The progression of parkinsonism over 1 year was evaluated in a prospective cohort of patients (n = 338), suffering from dementia with Lewy bodies (DLB), Alzheimer's disease (AD) or vascular dementia (VaD). Parkinsonism was assessed using the modified Unified Parkinson's Disease Rating Scale. Significant parkinsonism was significantly commoner in DLB sufferers (71%) than amongst patients with AD (7%) or VaD (10%). DLB patients with established parkinsonism had an annual increase in severity of 9%, but progression was more rapid (49% in 1 year) in patients with early parkinsonism. Parkinsonism was frequent at all severities in DLB patients, but usually only present in other dementias when MMSE <10.     

Medial temporal lobe width on CT scanning in Alzheimer's disease: comparison with vascular dementia, depression and dementia with Lewy bodies

A simple linear measurement of the minimum width of the medial temporal lobe (MTL) on angled CT scans has been suggested as an accurate ante-mortem marker for Alzheimer's disease (AD). To determine the clinical utility and specificity of this finding, we performed angled CT scans with 5-mm slices in 116 subjects referred to a geographically based Old Age Psychiatry service in Newcastle. Diagnoses were of NINCDS/ADRDA AD (n = 69, 36 probable and 33 possible). NINDS/AIREN vascular dementia (VaD, n = 25), consensus criteria for dementia with Lewy bodies (DLB, n = 9) and DSM-IV criteria for major depression (n = 13). Subjects were well matched for age. Minimum MTL width was significantly greater in depressed subjects (13.7 mm) compared to those with dementia, though no differences were seen within the dementia groups (AD 10.8, VaD 10.4, and DLB 10.9 mm). An MTL width below 11.5 mm had a sensitivity of 54% (56/103) and a specificity of 77% (10/13) for distinguishing dementia from depression. We conclude that a single cross-sectional measurement of MTL width on CT does not help differentiate between different types of dementia, though it may provide some supportive evidence when distinguishing depression from dementia.     

Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia

OBJECTIVES: Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a group of AD, FTD and VaD. METHODS: T1 weighted MRI images and 99mTc-HMPAO SPECT images were obtained from consecutive patients with FTD (n=21), AD (n=23) and VaD (n=20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. RESULTS: Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non-FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non-AD (VaD, FTD) patients. CONCLUSION: Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity.     

Cerebrospinal fluid phospho-tau,total tau and beta-amyloid(1-42) in the differentiation between Alzheimer's disease and vascular dementia

The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and beta-amyloid(1-42) (Abeta(1-42)). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Abeta(1-42) was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Abeta(1-42) in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.     

Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia

To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer's disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson's disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0-7 scale, Kw = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0-2.2; AD 1.4-1.6; PD 0.7-1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1-2.9) and visual-perceptual impairment (0.7-3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (-0.12 to -0.5) and relative verbal memory impairment (-0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5-3.6; DLB/AD 2.1-2.6; DLB/PD 0.8-1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.     

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.     

MRI study of caudate nucleus volume in Parkinson's disease with and without dementia with Lewy bodies and Alzheimer's disease

OBJECTIVE: To compare whole brain and caudate volume on MRI in subjects with Parkinson's disease without cognitive impairment (PD), Parkinson's disease with dementia with Lewy bodies (PD + DLB), Alzheimer's disease (AD) and normal control subjects. To examine the relationship between caudate volume and cognitive impairment, depression and movement disorder. METHOD: Whole brain and caudate volumes were segmented from volumetric 1.5-tesla magnetic resonance imaging (MRI) scans of older subjects with PD (n = 28; mean age 75.5 years), PD + DLB (n = 20; 73.0 years), AD (n = 27; 77.5 years) and normal controls (n = 35; 74.9 years). RESULTS: Subjects with AD had significantly reduced whole brain and caudate volume compared to controls and those with PD. Caudate atrophy in AD was proportionate to whole brain atrophy. There were no significant differences in whole brain or caudate volume between controls, PD and PD + DLB. There were no significant correlations between caudate volume and either global cognitive function, executive performance or processing speed. CONCLUSIONS: Caudate atrophy occurs in AD but not PD without dementia. Caudate atrophy is not regionally specific but part of generalised brain volume loss. Structural changes in the caudate, as assessed by in vivo MRI, do not appear to contribute to the cognitive impairment observed amongst patients with PD, PD + DLB or AD. Results indicate that the executive and attentional dysfunctions associated with PD and DLB are unlikely to be a direct and specific consequence of caudate atrophy as assessed on MRI.     

Inflammatory mediators in the frontal lobe of patients with mixed and vascular dementia

Vascular dementia (VaD) accounts for about 20% of all dementias, and vascular risk is a key factor in more than 40% of people with Alzheimer's disease (AD). Little is known about inflammatory processes in the brains of these individuals. We have examined inflammatory mediators (interleukin (IL)-1beta, IL-1alpha, IL-6 and tumour necrosis factor alpha) and chemokines (macrophage inflammatory protein 1, monocyte chemo-attractant protein (MCP)-1 and granulocyte macrophage colony-stimulating factor) in brain homogenates from grey and white matter of the frontal cortex (Brodmann area 9) from patients with VaD (n = 11), those with concurrent VaD and AD (mixed dementia; n = 8) and from age-matched controls (n = 13) using ELISA assays. We found a dramatic reduction of MCP-1 levels in the grey matter in VaD and mixed dementia in comparison to controls (55 and 66%, respectively). IL-6 decreases were also observed in the grey matter of VaD and mixed dementia (72 and 71%, respectively), with a more modest decrease (30%) in the white matter of patients with VaD or mixed dementia. In the first study to examine the status of inflammatory mediators in a brain region severely affected by white-matter lesions, our findings highlight - in contrast to previous reports in AD - that patients at the later stage of VaD or mixed dementia have a significantly attenuated neuro-inflammatory response.     

Profiles of matrix metalloproteinases and their inhibitors in plasma of patients with dementia

BACKGROUND: Matrix metalloproteinases (MMPs) are elevated in the brain tissue of patients with dementia and may play a role in the pathophysiology of dementia. MMP-9 and tissue inhibitors of MMPs (TIMPs) are elevated in postmortem brain tissue of patients with Alzheimer's disease (AD). In a previous study we showed that circulating levels of MMP-9 are elevated in AD patients. The aim of the present study was to examine circulating levels of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 in the plasma of patients with mild cognitive impairment (MCI), AD, vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD), to determine, whether plasma profiles of MMPs and TIMPs differ in various types of dementia. METHODS: Gelatinolytic activity (MMP-2 and MMP-9) was measured in all plasma samples by zymography. Levels of MMP-2, MMP-9, MMP-1 as well as TIMP-1 and TIMP-2 were measured by ELISA. RESULTS: We found constitutive expression of MMP-1, -2 and -9 as well as TIMP-1 and -2 in all the samples investigated. As shown previously, MMP-9 was significantly elevated in the plasma of AD patients (p = 0.004) as compared to controls and MCI patients. Plasma levels of TIMP-1 were significantly lower in VD samples as compared to all other groups. Levels of TIMP-2 were significantly lower in patients with FTD as compared to AD, VaD and MCI patients. There were no significant changes of MMP-1 and MMP-2 levels in the samples. CONCLUSION: These findings suggest that circulating levels of MMP-9, TIMP-1 and TIMP-2 and changes in the MMP/TIMP balance in plasma differ in various types of dementia.     

Frequency of early and late-onset dementias in a Japanese memory disorders clinic

The aim of this study was to compare the diagnostic profiles of patients with early (age<65 years) and late (age>or=65 years) onset of dementia in a memory disorders clinic in Japan. A total of 512 consecutive memory clinic patients were evaluated using clinical information and results of examinations. Diagnosis of dementia was made according to DSM-III-R, and that of subtypes according to standard diagnostic criteria. A total of 464 patients met the criteria for dementia. Amongst late-onset patients (n=430), Alzheimer's disease (AD) (48.1%) was the most frequent cause of dementia, followed by AD with cerebrovascular disease (CVD) (31.4%), vascular dementia (VaD) (9.1%), dementia with Lewy bodies (DLB) (3.7%), frontotemporal lobar degeneration (FTLD) (1.6%), and others (5.8%). On the contrary, amongst early onset patients (n=34), the most common dementia diagnosis was AD (38.2%), followed by VaD (23.5%), FTLD (14.7%), AD with CVD (5.9%), DLB (2.9%), and others (17.6%). FTLD and VaD were significantly more common in the early onset group. All patients, but one, with DLB and Parkinson's disease dementia were late-onset. The relative frequencies of AD, VaD, and DLB in our series are consistent with epidemiologic findings in several Western countries; however, the frequency of FTLD is not consistent with the previous findings presenting high frequency in late-onset patients in some Western countries.     

Simple standardised neuropsychological assessments aid in the differential diagnosis of dementia with Lewy bodies from Alzheimer's disease and vascular dementia

Consecutive patients from a dementia case register received a standardised evaluation which incorporated a neuropsychological assessment with the Cambridge Assessment for disorders in the elderly (CAMCOG). Operationalised clinical diagnoses were made (consensus criteria for dementia with Lewy bodies, DLB; NINCDS- ADRDA for Alzheimer's disease, AD, NINCDS AIRENS for vascular dementia, VaD). Two-hundred and twenty-eight patients were studied (DLB 54, AD102, VaD 72). DLB patients had significantly better performance on recent memory than AD patients, but more impaired visuospatial praxis. DLB patients also had significantly better recent memory than those with VaD. Optimal cut-off points for the recent memory:praxis ratio achieved good discrimination between DLB and both other dementias.     

Comparison between Alzheimer's disease and vascular dementia: implications for treatment

Virtually 90% of the elderly with late-onset dementia exhibit neuropathological features consistent with Alzheimer's disease (AD), vascular dementia (VaD) or dementia with Lewy bodies (DLB), alone or in combination. Both AD and DLB reveal extensive senile plaques containing amyloid beta whereas neurofibrillary tangles evident as tau pathology are fewer in DLB, which also bears diffuse cortical Lewy bodies. Interestingly, however, there is considerable overlap between AD and VaD in terms of both risk factors and pathology. Cholinergic deficits are also encountered in VaD, which like AD may respond to cholinergic therapy. Cerebrovascular pathology, ischemic brain damage and autonomic dysregulation resulting in cerebral hypoperfusion appears fundamental in the pathogenesis of late-onset dementias.     

Cognitive and functional decline in African Americans with VaD, AD, and stroke without dementia.

OBJECTIVE: To compare the rates of cognitive and functional decline in African American patients diagnosed at baseline with vascular dementia (VaD) (n = 79), AD (n = 113), or stroke without dementia (SWD) (n = 56) and followed for up to 7 years with annual neuropsychological and other examinations. METHODS: Study patients were diagnosed using established criteria for dementia and were administered cognitive screening, functional screening, and neuropsychological measures. Baseline dementia severity was rated using the Clinical Dementia Rating Scale. Random effects modeling was used to examine rates of decline and to compare the rates of decline in the three groups. RESULTS: Both patients with VaD and those with AD showed significant cognitive and functional decline during follow-up; patients with VaD declined at a slower rate than patients with AD; and patients diagnosed with SWD at baseline did not show cognitive or functional decline during follow-up. CONCLUSIONS: Patients with VaD decline at a slower rate than patients with AD. Patients who do not meet criteria for dementia soon after stroke may not be at high risk for developing dementia. Future studies are needed to follow VaD patients with longitudinal, specialized MR protocols, concurrent neuropsychological examinations, and neuropathologic examination to determine possible neuroimaging predictors of progressive cognitive and functional decline and to assess the contribution of Alzheimer's pathology to decline in patients diagnosed with VaD.     

Soluble adhesion molecules and angiotensin-converting enzyme in dementia

We aimed to determine plasma and cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and platelet endothelial cell adhesion molecule-1 (sPECAM-1) as surrogate markers for endothelial cell activation in clinically diagnosed patients with Alzheimer's disease (AD, n=260), dementia with Lewy bodies (DLB, n=39) and non-demented controls (n=34). Plasma sICAM-1 and sPECAM-1 were higher and CSF sVCAM-1 were lower in AD and DLB patients than in controls (p<0.001). DLB patients had higher CSF sICAM-1, but lower CSF sVCAM-1 (p<0.001). No difference in ACE levels was found between the dementia groups and controls. In controls and AD patients CSF sICAM and sVCAM-1 strongly correlated with each other and with blood barrier permeability whereas in DLB group these correlations were weaker. The observed patterns in adhesion molecules may reflect distinctions in the pathophysiological basis of their generation in dementia patients.