After Alzheimer's Disease Patients Research Articles

White matter damage as a consequence of vascular dysfunction in a spontaneous mouse model of chronic mild chronic hypoperfusion with eNOS deficiency

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia after Alzheimer’s disease (AD). Currently, the mechanistic insights into the evolution and progression of VCID remain elusive. White matter change represents an invariant feature. Compelling clinical neuroimaging and pathological evidence suggest a link between white matter changes and neurodegeneration. Our prior study detected hypoperfused lesions in mice with partial deficiency of endothelial nitric oxide (eNOS) at very young age, precisely matching to those hypoperfused areas identified in preclinical AD patients. White matter tracts are particularly susceptible to the vascular damage induced by chronic hypoperfusion. Using immunohistochemistry, we detected severe demyelination in the middle-aged eNOS-deficient mice. The demyelinated areas were confined to cortical and subcortical areas including the corpus callosum and hippocampus. The intensity of demyelination correlated with behavioral deficits of gait and associative recognition memory performances. By Evans blue angiography, we detected blood–brain barrier (BBB) leakage as another early pathological change affecting frontal and parietal cortex in eNOS-deficient mice. Sodium nitrate fortified drinking water provided to young and middle-aged eNOS-deficient mice completely prevented non-perfusion, BBB leakage, and white matter pathology, indicating that impaired endothelium-derived NO signaling may have caused these pathological events. Furthermore, genome-wide transcriptomic analysis revealed altered gene clusters most related to mitochondrial respiratory pathways selectively in the white matter of young eNOS-deficient mice. Using eNOS-deficient mice, we identified BBB breakdown and hypoperfusion as the two earliest pathological events, resulting from insufficient vascular NO signaling. We speculate that the compromised BBB and mild chronic hypoperfusion trigger vascular damage, along with oxidative stress and astrogliosis, accounting for the white matter pathological changes in the eNOS-deficient mouse model. We conclude that eNOS-deficient mice represent an ideal spontaneous evolving model for studying the earliest events leading to white matter changes, which will be instrumental to future therapeutic testing of drug candidates and for targeting novel/specific vascular mechanisms contributing to VCID and AD.

A subcortical variant of dementia with Lewy bodies?

AbstractBackgroundEven though Dementia with Lewy bodies (DLB) is the second most frequent neurodegenerative disease after Alzheimer’s disease (AD), work is still needed on the definition of its clinical and radiological variants. The objective of the present work is to discuss the existence of a subcortical variant of DLB based on two previous studies. In the first study, the objective was to test the existence of a subcortical atrophy, contrasting with overall preserved cortex in DLB patients. In the second study, we described a series of DLB patients with an initial presentation including marked subcortical atrophy suggestive of normal pressure hydrocephalus (NPH).MethodIn the first study, we included 55 DLB patients and compared their cerebral volumes to those of 51 AD patients and to those of 17 matched healthy control subjects (CS). We examined the ratio of the total ventricular volume (TVV) against the total cortical volume (Cortex), extracted using freesurfer. In the second study, we retrospectively compared the profile of 21 DLB patients fulfilling the criteria of possible NPH on initial presentation, to those of 13 patients with probable NPH.ResultIn the first study, we found that DLB patients had a significantly higher TVV/Cortex ratio compared to both CS and AD patients. In the second study, we highlighted that some DLB patients have a clinical and radiological profile suggestive of NPH. DLB patients had a marked subcortical atrophy, with not significance difference in the dilatation of lateral ventricles and third ventricle compared to HPN patients, though they had a less acute callosal angle and less fourth ventricular dilatation.ConclusionDLB is characterized by a subcortical atrophy contrasting with relatively preserved cortex, so marked in some cases that it might evoke ventricular dilatation. Together the two studies suggest the existence of a subcortical variant of DLB, with a clinical presentation and marked subcortical atrophy suggestive of NPH.

Differentiating Dementia with Lewy Bodies from Alzheimer's Disease Using the Fall Risk Evaluation Questionnaire.

Objective Dementia with Lewy bodies (DLB) is the second-most common form of neurodegenerative dementia after Alzheimer's disease (AD). Falls are a vital prognostic factor in patients with dementia and are a characteristic feature of DLB. This study investigated the screening potential of the fall risk evaluation for DLB and compared it with that of AD to facilitate an accurate diagnosis. Methods We enrolled patients diagnosed with DLB (n=410) and AD (n=2,683) and categorized the participants into 3 groups depending on their physical ability, age, cognitive function, and fall events. Using the Fall Risk Index-21 (FRI-21) questionnaire, we evaluated and comparatively analyzed the fall risk between DLB and AD patients in three defined groups of participants. Results The FRI-21 score was significantly higher in DLB patients than in AD patients in every group. Using this score, we were able to distinguish between DLB and AD patients in each group. Among the three groups, the group with a young age, relatively mild cognitive dysfunction, and no fall events exhibited the best specificity for DLB (0.895). Conclusions The FRI-21 is a useful tool for screening for DLB and differentiating it from AD. This questionnaire can be used at a relatively early stage of the disease in young patients with mild cognitive dysfunction and no history of falling. These preliminary results need to be validated in an interventional study to evaluate the effectiveness of rehabilitative measures and daily environmental changes carried out to prevent falls using this tool.

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer's Disease.

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD.

PRODROMAL AND NON-PRODROMAL DEMENTIA WITH LEWY BODIES AND ALZHEIMER'S DISEASE: A MULTIMODAL MRI APPROACH

Dementia with Lewy bodies (DLB) is one of the main etiology of dementia after Alzheimer's disease (AD). Brain imaging studies have reported very few data in prodromal dementia with Lewy bodies (MCI-DLB). To focus on an earlier stage of the disease in a differential diagnostic perspective, we aimed to describe patterns of volume, perfusion, and connectivity in prodromal and non-prodromal DLB, and to assess for differences with prodromal and non-prodromal AD. We studied 112 subjects including 41 prodromal DLB patients, 15 DLB patients at the mild stage of dementia (mild-DLB), 14 prodromal AD (MCI-AD), 21 AD patients at the mild stage (mild-AD), and 21 healthy elderly controls (HC). They all underwent T1 3D MPRAGE, Asl (arterial spin labeling), and DTI MRI sequences. Voxel-wise analysis was conducted for grey matter and perfusion. The analysis of DTI consists in extending the general linear model, as implemented in SPM, to tensor images taking into account all information available in the tensor. Significant effects were identified by a correction for multiple comparisons using family-wise error and false discovery rate at p<0.05. MCI-DLB patients showed diminished GM volumes of bilateral insulae, mild-DLB patients of bilateral insulae, claustrum and putamen, MCI-AD patients of hippocampus and parahippocampal gyrus (right predominant), and mild-AD patients of temporal lobes including hippocampi. The areas of hypoperfusion were larger than atrophy, including anterior cingulate and insular areas for MCI-DLB. The areas of modifications of the tensor images included insulae, anterior cingulate and frontal regions in MCI-DLB. Using three different MRI approach, we found in all cases modifications of the insulae in DLB patients, at the stage of MCI but also mild dementia. Our results supplement previous reports by describing these early abnormalities and supports the role of insula in DLB at the early stages. Moreover it seems that focal atrophy in insula has distant consequences in MCI-DLB patients as seen in perfusion, and is the reflect of probable more diffuse lesions according to the tensor images. The next step is to better understand what is the link of these results with symptoms of DLB such as hallucinations, fluctuations, cognition, and neurovegetative symptoms.

Survival in Subcortical Vascular Dementia: Predictors and Comparison to Probable Alzheimer's Disease in a Tertiary Memory Clinic Population

Background: Subcortical vascular dementia (SVaD) is one of the most common dementias, after Alzheimer's disease (AD) dementia. Few survival analyses in SVaD patients have been reported. Methods: The dates and causes of death of 146 SVaD and 725 AD patients were included. We used the Cox proportional hazards model to compare survival between SVaD and AD patients and to explore possible factors related to survival of SVaD patients. Results: The median survival time after the onset of SVaD (109 months) was shorter than that recorded for AD (152 months). The most common cause of death in SVaD was stroke (47.1%). Factors associated with shorter survival in SVaD were late onset, male sex, worse baseline cognition, absence of hypertension and a family history of stroke. Conclusions: Stroke prevention may be important in SVaD treatment because 47.1% of SVaD patients died of stroke. A family history of stroke and absence of hypertension were associated with a shorter survival in SVaD, suggesting the existence of genetic or unknown risk factors.

NEUROINFLAMMATORY RESPONSES TO CEREBROVASCULAR DISEASE IN APP/PS1 TRANSGENIC MICE

Vascular dementia is the second most common cause of dementia after Alzheimer's disease (AD). In addition, it is estimated that almost half of all AD patients have significant cerebrovascular disease co-morbid with their AD pathology. We hypothesize that cerebrovascular disease alters the neuroinflammatory response of the brain to Alzheimer's disease pathology. We have induced two distinct cerebrovascular disease models in APP/PS1, amyloid-depositing mice. The first model is the hyperhomocysteinemia (HHCy) model that results in hemorrhagic cerebrovascular pathology. The second model is the bilateral carotid artery stenosis (BCAS) model of hypoperfusion and ischemia. We then examined the neuroinflammatory state by gene expression measurement of 30 different neuroinflammtory markers. Under normal conditions, the APP/PS1 mice with established amyloid pathology show high expression of alternative, M2a inflammatory markers including arginase 1, IL1Ra, and YM1. When cerebrovascular disease is present, there is a distinct switch in the inflammatory state toward an M1, pro-inflammatory bias including expression of IL1beta, TNFalpha and IL6. Furthermore, the presence of cerebrovascular disease with amyloid pathology results in an additive effect on memory impairment in the absence of changes in total Abeta load. Despite unchanging Abeta load, the distribution of amyloid is altered, favoring cerebrovascular deposition. Overall, our data suggests that cerebrovascular disease alters amyloid distribution and results in further cognitive impairment. This is in association with a dramatic shift in the neuroinflammatory state of the brain. We believe this data has significant implications to the treatment of dementia patients who have Alzheimer's and cerebrovascular pathologies present.

β-amyloid deposition is shifted to the vasculature and memory impairment is exacerbated when hyperhomocysteinemia is induced in APP/PS1 transgenic mice.

IntroductionVascular dementia is the second most common cause of dementia after Alzheimer’s disease (AD). In addition, it is estimated that almost half of all AD patients have significant cerebrovascular disease comorbid with their AD pathology. We hypothesized that cerebrovascular disease significantly impacts AD pathological progression.MethodsWe used a dietary model of cerebrovascular disease that relies on the induction of hyperhomocysteinemia (HHcy). HHcy is a significant clinical risk factor for stroke, cardiovascular disease and type 2 diabetes. In the present study, we induced HHcy in APP/PS1 transgenic mice.ResultsWhile total β-amyloid (Aβ) load is unchanged across groups, Congophilic amyloid deposition was decreased in the parenchyma and significantly increased in the vasculature as cerebral amyloid angiopathy (CAA; vascular amyloid deposition) in HHcy APP/PS1 mice. We also found that HHcy induced more microhemorrhages in the APP/PS1 mice than in the wild-type mice and that it switched the neuroinflammatory phenotype from an M2a biased state to an M1 biased state. Associated with these changes was an induction of the matrix metalloproteinase protein 2 (MMP2) and MMP9 systems. Interestingly, after 6 months of HHcy, the APP/PS1 mice were cognitively worse than wild-type HHcy mice or APP/PS1 mice, indicative of an additive effect of the cerebrovascular pathology and amyloid deposition.ConclusionsThese data show that cerebrovascular disease can significantly impact Aβ distribution in the brain, favoring vascular deposition. We predict that the presence of cerebrovascular disease with AD will have a significant impact on AD progression and the efficacy of therapeutics.

The high frequency of periodic limb movements in patients with Lewy body dementia

BackgroundAlthough dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD), the clinical diagnosis is frequently difficult. Because both REM sleep behavior disorders and Parkinson's disease also have alpha-synucleinopathy similar to DLB, and show an increase in periodic limb movements (PLM), we evaluated the association between DLB and PLM, which may serve as an additional information to differentiate AD and DLB. MethodsOvernight polysomnographic recordings were performed for the inpatients in our hospital who were suspected to have dementia. The quality of sleep, oxygen-desaturation index and periodic limb movements were compared among the patients clinically diagnosed with DLB, AD or as having no dementia. ResultsNine DLB patients, twelve AD patients and ten non-demented patients were enrolled in the study. The number of PLM during sleep per hour of total sleep time (PLMS index) was significantly higher in the DLB patients than the AD patients or the non-demented patients. No significant differences were found between the AD patients and the non-demented patients. To differentiate DLB from AD, a PLMS index of more than 15.0 had a sensitivity of 88.9% and a specificity of 83.3%. ConclusionsThe DLB patients exhibited a higher PLMS index than the AD patients, and this index could be clinically useful for the diagnostic differentiation of DLB from AD.

Multimodality imaging characteristics of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). Our objective was to determine whether the 11C-Pittsburgh Compound-B (PiB) retention and regional hypometabolism on positron emission tomography (PET) and regional cortical atrophy on magnetic resonance imaging (MRI) are complementary in characterizing patients with DLB and differentiating them from AD. We studied age-, gender-, and education-matched patients with a clinical diagnosis of DLB (n = 21), AD (n = 21), and cognitively normal subjects (n = 42). Hippocampal atrophy, global cortical PiB retention and occipital lobe metabolism in combination distinguished DLB from AD better than any of the measurements alone (area under the receiver operating characteristic = 0.98). Five of the DLB and AD patients who underwent autopsy were distinguished through multimodality imaging. These data demonstrate that magnetic resonance imaging and PiB positron emission tomography contribute to characterizing the distinct pathological mechanisms in patients with AD compared with DLB. Occipital and posterior parietotemporal lobe hypometabolism is a distinguishing feature of DLB and this regional hypometabolic pattern is independent of the amyloid pathology.

A comparison of F-18 FDG-PET imaging in differential diagnosis of Alzheimer's disease and dementia with Lewy body disease

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). Clinically it is characterized by attentional fluctuation, recurrent visual hallucinations and motor features of Parkinsonism, while histopathologically by cortical and sub-cortical Lewy bodies. However, due to overlapping clinical features and low sensitivity of clinical diagnostic criteria, the differential diagnosis of AD and DLB remains a major problem in clinical practice. The aim of this study was to investigate the diagnostic value of metabolism in the diagnosis of DLB and AD in comparison with [F-18] fluoro-2-deoxy-D-glucose (FDG)-PET imaging. Investigations which could help improve the accuracy of discrimination between DLB and AD would be a major advance. All subjects underwent 18F-FDG-PET and MRI. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping among DLBD, AD and NC subjects, and evaluated differences of hypometabolic regions. All PET scans be visually rated from equivalent slices, each image volume was registered to match a 18F-FDG-PET template in standard MNI (Montreal Neurological Institute) space using statistical parametric mapping. Accurate normalization is essential for quantitative pattern analysis to neurodegenerative disease; the cerebellum or pons was often used as a reference region in the MR image, which assumed no significant regional influence of physiological fluctuations for quantitative. 18F-FDG-PET revealed evidence of diffuse hypometabolism in both DLBD and AD with Parkinsonism marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, DLBD subjects also had hypometabolism in the occipital association cortex and primary visual cortex. Significant changes in hypometabolism in the volume of interest were assessed in the posterior cingulate gyrus, precuneus and parietal cortices. The severity of the decrease in metabolism in AD patients was significantly greater than in vascular dementia and frontotemporal dementia patients and controls. These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG-PET may be useful in discriminating DLBD from AD.

SU‐GG‐I‐158: A Comparison of F‐18 FDG‐PET Imaging in Differential Diagnosis of Alzheimer's Disease with Parkinsonism and Dementia with Lewy Bodies Disease

Purpose: Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). The aim of this study was to investigate the diagnostic value of metabolism in the diagnosis of DLB and AD in comparison with [F‐18]fluoro‐2‐deoxy‐D‐glucose(FDG)—PET imaging. Investigations which could help improve the accuracy of discrimination between DLB and AD would be a major advance. Methods: All Subjects underwent 18F‐FDG‐PET and MRI. We compared regional cerebral metabolic images by a voxel‐by‐voxel analysis with statistical parametric mapping (SPM) among DLBD, AD and NC subjects, and evaluated differences of hypometabolic regions. All PET scans be visually rated from equivalent slices, each image volume was registered to match a 18F‐FDG‐PET template in standard MNI (Montreal Neurological Institute) space using statistical parametric mapping. Accurate normalization is essential for quantitative pattern analysis to neurodegenerative disease; the cerebellum or pons was often used as a reference region in the MR image, which assumed no significant regional influence of physiological fluctuations for quantitative. Results: 18F‐FDG‐PET revealed evidence of diffuse hypometabolism in both DLBD and AD with Parkinsonism marked declines in association cortices with relative sparing of subcortical structures and primary somatomotor cortex, a pattern reported previously in AD. Unlike AD, DLBD subjects also had hypometabolism in the occipital association cortex and primary visual cortex. Significant changes in hypometabolism in the volume of interest were assessed in the posterior cingulate gyrus, precuneus and parietal cortices. The severity of the decrease in metabolism in AD patients was significantly greater than in vascular dementia and frontotemporal dementia patients and controls. Conclusion: These findings indicate the presence of diffuse cortical abnormalities in DLBD and suggest that FDG‐PET may be useful in discriminating DLBD from AD.

Reduced CSF CART in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). The underlying neurobiological mechanism of DLB is not fully understood and no generally accepted biomarkers are yet available for the diagnosis of DLB. In a recent MRI study, DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients. Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed selectively in neurons in the hypothalamus. Here, we found that CSF CART levels were significantly reduced by 30% in DLB patients ( n = 12) compared to controls ( n = 12) as well as to AD patients ( n = 14) using radioimmunoassay. Our preliminary results suggest that reduced CSF CART is a sign of hypothalamic dysfunction in DLB and that it may serve as a biomarker for this patient group.

P2-217: A new approach to EEG analysis in dementia with Lewy bodies

Background: Dementia with Lewy bodies (DLB) is claimed to be the second most common neurodegenerative dementia after Alzheimer’s disease (AD). The core clinical features are visual hallucinations, fluctuating cognition and parkinsonism. Fluctuating cognition is often difficult to evaluate in the clinic. In DLB, the EEG can show loss of alpha activity as the dominant rhythm and an increase in EEG power density in the delta and theta bands. One study by Walker et al (2000) correlated fluctuating cognition with greater variability in the delta domain of the quantitative EEG. In this study we aimed to investigate whether the EEG could be a way of visualising fluctuations in patients with DLB as well as if the EEG could be a useful way of distinguishing patients with DLB from patients with AD. Methods: We analysed the quantitative EEGs in 64 patients with Alzheimer’s disease, 20 patients with DLB and 54 controls from a clinical follow up programme. The parameters investigated were frequencies, variability and coherence. Results: The frequency analysis showed an increase in theta and delta activity in the DLB patients compared to both the AD patients and the controls. The variability in delta power was analysed between 2-sec intervals in parietal electrodes (P3 and P4). We found significantly greater variability even between these short epochs in the DLB patients compared to both the AD patients and the controls. The AD patients showed greater variability than the controls. (P3: p 0.001 DLB vs AD and DLB vs controls, p 0.001 AD vs controls; P4: p 0.001 DLB vs AD, DLB vs controls and AD vs controls.) The coherence analysis showed a significantly lower overall value in the alpha frequency band and a significantly higher overall value in the delta frequency band in the DLB group compared to the other two groups. (Delta: p 0.004 DLB vs AD, p 0.007 DLB vs controls; Alpha: p 0.011 DLB vs AD, p 0.016 DLB vs controls) Conclusions: In conclusion we suggest that this new approach to EEG analysis may visualise fluctuations in DLB on a second-to-second basis and might have clinical implications as guidance in the diagnosis of DLB.

P3-442: Comparison of costs of care between patients with Alzheimer's disease and dementia with Lewy bodies

Dementia with Lewy Bodies (DLB) has recently been recognized as the second most common neurodegenerative dementia after Alzheimer's disease (AD). However, studies on costs of care for dementia patients have focused almost exclusively on patients with AD, with limited effort to examine costs of DLB patients. The objectives of this study are to compare total costs of care and its major components for patients with AD or DLB. Data consisted of 170 patients with probable AD, diagnosed according to the NINDS-ADRDA criteria, and 25 patients with DLB, diagnosed according to the 1996 consensus guidelines. At study entry, all patients lived in the community and had a Folstein Mini-Mental State examination (MMSE) score≥16. Patient and informant reported on patient's use of direct medical care (hospitalizations, outpatient tests and procedures, assistive devices, and medications), direct non-medical care (home health aides, respite care, adult day care), and informal care. Patients' clinical and demographic characteristics included global cognitive status (measured by MMSE), functional capacity (measured by Blessed Dementia Rating Scale, BDRS), psychotic symptoms, behavioral problems, depressive symptoms extrapyramidal signs, comorbidities, age, and sex. Costs were compared using covariate matching methods, first matching on age and sex, then additionally on MMSE, and last additionally on BDRS. Average annual costs for caring for DLB patients ($35,143) were higher than that for AD patients ($25,129) but differences were not statistically significant. Direct non-medical costs were significantly lower ($947 vs $1,478) and indirect costs were significantly higher ($23,036 vs $17,136) for DLB patients compared to AD patients. After matching on age and sex, between-group differences for indirect costs and direct non-medical costs remained statistically significant. After additional matching on MMSE, between-group differences for indirect costs were only marginally significant, and for direct non-medical costs they were no longer statistically significant. After additional matching on functional status, between-group differences in all costs were no longer statistically significant. Apparent cost differences were largely attributed to differences in patients' cognitive and functional status. However, small sample size for DLB patients may have limited power to detect statistically significant differences in costs of care between these groups.

Race/ethnic differences in AD survival in US Alzheimer's Disease Centers

Survival after Alzheimer disease (AD) is poorly understood for patients of diverse race/ethnic groups. We examined whether nonwhite AD patients (African American, Latino, Asian, American Indian) had different rates of survival compared with white AD patients. The National Alzheimer's Coordinating Center (NACC) cataloged data from more than 30 Alzheimer's Disease Centers in the United States from 1984 to 2005. Patients aged 65 years or older with a diagnosis of possible/probable AD were included (n = 30,916). Survival was calculated using Cox proportional hazards models with a primary outcome of time to death. Secondary outcomes of this study were neuropathologic characteristics on an autopsied subsample (n = 3,017). The 30,916 AD patients in the NACC were followed up for 2.4 +/- 2.9 years (mean age 77.6 +/- 6.5 years; 65% women; 19% nonwhite [12% African American, 4% Latino, 1.5% Asian, 0.5% American Indian, and 1% other]). Median survival was 4.8 years. African American and Latino AD patients had a lower adjusted hazard for mortality compared with white AD patients (African American hazard ratio [HR] 0.85, 95% CI 0.74 to 0.96; Latino HR 0.57, 95% CI 0.46 to 0.69). Asians and American Indians had similar adjusted hazards for mortality compared with white AD patients (p > 0.10 for both). African American and Latino autopsied AD patients had similar neuropathologic characteristics compared with white AD patients with similar clinical severity. African American and Latino Alzheimer disease (AD) patients may have longer survival compared with white AD patients. Neuropathology findings did not explain survival differences by race. Determining the underlying factors behind survival differences may lead to longer survival for AD patients of all race/ethnic backgrounds.

Serum proteomic profiling of dementia with Lewy bodies: diagnostic potential of SELDI-TOF MS analysis

Dementia with Lewy bodies (DLB) is the second most common senile degenerative dementia after Alzheimer's disease (AD). The presentation of overlapping symptoms between these two disorders leads to difficulties in the determination of clinical entities. Serum samples were subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) analysis in order to identify a diagnostic marker for DLB. Four putative protein peaks (m/z 3,883, 4,964, 7,761 and 10,534) were differentially expressed in DLB patients compared to AD patients and control subjects. Receiver operating characteristics (ROC) analysis of a multivariate logistic model of the combination of three peaks (m/z 3,883, 7,761 and 10,534) exhibited the highest discriminatory ability of DLB subjects from non-DLB subjects with a sensitivity of 83.3%, a specificity of 95.8%, a positive predictive value of 90.9% and a negative predictive value of 92.0%. SELDI-TOF MS profiling, therefore, has revealed a serum signature with high diagnostic potential for DLB.

Demencia con cuerpos de Lewy y enfermedad de Alzheimer: diagnóstico diferencial mediante estudio de la inervación simpática cardíaca con MIBG

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). At present, pre-mortem diagnosis of DLB can only be made clinically using the International Consensus Criteria. However, an accurate differential diagnosis between these diseases could improve the therapeutic handling of patients with DLB, due to their supersensitivity to neuroleptic treatment and the difficult treatment of their psychotic symptoms. To assess the utility of cardiac MIBG imaging as diagnostic study for DLB, to help in the differential diagnosis with AD. Cardiac MIBG imaging was performed in 11 patients with clinical criteria of probable DLB (7 males, mean age 77 years [range 62-89 years], mean MMSE 17 [range 11-28], and in 9 patients with clinical criteria of probable AD (3 males, mean age 79 years [range 61-87 years], mean MMSE 17 [range 4-25]). Planar anterior images of the thorax were acquired at 15 minutes. (early study) and 4 hours (late study) after tracer injection. Myocardial MIBG activity was quantified by means of a heart-to-mediastinum ratio (HMR). A HMR > 1.8 was considered normal. Respect AD patients, patients with DLB showed decreased HMR in the early study (1.34 +/- 0.27 [range 1.03-1.98] vs. 1.84 +/- 0.22 [range 1.53-2.15], p<0.001) and in the late study (1.22 +/- 0.23 [range 0.95-1.75] vs. 1.73 +/- 0.08 [range 1.59-1.89], p<0.0001). Cardiac MIBG imaging could be a useful tool for differential diagnosis between DLB and AD.