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AD Cases (ad + case)
Selected AbstractsOptimizing Coding and Reimbursement to Improve Management of Alzheimer's Disease and Related DementiasJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2002Howard Fillit MD The objectives of this study were to review the diagnostic, International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM), diagnosis related groups (DRGs), and common procedural terminology (CPT) coding and reimbursement issues (including Medicare Part B reimbursement for physicians) encountered in caring for patients with Alzheimer's disease and related dementias (ADRD); to review the implications of these policies for the long-term clinical management of the patient with ADRD; and to provide recommendations for promoting appropriate recognition and reimbursement for clinical services provided to ADRD patients. Relevant English-language articles identified from MEDLINE about ADRD prevalence estimates; disease morbidity and mortality; diagnostic coding practices for ADRD; and Medicare, Medicaid, and managed care organization data on diagnostic coding and reimbursement were reviewed. Alzheimer's disease (AD) is grossly undercoded. Few AD cases are recognized at an early stage. Only 13% of a group of patients receiving the AD therapy donepezil had AD as the primary diagnosis, and AD is rarely included as a primary or secondary DRG diagnosis when the condition precipitating admission to the hospital is caused by AD. In addition, AD is often not mentioned on death certificates, although it may be the proximate cause of death. There is only one ICD-9-CM code for AD,331.0,and no clinical modification codes, despite numerous complications that can be directly attributed to AD. Medicare carriers consider ICD-9 codes for senile dementia (290 series) to be mental health codes and pay them at a lower rate than medical codes. DRG coding is biased against recognition of ADRD as an acute, admitting diagnosis. The CPT code system is an impediment to quality of care for ADRD patients because the complex, time-intensive services ADRD patients require are not adequately, if at all, reimbursed. Also, physicians treating significant numbers of AD patients are at greater risk of audit if they submit a high frequency of complex codes. AD is grossly undercoded in acute hospital and outpatient care settings because of failure to diagnose, limitations of the coding system, and reimbursement issues. Such undercoding leads to a lack of recognition of the effect of AD and its complications on clinical care and impedes the development of better care management. We recommend continuing physician education on the importance of early diagnosis and care management of AD and its documentation through appropriate coding, expansion of the current ICD-9-CM codes for AD, more appropriate use of DRG coding for ADRD, recognition of the need for time-intensive services by ADRD patients that result in a higher frequency of use of complex CPT codes, and reimbursement for CPT codes that cover ADRD care management services. [source] A, aggregation and possible implications in Alzheimer's disease pathogenesisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2009Prashant R. Bharadwaj ,,Introduction ,,Amyloid Structure ,,Mechanism of Amyloid aggregation ,,A,: a natively unfolded protein? ,,Ambiguities in synthetic Ab studies ,,Formation of Amyloid plaques ,,Role of Ab in AD Pathogenesis ,,Conclusion Abstract Amyloid , protein (A,) has been associated with Alzheimer's disease (AD) because it is a major component of the extracellular plaque found in AD brains. Increased A, levels correlate with the cognitive decline observed in AD. Sporadic AD cases are thought to be chiefly associated with lack of A, clearance from the brain, unlike familial AD which shows increased A, production. A, aggregation leading to deposition is an essential event in AD. However, the factors involved in A, aggregation and accumulation in sporadic AD have not been completely characterized. This review summarizes studies that have examined the factors that affect A, aggregation and toxicity. By necessity these are studies that are performed with recombinant-derived or chemically synthesized A,. The studies therefore are not done in animals but in cell culture, which includes neuronal cells, other mammalian cells and, in some cases, non-mammalian cells that also appear susceptible to A, toxicity. An understanding of A, oligomerization may lead to better strategies to prevent AD. [source] BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice,JOURNAL OF NEUROCHEMISTRY, Issue 6 2006Kouhei Nishitomi Abstract Accumulation of amyloid beta peptide (Abeta) in brain is a hallmark of Alzheimer's disease (AD). Inhibition of beta-site amyloid precursor protein (APP)-cleaving enzyme-1 (BACE1), the enzyme that initiates Abeta production, and other Abeta-lowering strategies are commonly tested in transgenic mice overexpressing mutant APP. However, sporadic AD cases, which represent the majority of AD patients, are free from the mutation and do not necessarily have overproduction of APP. In addition, the commonly used Swedish mutant APP alters APP cleavage. Therefore, testing Abeta-lowering strategies in transgenic mice may not be optimal. In this study, we investigated the impact of BACE1 inhibition in non-transgenic mice with physiologically relevant APP expression. Existing Abeta ELISAs are either relatively insensitive to mouse Abeta or not specific to full-length Abeta. A newly developed ELISA detected a significant reduction of full-length soluble Abeta 1,40 in mice with the BACE1 homozygous gene deletion or BACE1 inhibitor treatment, while the level of x-40 Abeta was moderately reduced due to detection of non-full-length Abeta and compensatory activation of alpha-secretase. These results confirmed the feasibility of Abeta reduction through BACE1 inhibition under physiological conditions. Studies using our new ELISA in non-transgenic mice provide more accurate evaluation of Abeta-reducing strategies than was previously feasible. [source] Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's diseaseJOURNAL OF PINEAL RESEARCH, Issue 1 2005Egemen Savaskan Abstract:, The aim of the present study was to identify the distribution of the second melatonin receptor (MT2) in the human hippocampus of elderly controls and Alzheimer's disease (AD) patients. This is the first report of immunohistochemical MT2 localization in the human hippocampus both in control and AD cases. The specificity of the MT2 antibody was ascertained by fluorescence microscopy using the anti-MT2 antibody in HEK 293 cells expressing recombinant MT2, in immunoblot experiments on membranes from MT2 expressing cells, and, finally, by immunoprecipitation experiments of the native MT2. MT2 immunoreactivity was studied in the hippocampus of 16 elderly control and 16 AD cases. In controls, MT2 was localized in pyramidal neurons of the hippocampal subfields CA1-4 and in some granular neurons of the stratum granulosum. The overall intensity of the MT2 staining was distinctly decreased in AD cases. The results indicate that MT2 may be involved in mediating the effects of melatonin in the human hippocampus, and this mechanism may be heavily impaired in AD. [source] Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificityNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2004Y. Fujino Ballooned neurones (BNs) are one of the pathological hallmarks of several neurodegenerative diseases, including Pick's disease, corticobasal degeneration and argyrophilic grain disease (AGD). They have also been described in Alzheimer disease (AD), but the frequency of BNs in AD has not been systematically addressed. In the present study, immunohistochemistry for ,B-crystallin was used as a sensitive method to detect BNs to determine the frequency of BNs in the limbic lobe in AD. At least a few BNs were detected in the limbic lobe of virtually all AD cases, and their density correlated with Braak stage, as well as the density of neurofibrillary tangles and senile plaques in the limbic lobe. The density of BN tended to be greater in AD cases with concurrent AGD than in pure AD. Given the high prevalence of AD in brain banks for neurodegenerative disease and the frequent presence of BNs in these areas with ,B-crystallin immunohistochemistry, the present findings further indicate that BNs confined to the limbic lobe lack specificity in diagnostic neuropathology. [source] APOE,4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of A, proteinNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2003K. Chalmers The relative amounts of amyloid ,-protein (A,) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic and environmental determinants are still unclear, as are the functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E (ApoE), influence the risk of developing AD and of deposition of A, within the brain. We examined the relationship between the APOE genotype and the relative extent of accumulation of A, as plaques within the cerebral parenchyma and in cortical blood vessels in the form of cerebral amyloid angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly, neurologically normal controls of which 19 had CAA without other neuropathological features of AD. In the AD cases, we also assessed whether the severity of CAA was related to the age of onset and duration of dementia, risk factors for atherosclerotic vascular disease, and histologically demonstrable cerebral in-farcts or foci of haemorrhage. The APOE genotype was determined by a standard polymerase chain reaction-based method. Paraffin sections of frontal, temporal and parietal lobes were immunolabelled for A, and the parenchymal A, load (total A, minus vessel-associated A,) was quantified by computer-assisted image analysis. CAA severity was scored for cortical and leptomeningeal vessels. The relevant clinical data were obtained from the database of the South West Brain Bank. In AD, we found the severity of CAA to be strongly associated with the number of ,4 alleles (P < 0.0001) but the parenchymal A, load to be independent of APOE genotype. Cases with severe CAA had a lower parenchymal A, load than had those with moderate CAA (P = 0.003). Neither the severity of CAA nor the parenchymal A, load correlated with age of onset, duration of disease or age at death, and the severity of CAA also did not correlate with the presence of cerebral infarcts or foci of haemorrhage. These findings indicate that possession of the APOE,4 allele favours vascular over parenchymal accumulation of A, in AD. This may influence the pathogenesis of neurodegeneration in ,4-associated AD. [source] Linkage and Association Study of Late-Onset Alzheimer Disease Families Linked to 9p21.3ANNALS OF HUMAN GENETICS, Issue 6 2008S. Züchner Summary A chromosomal locus for late-onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy-confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli-Arab community. In the present study we analyzed an expanded clinical sample of 674 late-onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy-confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy-confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re-sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non-synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family-based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p. [source] Olfactory epithelium amyloid-, and paired helical filament-tau pathology in Alzheimer diseaseANNALS OF NEUROLOGY, Issue 4 2010Steven E. Arnold MD Objective Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, ,-synuclein, and amyloid-, lesions occur early and severely in cerebral regions of the olfactory system, and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, and disease specificity, and the relationships of OE pathology to brain pathology have not been established. Methods We investigated the pathological expression of amyloid-,, PHFtau, ,-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. Results Amyloid-, was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. ,-Synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-, and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical A, and PHFtau lesion ratings in the brain. Interpretation These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-, and PHFtau measurement in OE as a biomarker for AD. ANN NEUROL 2010;67:462,469 [source] Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects,ANNALS OF NEUROLOGY, Issue 4 2009Leslie M. Shaw PhD Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-, 1 to 42 peptide (A,1,42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and A,1,42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF A,1,42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for A,1,42, t-tau, and APO,4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/A,1,42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by A,1,42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. Ann Neurol 2009 [source] Phosphorylated Map Kinase (ERK1, ERK2) Expression is Associated with Early Tau Deposition in Neurones and Glial Cells, but not with Increased Nuclear DNA Vulnerability and Cell Death, in Alzheimer Disease, Pick's Disease, Progressive Supranuclear Palsy and Corticobasal DegenerationBRAIN PATHOLOGY, Issue 2 2001I. Ferrer Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in tau pathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau -positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD. [source] Cholesterol at the crossroads: Alzheimer's disease and lipid metabolismCLINICAL GENETICS, Issue 1 2004CL Wellington Alzheimer's Disease (AD) is a devastating disease that affects millions of elderly persons. Despite years of intense investigations, genetic risk factors that affect the majority of AD cases have yet to be determined. Recent studies suggest that cholesterol metabolism has integral part in AD pathogenesis, suggesting that genes that regulate lipid metabolism may also play roles in AD. This review will first describe emerging evidence that links cholesterol to the mechanisms thought to underlie AD. Based on this rationale, candidate genes located in regions implicated in AD that have roles in lipid metabolism will then be discussed. [source] | |||||||||||||