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PubMed1987

High resolution computed tomography of inflation-fixed lungs. Pathologic-radiologic correlation of centrilobular emphysema.

Centrilobular emphysema (CLE) is a disease defined pathologically. Assessment of the accuracy of high resolution computed tomography (CT) in the diagnosis of centrilobular emphysema has been hampered by a lack of pathologic correlation. We applied high resolution computed tomography to 20 postmortem lung specimens fixed by a method that allows for direct one-to-one pathologic-radiologic correlation. The degree of centrilobular emphysema was assessed radiologically on a visual grading system based on nonperipheral low-attenuation areas. The lungs were then sectioned along the plane of the CT image, and the degree of centrilobular emphysema was graded pathologically by scoring against a panel of standards. A significant correlation (r = 0.91, p less than 0.005) was found between the pathologic grade and the in vitro CT score.

Histological Techniques↗
PubMed1990

The diagnosis of mild emphysema. Correlation of computed tomography and pathology scores.

Early and accurate diagnosis of emphysema is said to be invaluable for identification of clinically silent and mild emphysema. Recently, computed tomography (CT) has been much advocated for its efficacy in detailed diagnosis of emphysema, and the results have been compared with the pathology grade of emphysema in resected lung specimens. To assess the ability of high resolution CT scan in detecting and grading mild emphysema, we correlated the high resolution CT scan with the pathology grade of emphysema and the destructive index (DI) of lung specimens from 42 patients undergoing thoracotomy for a solitary pulmonary nodule. The high resolution CT scan and the cut surface of the lung, corresponding exactly to the same plane of the CT scan image, were assessed using the picture-grading system of Thurlbeck and coworkers on a scale of zero to 100. The CT scores for all patients ranged from 12 to 57, with a mean +/- SD of 22.1 +/- 9.6 using 1-mm collimation (n = 35), and from 7 to 46 with a mean +/- SD of 16.5 +/- 8.3 using 5-mm collimation (n = 33). The pathology scores ranged from 10 to 57, with a mean +/- SD of 23.2 +/- 9.8 (n = 42). The DI ranged from 15.4 to 67.1, with a mean +/- SD of 31.4 +/- 10.8 (n = 42). The CT scores using 1-mm and 5-mm collimation correlated significantly with the pathology scores (r = 0.68 and 0.76, respectively, p less than 0.001), and with the DI (r = 0.62 and 0.74, respectively, p less than 0.001). The pathology scores correlated significantly with the DI (r = 0.72, p less than 0.001). We therefore concluded that high resolution CT can help to identify the presence and grading of mild emphysema.

Adult↗
PubMed1976

Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome.

In 45 consecutive patients referred for severe hypoxemia (Pao2 less than 100 mm Hg on positive end-expiratory pressure of 5 cm H2O and fraction of inspired O2 of 1.0), physiologic studies of gas exchange were correlated with pathologic features from 36 open lung biopsies and 15 autopsies. Three distinct groups were defined. Group 1 included 11 patients with the most severe hypoxia (Pao2, 47 +/- 12 mm Hg), minimal Pao2 response to a 10 cm H2O increase in positive end-expiratory pressure (+2.0 +/- 4.0 mm Hg), and a fixed shunt at all fractions of inspired O2. Pathologic study showed edema, exudation, and hemorrhage to the point of consolidation. In group 2 were 13 patients who had less severe hypoxia (Pao2, 60 +/- 17 mm Hg) and a moderate Pao2 response to a 10 cm H2O increase in positive end-expiratory pressure (+15 +/- 8 mm Hg), but whose maximal response was slowly achieved (30 min to several hours). Pathologic examination showed extensive fibrosis. The 21 patients in group 3 had the least hypoxia (66 +/- 15 mm Hg), and had a rapid and marked improvement in Pao2 with a 10 cm H2O increase in positive end-expiratory pressure (+68 +/- 59 mm Hg). Pathologic features were similar to but less severe than those in group 1. Venous admixture increased with decreasing inspired concentrations of O2, indicating diffusion or ventilation-perfusion abnormalities in groups 2 and 3. Prognosis was best for group 3, with 10 of 21 long-term survivors. Two of 11 group 1 patients survived, but only after prolonged periods of extracorporeal membrane oxygenation. Despite biopsy evidence of extensive fibrosis, 3 of 13 in group 2 survived with moderate to good pulmonary function, including 1 survivor who had had extracorporeal membrane oxygenation. Such combined physiologic and pathologic studies are useful (1) for optimal respiratory care, (2) for prognosis, (3) for development of indications for extracorporeal membrane oxygenation, and (4) for better understanding of the pathophysiology of adult respiratory distress syndrome.

Air Sacs↗
PubMed1999

Prevalence, assessment, and treatment of pathological gambling: a review.

OBJECTIVE: Although pathological gambling is an increasing problem, many mental health providers are unfamiliar with its diagnosis and treatment. To improve recognition and treatment of pathological gambling, the authors reviewed the literature on its prevalence, assessment, and treatment. METHODS: Entries in PsycLIT and MEDLINE were examined for the years 1984 to 1998. RESULTS AND DISCUSSION: The prevalence of pathological gambling seems to be increasing with the spread of legalized gambling; casinos are now operating in 27 states. Point and lifetime prevalence rates of pathological gambling are reported to be as high as 1.4 percent and 5.1 percent, respectively. The most commonly used assessment instrument is the DSM-based, 20-item South Oaks Gambling Screen. There is no standard treatment for pathological gambling. Gamblers Anonymous (GA) is the most popular intervention, and about 1,000 chapters exist in the U.S. Studies suggest that only 8 percent of GA attendees achieve a year of abstinence. Combining professional therapy and GA participation may improve retention and abstinence. Marital and family treatments, including participation in Gam-Anon, the spousal component of GA, have not been sufficiently evaluated. The few studies of cognitive-behavioral treatments suggest that this approach, which may include cognitive restructuring, problem solving, social skills training, and relapse prevention, is promising. Carbamazepine, naltrexone, clomipramine, fluvoxamine, and lithium have been used with some effect. Therapists' manuals and self-help manuals are available. Although research evaluating their efficacy is necessary, manuals can provide a start for therapists who encounter patients with gambling problems. Brief motivational interviewing may be a useful strategy for decreasing gambling among heavy gamblers who are ambivalent about entering treatment or who do not desire abstinence.

Cognitive Behavioral Therapy↗
PubMed2002

Analysis of spiral ganglion cell populations in children with normal and pathological ears.

This study analyzed features of total and segmental spiral ganglion cell populations in children with normal ears and those with various pathological conditions. Sixty-three human temporal bone specimens, obtained from 43 children 4 days to 9 years of age, were studied histopathologically. These specimens were divided into 5 diagnostic groups: group 1, normal ears (13 ears); group 2, congenital infectious diseases (13 ears); group 3, chromosomal aberrations (11 ears); group 4, multiple craniofacial anomalies with hereditary or genetic causes (21 ears); and group 5, perinatal and postnatal asphyxia (5 ears). Eighteen of the 63 ears had documented profound deafness. In either normal ears (group 1) or those with various pathological conditions (groups 2 through 5), the total number of ganglion cells did not change as a function of age during the first 10 years. The total number of ganglion cells was significantly larger in group 1 (33,702) than in each of groups 2, 3, 4, and 5 (p < .01), and the number was significantly larger in group 2 than in each of groups 4 and 5 (p < .01 and p < .05, respectively). The ratio of basal to apical ganglion cell populations remained constant in both normal and pathological ears. Each ratio of the number of basal and apical ganglion cells in groups 2, 3, 4, and 5 to the mean number in group 1 (basal and apical survival ratios) was at least approximately 40%. There was no statistical difference between these two ratios in groups 2, 3, 4, and 5. The mean (+/-SD) total number of ganglion cells in ears with documented profound deafness was 15,417 +/- 5,944, which is approximately 40% of those present in normal ears. Our results suggest that normally, cochlear neurons are completely present at birth and minimally regress during the first decade of life. In addition, although intergroup differences among various pathological groups were present, the majority of pathological ears had more than 10,000 spiral ganglion cells present. Cochlear implantation has gradually been recognized as an effective and reliable tool for rehabilitation of children who have profound deafness, even congenitally or prelingually deafened children. On the basis of the results obtained in this study, we discuss the implications for cochlear implantation in children.

Age Factors↗
PubMed2002

Improved detection of substantia nigra pathology in Alzheimer's disease.

The role of substantia nigra pathology in Alzheimer's disease (AD) is uncertain. Detection of pathology may be obscured by intraneuronal neuromelanin and influenced by stains. We determined methods for optimal visualization of nigral pathology in 45 cases of AD. For detection of Lewy bodies (LBs), we compared ubiquitin and alpha-synuclein immunostains to hematoxylin and eosin (H&E). For neurofibrillary tangles (NFTs) and neuropil threads (NTs), we compared Gallyas silver and paired helical filament (PHF) immunostains, after bleaching of melanin, to modified Bielschowsky, Gallyas, and PHF alone. The number of LB cases was not different using the three stains. However, more LBs per section were detected using alpha-synuclein (z=4.88, p<0.001). Twice the number of cases exhibited NFT (z=8.21; p<0.001) and the mean NFT number per section was 2.8-5.2-fold greater, using Gallyas and PHF after bleaching compared to without bleaching (chi(2)=142.17; p<0.001). More NTs (z=6.54; p<0.001) were observed with PHF and Gallyas after bleaching. With optimal methods, we found LBs in 27%, NFTs in 89%, and NTs in all 45 AD cases. We show that detection of nigra pathology is influenced by histological method. Clinicopathological studies using these methods are needed to determine the role of nigral pathology in AD.

Aged↗
PubMed2005

Prevalence of pathological gambling in Quebec in 2002.

OBJECTIVE: To assess gambling behaviours and the problems associated with pathological gambling among the adult population of Quebec in 2002. METHOD: In Phase 1 of this 2-phase study, a total sample of 8842 adults was assessed. We used the South Oaks Gambling Screen (SOGS), adapted for telephone interview, to assess one-half of the sample; the other one-half was evaluated with the Canadian Problem Gambling Index (CPGI). In the study's second phase, we compared the classifications obtained from these screening instruments with classifications obtained by a psychologist using a semistructured clinical telephone interview. RESULTS: The results indicate that the prevalence of pathological gambling in 2002 (at which time 0.8% of the adult population were classified as probable pathological gamblers) did not differ from the proportion obtained in 1996 (1.0%), despite the significant decrease in gambling participation in 2002 (81% vs 90% in 1996). The most popular gambling activities were buying lottery tickets (68%), participating in fundraising draws (40%), gambling in casinos (18%), playing cards with family or with friends (10%), playing bingo (9%), and playing video lotteries (8%). The findings obtained from the SOGS and the CPGI revealed that the 2 instruments perform similarly when identifying pathological gambling prevalence. However, the results of the semistructured clinical telephone interviews differed from the results obtained with the screening instruments: 82% of the gamblers initially identified as probable pathological gamblers by the SOGS or the CPGI were not confirmed by a clinical interview. CONCLUSION: The discrepancy between the results of the screening questionnaires and the clinical evaluation is significant, and this difference needs to be addressed before further cross-sectional or longitudinal studies are conducted.

Adult↗
PubMed2025

A computational ontology framework for the synthesis of multi-level pathology reports from brain MRI scans.

BackgroundConvolutional neural network (CNN) based volumetry of MRI data can help differentiate Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) as causes of cognitive decline and dementia. However, existing CNN-based MRI volumetry tools lack a structured hierarchical representation of brain anatomy, which would allow for aggregating regional pathological information and automated computational inference.ObjectiveDevelop a computational ontology pipeline for quantifying hierarchical pathological abnormalities and visualize summary charts for brain atrophy findings, aiding differential diagnosis.MethodsUsing FastSurfer, we segmented brain regions and measured volume and cortical thickness from MRI scans pooled across multiple cohorts (N&#x2009;=&#x2009;3433; ADNI, AIBL, DELCODE, DESCRIBE, EDSD, and NIFD), including healthy controls, prodromal and clinical AD cases, and bvFTD cases. Employing the Web Ontology Language (OWL), we built a semantic model encoding hierarchical anatomical information. Additionally, we created summary visualizations based on sunburst plots for visual inspection of the information stored in the ontology.ResultsOur computational framework dynamically estimated and aggregated regional pathological deviations across different levels of neuroanatomy abstraction. The disease similarity index derived from the volumetric and cortical thickness deviations achieved an AUC of 0.88 for separating AD and bvFTD, which was also reflected by distinct atrophy profile visualizations.ConclusionsThe proposed automated pipeline facilitates visual comparison of atrophy profiles across various disease types and stages. It provides a generalizable computational framework for summarizing pathologic findings, potentially enhancing the physicians' ability to evaluate brain pathologies robustly and interpretably.

Humans↗
PubMed2006

Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

BACKGROUND: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components. METHODS: Of 227 subfertile women, serum was available for C. trachomatis IgG antibody testing and genotyping (common versus rare allele) of the PRR genes TLR9, TLR4, CD14 and CARD15/NOD2. In all women, a laparoscopy was performed to assess the grade of tubal pathology. Tubal pathology was defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. RESULTS: Following a C. trachomatis infection (i.e. C. trachomatis IgG positive), subfertile women carrying two or more SNPs in C. trachomatis PRR genes were at increased risk of tubal pathology compared to women carrying less than two SNPs (73% vs 33% risk). The differences were not statistically significant (P = 0.15), but a trend was observed. CONCLUSION: Carrying multiple SNPs in C. trachomatis PRR genes tends to result in an aberrant immune response and a higher risk of tubal pathology following a C. trachomatis infection. Larger studies are needed to confirm our preliminary findings.

Antibodies, Bacterial↗
PubMed2006

Prognostic significance of pathological response after neoadjuvant chemotherapy or chemoradiation for locally advanced cervical carcinoma.

BACKGROUND: Cisplatin-based chemoradiation is the standard of care for locally advanced cervical cancer patients; however, neoadjuvant modalities are currently being tested. Neoadjuvant studies in several tumor types have underscored the prognostic significance of pathological response for survival; however there is a paucity of studies in cervical cancer investigating this issue. METHODS: Four cohorts of patients with locally advanced cervical carcinoma (stages IB2-IIIB); included prospectively in phase II protocols of either neoadjuvant chemotherapy with 1) cisplatin-gemcitabine, 2) oxaliplatin-gemcitabine, 3) carboplatin-paclitaxel or 4) chemoradiation with cisplatin or cisplatin-gemcitabine followed by radical hysterectomy were analyzed for pathological response and survival. RESULTS: One-hundred and fifty three (86%) of the 178 patients treated within these trials, underwent radical hysterectomy and were analyzed. Overall, the mean age was 44.7 and almost two-thirds were FIGO stage IIB. Pathological response rates were as follows: Complete (pCR) in 60 cases (39.2%), Near-complete (p-Near-CR) in 24 (15.6 %) and partial (pPR) in 69 cases (45.1%). A higher proportion rate of pCR was observed in patients treated with chemoradiotherapy (with cisplatin [19/40, 47.5%]; or with cisplatin-gemcitabine [24/41, 58.5%] compared with patients receiving only chemotherapy, 6/23 (26%), 3/8 (37.5%) and 8/41 (19.5%) for cisplatin-gemcitabine, oxaliplatin-gemcitabine and carboplatin-paclitaxel respectively [p = 0.0001]). A total of 29 relapses (18.9%) were documented. The pathological response was the only factor influencing on relapse, since only 4/60 (6.6%) patients with pCR relapsed, compared with 25/93 (26.8%) patients with viable tumor, either pNear-CR or pPR (p = 0.001). Overall survival was 98.3% in patients with pCR versus 83% for patients with either pNear-CR or pPR (p = 0.009). CONCLUSION: Complete pathological response but no Near-complete and partial responses is associated with longer survival in cervical cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy.

Journal Article↗
PubMed2004

Correlation between imaging and pathology in ductal carcinoma in situ of the breast.

BACKGROUND: It is helpful in planning treatment for patients with ductal carcinoma in situ (DCIS) if the size and grade could be reliably predicted from the mammography. The aims of this study were to determine if the type of calcification can be best used to predict histopathological grade from the mammograms, to examine the association of mammographic appearance of DCIS with grade and to assess the correlation between mammographic size and pathological size. METHODS: Mammographic films and pathological slides of 115 patients treated for DCIS between 1986 and 2000 were reviewed and reclassified by a single radiologist and a single pathologist respectively. Prediction models for the European Pathologist Working Group (EPWG) and Van Nuys classifications were generated by ordinal regression. The association between mammographic appearance and grade was tested with the chi2-test. Relation of mammographic size with pathological size was established using linear regression. The relation was expressed by the correlation coefficient (r). RESULTS: The EPWG classification was correctly predicted in 68%, and the Van Nuys classification in 70% if DCIS was presented as microcalcifications. High grade was associated with presence of linear calcifications (p < 0.001). Association between mammograhic- and pathological size was better for DCIS presented as microcalcifications (r = 0.89, p < 0.001) than for DCIS presented as a density (r = 0.77, p < 0.001). CONCLUSIONS: Prediction of histopathological grade of DCIS presenting as microcalcifications is comparable using the Van Nuys and EPWG classification. There is no strict association of mammographic appearance with histopathological grade. There is a better linear relation between mammographic- and pathological size of DCIS presented as microcalcifications than as a density, although both relations are statistically significant.

Journal Article↗
PubMed2006

CD40 deficiency mitigates Alzheimer's disease pathology in transgenic mouse models.

We have previously shown that transgenic mice carrying a mutant human APP but deficient in CD40L, display a decrease in astrocytosis and microgliosis associated with a lower amount of deposited Abeta. Furthermore, an anti-CD40L treatment causes a diminution of Abeta pathology in the brain and an improved performance in several cognitive tasks in the double transgenic PSAPP mouse model. Although these data suggest a potential role for CD40L in Alzheimer's disease pathology in transgenic mice they do not cast light on whether this effect is due to inhibition of signaling via CD40 or whether it is due to the mitigation of some other unknown role of CD40L. In the present report we have generated APP and PSAPP mouse models with a disrupted CD40 gene and compared the pathological features (such as amyloid burden, astrocytosis and microgliosis that are typical of Alzheimer's disease-like pathology in these transgenic mouse strains) with appropriate controls. We find that all these features are reduced in mouse models deficient for CD40 compared with their littermates where CD40 is present. These data suggest that CD40 signaling is required to allow the full repertoire of AD-like pathology in these mice and that inhibition of the CD40 signaling pathway is a potential therapeutic strategy in Alzheimer's disease.

Journal Article↗
PubMed2002

Preoperative combined nested reverse transcriptase polymerase chain reaction for prostate-specific antigen and prostate-specific membrane antigen does not correlate with pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy.

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy. PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure. RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P =.026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P =.009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P =.004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P =.009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results. CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.

Antigens, Surface↗
PubMed2005

Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma.

PURPOSE: To determine pathologic response rates to liposome-entrapped cis-bisneodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (L-NDDP) administered intrapleurally in patients with malignant pleural mesothelioma. PATIENTS AND METHODS: Thirty-three patients with malignant pleural mesothelioma and free-flowing pleural effusions received intrapleural L-NDDP once every 3 weeks at a dose of 450 mg/m2. Thoracoscopic evaluation with pleural biopsies was performed before therapy and then after every two cycles. The primary end point was pathologic response as determined by thoracoscopic biopsy. RESULTS: After at least two cycles, post-treatment pleural biopsy analysis was negative in 14 patients for a pathologic response rate of 42% (95% CI, 25% to 61%). Median survival was 11.2 months. There were three treatment-related deaths secondary to peritonitis, cellulitis at the thoracoscopy site, and empyema. Grade 3 nonhematologic toxicities included infection, fever, dyspnea, and anorexia, which occurred in five (15%), one (3%), one (3%), and one (3%) patients, respectively. There were no grade 4 nonhematologic toxicities. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in five (15%), three (9%), and two (6%) patients, respectively. Two patients with pathologic responses subsequently underwent pleural decortication. Both surgical specimens revealed residual tumor in regions that were not in direct communication with the pleural space. CONCLUSION: Intrapleural L-NDDP therapy in this patient population is feasible with significant but manageable toxicity. Although pathologic responses are highly encouraging, areas of mesothelioma that are not in direct communication with the pleural space will evade drug exposure and limit efficacy in some patients. The optimal role of intrapleural L-NDDP therapy currently remains to be determined.

Adult↗
PubMed1996

Projection on projective techniques = pathology: the problem that is not being addressed.

A replication of the "levels effect" and reported correlation of "projection" and "pathology" was undertaken using a selected set of Thematic Apperception Test (Murray, 1943) cards varied for ambiguity and scored for pathology and projection. The levels effect was not found for pathology in either a normal or psychiatric group, but was found for projection in the normal group. The correlation between projection and pathology was again clearly confirmed. It was concluded that failure to take into consideration the stimulus properties of the cards and the context in which the test was administered may lead to false attribution of pathology to normal test-takers.

Adolescent↗
PubMed2006

Diabetes is related to cerebral infarction but not to AD pathology in older persons.

OBJECTIVE: To examine the potential relation of diabetes to common neuropathologic causes of dementia, cerebral infarction and Alzheimer disease (AD) neuropathology. METHODS: Subjects were 233 older Catholic clergy in the Religious Orders Study, who underwent detailed annual evaluations, including neuropsychological testing, and brain autopsy at time of death (mean age 86 years, 45% men). Diabetes was identified by annual direct medication inspection and history. Cognitive function proximate to death was summarized into five cognitive domains, based on 19 neuropsychological tests. Macroscopic cerebral infarctions were recorded from 1 cm coronal slabs. Neuritic plaques, diffuse plaques, and neurofibrillary tangles were counted in Bielschowsky silver-stained sections and summarized to yield composite measures of neuritic plaques, diffuse plaques, tangles, and overall AD pathology. We also used immunohistochemistry with antibodies to amyloid-beta and PHF-tau to obtain quantitative measures of amyloid burden and neurofibrillary tangle density. Multiple logistic and linear regression analyses were used to examine the relation of diabetes to cerebral infarctions and AD pathology, controlling for age, sex, and education. RESULTS: AD pathology was related to all five cognitive domains (p < 0.01) and infarctions were related to perceptual speed (p < 0.001). Diabetes (present in 15% subjects) was associated with an increased odds of infarction (OR = 2.47, 95% CI: 1.16, 5.24). Diabetes was not related to global AD pathology score, or to specific measures of neuritic plaques, diffuse plaques or tangles, or to amyloid burden or tangle density. CONCLUSION: We found a relation between diabetes and cerebral infarction but not between diabetes and Alzheimer disease pathology in older persons.

Aged↗
PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗
PubMed1996

Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria.

Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.

Aged↗