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PubMed2006

Estimating correlation coefficient between two variables with repeated observations using mixed effects model.

We estimate the correlation coefficient between two variables with repeated observations on each variable, using linear mixed effects (LME) model. The solution to this problem has been studied by many authors. Bland and Altman (1995) considered the problem in many ad hoc methods. Lam, Webb and O'Donnell (1999) solved the problem by considering different correlation structures on the repeated measures. They assumed that the repeated measures are linked over time but their method needs specialized software. However, they never addressed the question of how to choose the correlation structure on the repeated measures for a particular data set. Hamlett et al. (2003) generalized this model and used Proc Mixed of SAS to solve the problem. Unfortunately, their method also cannot implement the correlation structure on the repeated measures that is present in the data. We also assume that the repeated measures are linked over time and generalize all the previous models, and can account for the correlation structure on the repeated measures that is present in the data. We study how the correlation coefficient between the variables gets affected by incorrect assumption of the correlation structure on the repeated measures itself by using Proc Mixed of SAS, and describe how to select the correlation structure on the repeated measures. We also extend the model by including random intercept and random slope over time for each subject. Our model will also be useful when some of the repeated measures are missing at random.

Algorithms↗

PubMed2002

Intrafamilial correlation of clinical manifestations in neurofibromatosis 2 (NF2).

Measuring correlation in clinical traits among relatives is important to our understanding of the causes of variable expressivity in Mendelian diseases. Random effects models are widely used to estimate intrafamilial correlations, but such models have limitations. We incorporated survival techniques into a random effects model so that it can be used to estimate intrafamilial correlations in continuous variables with right censoring, such as age at onset. We also describe a negative-binomial gamma mixture model to determine intrafamilial correlations of discrete (e.g., count) data. We demonstrate the utility of these methods by analyzing intrafamilial correlations among patients with neurofibromatosis 2 (NF2), an autosomal-dominant disease caused by mutations of the NF2 tumor-suppressor gene. We estimated intrafamilial correlations in age at first symptom of NF2, age at onset of hearing loss, and number of intracranial meningiomas in 390 NF2 nonprobands from 153 unrelated families. A significant intrafamilial correlation was observed for each of the three features: age at onset (0.35; 95% confidence interval (CI) 0.23-0.47), age at onset of hearing loss (0.51; 95% CI, 0.35-0.64), and number of meninginomas (0.29; 95% CI, 0.15-0.43). Significant correlations were also observed for age at first symptom within NF2 families with truncating mutations (0.41; 95% CI, 0.06-0.68) or splice-site mutations (0.29; 95% CI, 0.03-0.51), for age at onset of hearing loss within families with missense mutations (0.67; 95% CI, 0.18-0.89), and for number of meningiomas within families with splice-site mutations (0.39; 95% CI, 0.13-0.66). Our findings are consistent with effects of both allelic and nonallelic familial factors on the clinical variability of NF2.

Adolescent↗

PubMed2005

The correlation between blood oxygenation level-dependent signal strength and latency.

PURPOSE: To investigate the relationship between signal strength and latency of the blood oxygenation level-dependent (BOLD) signal. MATERIALS AND METHODS: Several correlation analyses were performed on data obtained in a functional magnetic resonance imaging (fMRI) experiment, where subjects were presented with a simple visual stimulus. The BOLD signal strength was correlated with both the phase shift of the spectral density matrix and time-to-peak calculated from trial-averaged time courses. Correlation coefficients were calculated for visual stimuli of 2, 6, and 15 seconds in duration. RESULTS: Analyzing all functional runs for the same subject separately, i.e., including for each run all significantly activated voxels, we observed that correlations between phase shift and signal strength, as well as between time-to-peak and signal strength, decreased with increasing stimulus length. However, when analyses were restricted to voxels found activated in all functional runs, we observed similar correlations between BOLD signal strength and latency in all runs, independent of the length of stimulation. This result was again obtained for both latency measures: the spectral density phase shift and time-to-peak. CONCLUSION: For both latency measures, phase shift and time-to-peak, a high correlation between BOLD signal strength and latency was observed. We have shown that this correlation is independent of the length of visual stimulation. Thus, the correlation between BOLD signal strength and latency seems to be an inherent property of the BOLD response that is independent of the length of stimulation and can be observed using different methods for determining signal latency.

Adult↗

PubMed2006

Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura.

While autoimmune thrombocytopenic purpura is mediated by autoantibodies, accumulating evidence suggests that T helper cells and the cytokines they produce also play a key role. We determined correlations among age, serum cytokine concentrations, circulating lymphocyte, and platelet counts in adult (n=19) and children (n=29) with autoimmune thrombocytopenic purpura. Correlations between age and cytokine levels were also assessed in healthy controls (n=50). Significant positive correlations between age and serum levels of interferon-gamma, age and CD4+ lymphocytes, age and natural killer cell count were observed in these patients. Absolute lymphocyte and CD8+ cell count was significantly inversely correlated with age. In adult patients, a significant inverse correlation between platelet and absolute lymphocyte count was observed. In pediatric patients, an inverse correlation of platelet count with serum concentration of interleukin-3 was recorded. In 50 healthy volunteers there were significant positive correlations between age and interleukin-3, -4, -6, and interferon-gamma, and significantly negative correlations with interleukin-2, tumor necrosis factor-alpha, and interferon-alpha. Additional evaluations are necessary to identify the impact of age-related changes in immune function on the clinical course of autoimmune thrombocytopenic purpura.

Adolescent↗

PubMed1992

Correlation functions as a tool for protein modeling and structure analysis.

Proteins present unique folding structures whose conformations are determined primarily by their amino acid sequences. At present, there is no algorithm that would correlate the sequences with the structures determined by X-ray analysis or NMR. Comparative modeling of a new protein sequence based on the known structure of a functionally related protein promises to yield model structures that may provide relevant properties of the protein. To analyze the quality of a model structure, a set of correlation functions was derived from calculations on a subset of proteins from the structure database. Twenty-three highly resolved protein structures with resolutions of at least 1.7 A from various protein families were used as the primary database. The purpose of this initial work was to find highly sensitive functions (including statistical error limits for the parameters) that describe properties of "real" proteins. Each correlation described is characterized by the correlation coefficient, the parameters for linear or nonlinear regression (coefficients of the equation), standard deviation and variance, and the confidence limits describing the statistical probability for values to occur within these limits, e.g., the natural variability of the property under examination. In addition, a method was developed for creating reasonably misfolded proteins. The ability of a correlation function to discriminate between the native structure and the misfolded conformations is expressed by the reliability index, which indicates the sensitivity of a correlation function. The term correlation functions thus summarizes a variety of efforts to find a mathematical description for the properties of protein structures, for their correlation, and for their significance.

Computer Simulation↗

PubMed2006

Correlated mutations: advances and limitations. A study on fusion proteins and on the Cohesin-Dockerin families.

Correlated mutations have been repeatedly exploited for intramolecular contact map prediction. Over the last decade these efforts yielded several methods for measuring correlated mutations. Nevertheless, the application of correlated mutations for the prediction of intermolecular interactions has not yet been explored. This gap is due to several obstacles, such as 3D complexes availability, paralog discrimination, and the availability of sequence pairs that are required for inter- but not intramolecular analyses. Here we selected for analysis fusion protein families that bypass some of these obstacles. We find that several correlated mutation measurements yield reasonable accuracy for intramolecular contact map prediction on the fusion dataset. However, the accuracy level drops sharply in intermolecular contacts prediction. This drop in accuracy does not occur always. In the Cohesin-Dockerin family, reasonable accuracy is achieved in the prediction of both intra- and intermolecular contacts. The Cohesin-Dockerin family is well suited for correlated mutation analysis. Because, however, this family constitutes a special case (it has radical mutations, has domain repeats, within each species each Dockerin domain interacts with each Cohesin domain, see below), the successful prediction in this family does not point to a general potential in using correlated mutations for predicting intermolecular contacts. Overall, the results of our study indicate that current methodologies of correlated mutations analysis are not suitable for large-scale intermolecular contact prediction, and thus cannot assist in docking. With current measurements, sequence availability, sequence annotations, and underdeveloped sequence pairing methods, correlated mutations can yield reasonable accuracy only for a handful of families.

Amino Acids↗

PubMed2006

Structured correlation in models for clustered data.

Correlation is always a concern in the analysis of clustered data. One area of interest is to develop a general correlation modelling approach for high dimensional data with unbalanced hierarchical and heterogeneous data structures, e.g. multilevel data. Commonly used correlation structures might have limitation for such situations. In this paper, we propose two extensions, multiblock and multilayer correlations. These methods are very flexible in modelling correlation and can be incorporated in many multivariate approaches, while the major discussion focuses on the applications under the generalized estimating equations (GEE) methods. The approaches are especially useful in GEE when each cluster is large and complex but the number of clusters is small. If an incorrect correlation is applied to such data, the results are less efficient. Multiblock and multilayer correlations extend GEE methods to model complicated multilevel data with arbitrary number of levels and cluster size. The extended estimating equation for correlation parameters has an orthogonal property, and the computation is very efficient. A simulation study compares the conventional methods versus the proposed methods, and it shows the gain in relative efficiency and the flexibility in modelling various structures.

Adult↗

PubMed1992

Childhood blood pressure tracking correlations corrected for within-person variability.

The correlation coefficient between initial and subsequent blood pressure (BP) measurements is referred to as the tracking correlation. Childhood BP tracking correlations, although positive, have been considered too low to make accurate predictions for an individual. These correlations, however, can be raised substantially by averaging BP over multiple weekly visits in each year, which partially accounts for within-person variability. In a cohort of 333 school children, we measured BP 3 times on each of 4 successive weekly visits, in each of 4 consecutive years, using a random-zero sphygmomanometer. Approximately 90 per cent of subjects had data for one or more follow-up years, and 75 per cent of subjects who entered in the first year had data for all four years. With a model that allows estimation of correlations and that uses all available longitudinal data, we calculated tracking correlations completely corrected for within-person variability, the statistical equivalent of measuring BP on an infinite number (infinity) of visits and measurements per visit. Age-sex adjusted tracking correlations for 3 years of follow-up based on the means from 1,2,3,4, and infinity visits are, for systolic BP, 0.43, 0.56, 0.62, 0.66, and 0.73, respectively, and for diastolic BP, 0.20, 0.37, 0.46, 0.50, and 0.70, respectively. With longer follow-up, the use of corrected tracking correlations would allow determination of the maximal extent to which childhood BP can predict adult levels, and therefore the usefulness of screening to identify children at high risk of developing hypertension.

Adolescent↗

PubMed1997

Analysis of spin diffusion and cross correlation on the net nuclear Overhauser effect in NMR.

The effect of dipole-dipole cross correlations on the net nuclear Overhauser effect (NOE) has been analyzed here for realistic systems by extending the three-spin calculations to four and five spins in order to account for additional cross correlations and spin diffusion. These have been compared with the addition of leakage terms to the three-spin system. The additional spins enhance cross-correlation effects on one hand but on the other act as supplementary relaxation pathways for the magnetization to diffuse. This analysis shows that for a linear array of spins in the long-correlation limit, dipole-dipole cross correlations increase net NOE, while spin diffusion decreases it, and that the cumulative effect is a reduced effect of cross correlations. In other geometries and correlation limits, the effect of cross correlations on net NOE is generally small.

Magnetic Resonance Spectroscopy↗

PubMed1994

Rectification of correlation by a sigmoid nonlinearity.

We investigated the normalized autocovariance (correlation coefficient) function of the output of an erf() function nonlinearity subject to non-zero mean Gaussian noise input. When the sigmoid is wide compared to the input, or the input mean is close to the midpoint of the sigmoid, the output correlation coefficient function is very close to the input correlation coefficient function. When the noise mean and variance are such that there is a significant probability of operating in the saturation region and the sigmoid is not too flat, the correlation coefficient of the output function is less than that of the input. This difference is much greater when the correlation coefficient is negative than when it is positive. The sigmoid partially rectifies the correlation coefficient function. The analysis does not depend on the spectral properties of the input noise. All that is required is that the input at times t and (t + tau) be jointly gaussian with the same mean and autocovariance. The analysis therefore applies equally well to the case of two identical sigmoids with jointly gaussian inputs. This correlational rectification could help explain the parameter sensitivity of "neural network" models. If biological neurons share this property it could explain why few negative correlations between spike trains have been observed.

Animals↗

PubMed1992

Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer.

Placental isoferritin (PLF), an acidic isoform of ferritin, and its unique superheavy chain p43 have been recently described to be synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue, degree of differentiation, and prognosis, we have tried to evaluate the correlation of p43 in the cytosol of 122 breast cancer samples with commonly applied prognostic factors and features of proliferation and differentiation. In parallel, we investigated the correlation of p43 expression in MCF-7 and T47-D breast cancer cell lines during proliferation induced by estradiol plus fetal calf serum (assessed by 3H-thymidine incorporation), compared to p43 expression in stationary non-stimulated cell cultures. The levels of p43 in breast cancer cytosols correlated significantly negatively with tumor size (p = 0.0001), histologic grading (p = 0.0038), nuclear pleomorphism (p = 0.0019), rate of mitosis (p = 0.0002), and lymphocytic reaction (p = 0.0001), and significantly directly with the estrogen receptor status (p = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multivariate Cox model. In accordance with the observed negative correlation of features of differentiation vs. p43 expression, induction of proliferation by estradiol plus FCS added to serum-free tissue culture medium correlated with a decrease of p43 synthesis in both cell lines. Expression of p43 in estrogen and FCS-absent media revealed also a decrease in relation to a low spontaneous proliferation. However, the drop of p43 synthesis was significantly stronger in cell lines with estrogen-stimulated proliferation. Our in vitro and cytosol results confirm recent clinical observations describing an inverse correlation of p43 synthesis with the degree of proliferation and differentiation in breast cancer. However, the pathologic mechanisms leading to this phenomenon as well as the negative correlation with lymphocytic infiltration are still unclear and need to be further elucidated.

Breast Neoplasms↗

PubMed1996

Lack of correlation of anorectal manometry with symptoms of chronic childhood constipation and encopresis.

UNLABELLED: Chronic constipation is an extremely common problem in children. Many authors have advocated using anorectal manometric examination during evaluation of chronic childhood constipation and encopresis as a means of developing individualized modes of treatment. PURPOSE: This study was designed to prospectively examine frequency and severity of symptoms of childhood constipation and encopresis and associate these symptoms with anorectal manometric findings. METHODS: Forty-four children with chronic constipation participated in the study. Before performing anorectal manometry, bowel-related symptoms were collected for two consecutive weeks with a computerized voice mail system. Anorectal manometry was performed using a triple lumen catheter attached to a hydraulic manometry infusion system. RESULTS: Frequency of voluntary bowel movements did not correlate with any manometric parameters. Frequency of fecal soiling, age at onset of symptoms, and duration of symptoms were all highly correlated with degree of sphincter spasm during attempted defecation; however, none of these variables correlated with any other manometric parameter. Amount of pain associated with bowel movements correlated with frequency of soiling and was inversely correlated with maximum squeeze pressure but was not correlated with any other manometric parameter. CONCLUSIONS: In children with chronic constipation and encopresis, sphincter spasm demonstrated with anorectal manometry is highly correlated with frequency of fecal soiling, age at onset, and duration of symptoms; however, none of the other commonly measured manometric parameters appear to correlate with symptoms of chronic childhood constipation and encopresis.

Age of Onset↗

PubMed2005

Right-left correlation of the sympathetically induced fluctuations of photoplethysmographic signal in diabetic and non-diabetic subjects.

Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood volume by light-transmission measurements. The baseline and amplitude of the PPG signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated by the sympathetic nervous system, and high correlation between right and left extremities of healthy subjects. As sympathetic neuropathy is one of the diabetic complications, the right-left correlation of the PPG fluctuations was examined in diabetic patients. The PPG signal was simultaneously measured in the two index fingers and the two second toes of 35 diabetic patients and 33 non-diabetic subjects. For each PPG pulse, the baseline and amplitude were determined, and the right-left correlation coefficients of the VLF fluctuations in the baseline and amplitude were derived. The VLF fluctuations in the baseline showed high right-left correlation, both for fingers (0.93 +/- 0.05) and toes (0.93 +/- 0.06), for the non-diabetic subjects, and significantly lower correlation (0.78 +/- 0.22 and 0.84 +/- 0.17, respectively) for the diabetic patients. Similar results were obtained for the amplitude VLF fluctuations. The right-left correlation coefficients for diabetic patients decreased with the disease duration for the toe baseline and toe amplitude fluctuations and correlated with heart rate response to deep breathing for the finger baseline and toe amplitude fluctuations. The right-left correlation coefficients of the PPG fluctuations provide a simple and convenient means for assessing the adequacy of the sympathetic nervous system function.

Adult↗

PubMed1999

Level of use of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with EEG power and coherence.

RATIONALE: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. OBJECTIVE: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. METHODS: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject's consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. RESULTS: MDMA use was positively correlated with absolute power in the alpha (8-12 Hz) and beta (12-20 Hz) frequency bands, but not with the delta (1-3 Hz) or theta (4-7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. CONCLUSIONS: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs.

Adolescent↗

PubMed2003

Statistical analysis of the impact of spectral correlation on observed formation constants from UV-visible spectroscopic measurements.

Information retrieved from UV-visible spectroscopic data by application of a self-modelling factor analysis algorithm showed apparently systematically shifted thermodynamic properties for the same chemical system as a function of spectral slit widths. This empirical observation triggered a systematic investigation into the likely effects of residual and spectral correlation on the numerical results from quantitative spectroscopic investigations. If slit width was a nuisance factor it would reduce the comparability of information evaluated from spectroscopic data. The influence of spectral slit width was investigated by simulation, i.e. by generating and evaluating synthetic spectra with known properties. The simulations showed that increasing spectral correlation may introduce bias into factor analysis evaluations. By evaluation of the complete measurement uncertainty budget using threshold bootstrap target factor (TB CAT) analysis, the apparent shifts are insignificant relative to the total width of the quantity's measurement uncertainty. Increasing the slit widths causes some systematic effects, for example broadening of the registered spectral bands and reduction of spectral noise, because of higher light intensity passing to the detector. Hence, the observed systematic shifts in mean values might be caused by some latent correlation. As a general conclusion, slit width does not affect bias. However, the simulations show that spectral correlation and residual correlation may cause bias. Residual correlation can be taken into account by computer-intensive statistical methods, for example moving block or threshold bootstrap analysis. Spectral correlation is a property of the chemical system under study and cannot be manipulated. As a major result, evidence is given showing that stronger spectral correlation ( r<-0.7) causes non-negligible bias in the evaluated thermodynamic information from such a system.

Journal Article↗

PubMed1996

Clinical trials: relevance of correlation between treatment responses.

OBJECTIVE: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities. METHODS: Using a hypothetical example and several published studies we examine the influence of correlation levels between treatment modalities on the sensitivity of testing. RESULTS: The level of correlation between responses to different treatment modalities is a major determinant of the sensitivity both of crossover and parallel group clinical trials. CONCLUSIONS: It is very relevant to assess a priori correlation levels between responses to the different treatment modalities of a trial. If a negative correlation is anticipated, a crossover design is likely to lack sensitivity. If a positive correlation is anticipated a parallel-group design seems less appropriate, because it would lack the extra sensitivity of accounting for the positive correlation. Both designs would seem suitable for approximately zero correlations (e.g. comparison vs baseline or vs placebo under the assumption that the number of placebo responders is negligible.

Clinical Trials as Topic↗

PubMed2005

Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)]]. The daily glucocorticoid dose was 10 mg prednisone equivalent (median), and the cumulative dose was 12 g prednisone equivalent (median). None of the patients had previously taken medication for osteoporosis. Osteoporosis was demonstrated in 35.3% of the patients, osteopenia in 47.5%, and a normal BMD in 17.2%. The results of tandem-MP ostase correlated with the BMD of the lumbar spine and of the femoral neck. The values for N-terminal telopeptide and pyridinoline correlated only with the bone density of the femoral neck. All results were statistically significant, although the correlation coefficients were low. After classification of the patients according to their BMD values (osteoporosis, osteopenia and normal BMD), there were significantly more patients with bone markers above the norm in the osteoporosis group and in the osteopenia group than in the group with normal bone density. All bone markers recorded behaved similarly in relation to the bone density values. The same analysis was also undertaken for the different disease groups. In these subgroups there was also a correlation between ostase/crosslinks with BMD, but the correlation coefficients were low. A general recommendation for the routine use of a specific bone marker in patients with rheumatic diseases on glucocorticoid therapy cannot be made from a cost-benefit point of view mainly because of limited predictive power (low correlation coefficients, incomplete correlation with different sites of BMD measurement).

Adult↗

PubMed2003

Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology--a pilot study.

Data on the relationship between cerebral amyloid angiopathy (CAA) ("congophilic angiopathy") and Alzheimer's disease (AD) pathology are conflicting. In the present study, CAA and capillary CAA (CapCAA) ("dyshoric angiopathy") were examined in the frontal cortex of 100 human brains obtained at autopsy from both male and female, demented and non-demented patients (mean age +/- SD 84.3+/-9.3 years); 50 brains with high (mean 5.0) and 50 with low (mean 2.4) Braak stages. CAA was assessed according to the method of Olichney et al. [25]; CapCAA was grouped into four grades by counting the affected capillaries in 10 high power fields. General CAA was present in 61% (87.5% demented, 55.6% non-demented; 70% with high and 52% low Braak stages). CAA did not correlate with either clinical diagnosis of dementia or high-grade AD pathology; CapCAA showed a low correlation with dementia and a medium positive correlation with high Braak stages. The severity of both lesions did not correlate with clinical dementia; whereas that of CAA showed low correlation with CERAD, Braak, and NIA-Reagan-Institute criteria, the severity of CapCAA correlated significantly with all three AD criteria. The presence and severity of CAA and CapCAA showed only low correlation, suggesting a different pathogenesis of these types of lesion. Since CapCAA represents insoluble amyloid peptide (Abeta) deposits in and around capillaries, its correlation with neuritic AD pathology supports the concept of neuronal origin of Abeta via drainage from interstitial fluid from the central nervous system to capillary walls. Studies to answer the question whether CapCAA represents an epiphenomenon or an indicator of a pathogenic association between tau cytopathology and Abeta deposition in capillaries are in progress.

Aged↗