senility, a question.

CRP Is Linked to Inflammation and Thinking Problems
Fri, May 28, 2010 10:35:00 AM EST

A blood protein commonly associated with heart disease and inflammation is also linked to problems with thinking, a new study found. The findings further strengthen the growing links between heart health and brain health and point to a possible role of inflammation in contributing to the thinking problems of Alzheimer’s disease.

The protein, called C-reactive protein, or CRP, often signals that there is inflammation somewhere in the body when CRP levels are higher than normal. The more CRP a person has, the greater the likelihood of heart and blood vessel disease, heart attacks and strokes. These diseases are believed to involve inflammation within artery walls. Other studies have also linked high inflammation to an increased risk of Alzheimer’s and other forms of dementia, though the relationship still needs to be made clearer.

The new study was published in the journal Neurology, from the American Academy of Neurology. Researchers in Germany found that those with high CRP levels had brain changes associated with problems in so-called executive function, or the ability of the brain to plan and execute tasks and behave in an appropriate manner.

High levels of CRP, however, were not associated with problems in memory or language skills, which are often a prominent feature of Alzheimer’s disease. CRP did seem to correlate with defects in the brains frontal lobes, which are involved in thinking.

For the study, scientists examined 447 men and women, average age 63, who were mentally intact and free of symptoms of Alzheimer’s. They underwent a type of brain scan known as DTI, for diffusion tensor imaging, to look for defects in the brain’s white matter. They also completed tests to measure verbal recall and memory (the ability to use words) and executive function (planning and making decisions).

The study found that people with higher levels of CRP did worse on executive function tests. Overall, the average time to complete a test of executive function was 85 seconds. Those with the highest levels of CRP took an average of seven seconds longer to complete the test than those with the lowest levels of the protein. The brain changes measured with DTI were equivalent to 12 years of aging for those with the highest levels of CRP compared to those with the lowest levels.

More research is required to determine how inflammation may damage the brain and possibly contribute to Alzheimer’s disease. High levels of inflammation are known to damage blood vessels, including those in the brain. But even when the brain shows signs of damage, it does not mean someone will exhibit memory loss and other thinking problems related to Alzheimer’s.

“The use of aspirin and statin drugs as well as physical activity and controlling weight can help lower CRP levels in the body, but our analyses did not consider whether therapy would be effective or not,” said study author Dr. Heike Wersching of the University of Münster in Germany.

Continuing research into inflammation, the brain and Alzheimer’s will, however, help us understand the underlying mechanisms of the disease and may one day help lead to effective treatments.

By www.ALZinfo.org, The Alzheimer's Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer's Research Foundation at The Rockefeller University.

Source:
H. Wersching, MD; T. Duning, MD; H. Lohmann, PhD et al: Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function. Neurology, Vol. 74, March 30, 2010, pages 1022-1029.

http://www.alzinfo.org/newsarticle/templates/newstemplate.asp?articleid=406&zoneid=10

Decreased C-Reactive Protein Levels in Alzheimer Disease
Sid E. O'Bryant, PhD et al

Abstract
C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 ± 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 ± 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 µg/mL) versus controls (4.9 µg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

http://jgp.sagepub.com/content/23/1/49.abstract

I am guessing that in a small survey, all the dementia patients had way high CRP.
That still interests me. I share doubt re the process, but remain interested.

The mission of the Alzheimer's Disease Neuroimaging Initiative is developing biomarkers of Alzheimer's Disease in elderly subjects. A major goal of the study has been to establish and validate MRI and PET images, cerebral spinal fluid and blood biomarkers as predictors of the disease. Data collected throughout this study are available to the research community.

==============================================
STUDY OBJECTIVES (cfr. Protocol)
· To qualify the INNO-BIA plasma Aß forms assay for quantification of Aß1-42 and Aß1-40 in plasma samples from the ADNI study.
· To identify sources of variation between and within centers with respect to testing
of Aß isoforms in EDTA-plasma samples.
· To provide a template for validation of new plasma assays and/or biomarkers for use in the Biomarker Core of the US-ADNI.

1.4. STUDY APPROACH
Improvements in early detection and differential diagnosis of more common dementias such as Alzheimer’s disease (AD) and the search for disease progression markers are critically needed, along with effective disease-modifying treatments.

To this end, robust and validated detection of biomarkers is considered to be an essential means to improve diagnosis and to accelerate the development of new therapies [Shaw et al 2007]. Given that the accumulation of Aß peptides into senile plaques in the brain is one of the principal hallmarks of AD (Figure Intro-1), it is evident that the study of Aß isoforms in plasma represents a potentially rich line of investigation into the disease [Blennow et al. 2009; Golde et al. 2000; Graff-Radford et al. 2007; Lambert et al. 2009, Piccini et al. 2005; Schupf et al. 2008; Van Oijen et al. 2006].

The need to simultaneously investigate more than one form of ß-amyloid protein is based on findings that the deposition and resulting composition of neurotoxic Aß peptides is not uniform. When examining the brains of AD patients at autopsy, Aß peptide can be found as mixtures of full-length Aß1-40 and Aß1-42, as well as their C- or N-terminally modified forms (AßN-42 and AßN-40). These biomarkers have been found to be present in the earliest stages of AD [Sergeant et al 2003]. In cerebrospinal fluid (CSF), the ratio of full length Aß1-42/amino-modified Aß1-42 is able to predict more efficiently the conversion of mild cognitive impaired patients (MCI) to AD as compared to ß-amyloid1-42 alone [Vanderstichele et al. 2005].

http://www.adni-info.org/Scientists/Pdfs/Statistical_report_RRplasma_20032010_FINAL.pdf

whether or not the inflammation can be decreased by various means (pharmaceuticals, life style change, and so on).