Background and Purpose—One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. Methods—The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. Results—The results of these discussions are reported herein. Conclusions—The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress. (Stroke. 2006;37:2220-2241.)

http://www.365heart.com/meeting/naozuzhong/pdf/vci.pdf

National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards

Subjective memory complaints (SMCs) are common in older people and are often thought to indicate cognitive impairment. We reviewed research on the relationship between SMCs and (a) current cognitive function, (b) risk of future cognitive decline, and (c) depression and personality. SMCs were found to be inconsistently related to current cognitive impairment but were more strongly related to risk of future cognitive decline. However, SMCs were consistently related to depression and some personality traits, e.g. neuroticism. In conclusion, the determinants of SMCs are complex. The utility of SMCs in the diagnosis of pre-dementia states (e.g. mild cognitive impairment) is uncertain and requires further evaluation.

Subjective Memory Complaints and Cognitive Impairment in Older People

While dementia affects 6-10% of persons 65 years or older, industrialized countries have witnessed an alarming rise in obesity. However, obesity's influence on dementia remains poorly understood. The conducted a systematic review and meta-analysis. PUBMED search (1995-2007) resulted in 10 relevant prospective cohort studies of older adults (40-80 years at baseline) with end points being dementia and predictors including adiposity measures, such as body mass index (BMI) and waist circumference (WC). There was a significant U-shaped association between BMI and dementia (P= 0.034), with dementia risk increased for obesity and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for underweight, overweight and obesity compared with normal weight in relation to incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimer's disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31) and were stronger in studies with long follow-up (>10 years) and young baseline age (<60 years). Weight gain and high WC or skin-fold thickness increased risks of dementia in all included studies. The meta-analysis shows a moderate association between obesity and the risks for dementia and AD. Future studies are needed to understand optimal weight and biological mechanisms

/pdf/obesity-and-central-obesity-as-risk-factors-for-incident-1i4y5nvzew.pdf

Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta‐analysis

We examined the association of diverse measures of social engagement with level of function in multiple cognitive domains in 838 persons without dementia who had a mean age of 80.2 (SD = 7.5). Social network size, frequency of social activity, and level of perceived social support were assessed in linear regression models adjusted for age, sex, education, and other covariates. Social activity and social support were related to better cognitive function, whereas social network size was not strongly related to global cognition. The results confirm that higher level of social engagement in old age is associated with better cognitive function but the association varies across domains of social engagement.

/pdf/social-engagement-and-cognitive-function-in-old-age-1ud9sipxr3.pdf

Social Engagement and Cognitive Function in Old Age

Alzheimer disease, the two-hit hypothesis: an update.

The sequencing of the complete genome for many organisms, including man, has opened the door to the systematic understanding of how complex structures such as the brain integrate and function, not only in health but also in disease. This blueprint, however, means that the piecemeal analysis regimes of the past are being rapidly superseded by new methods that analyse not just tens of genes or proteins at any one time, but thousands, if not the entire repertoire of a cell population or tissue under investigation. Using the most appropriate method of analysis to maximise the available data therefore becomes vital if a complete picture is to be obtained of how a system or individual cell is affected by a treatment or disease. This review examines what methods are currently available for the large scale analysis of gene and protein expression, and what are their limitations.

https://jnnp.bmj.com/content/jnnp/75/4/529.full.pdf

Functional genomics and proteomics: application in neurosciences

Comparative proteomic methods are rapidly being applied to many different biological systems including complex tissues. One pitfall of these methods is that in some cases, such as oncology and neuroscience, tissue complexity requires isolation of specific cell types and sample is limited. Laser microdissection (LMD) is commonly used for obtaining such samples for proteomic studies. We have combined LMD with sensitive thiol-reactive saturation dye labelling of protein samples and 2-D DIGE to identify protein changes in a test system, the isolated CA1 pyramidal neurone layer of a transgenic (Tg) rat carrying a human amyloid precursor protein transgene. Saturation dye labelling proved to be extremely sensitive with a spot map of over 5,000 proteins being readily produced from 5 mug total protein, with over 100 proteins being significantly altered at p < 0.0005. Of the proteins identified, all showed coherent changes associated with transgene expression. It was, however, difficult to identify significantly different proteins using PMF and MALDI-TOF on gels containing less than 500 mug total protein. The use of saturation dye labelling of limiting samples will therefore require the use of highly sensitive MS techniques to identify the significantly altered proteins isolated using methods such as LMD.

Paul R. Orange

Papers

Functional genomics and proteomics: application in neurosciences

Comparative proteomic analysis using samples obtained with laser microdissection and saturation dye labelling.