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This Month in Archives of Neurology |

This Month in Archives of Neurology FREE

Arch Neurol. 2012;69(5):561-562. doi:10.1001/archneurol.2011.1454.
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CONTRIBUTIONS OF THE FRAMINGHAM HEART STUDY TO STROKE AND DEMENTIA EPIDEMIOLOGIC RESEARCH AT 60 YEARS

WolfArticle presents data from the Framingham Heart Study, the longest-running prospective epidemiologic study in history, which was initiated in 1948 in response to the rising toll of coronary heart disease and hypertension. During the ensuing decades, the study of other diseases, notably stroke and dementia, was added. Clinical correlation with systematic neuropathological examinations of more than 150 brains has provided important confirmation of cerebrovascular and brain tissue indices of disease. Identification of persons at heightened risk for stroke, mild cognitive impairment, Alzheimer disease, and cognitive decline years prior to disease onset may facilitate delay in disease onset and prevention.

BRAIN-IMMUNE INTERACTIONS AND ISCHEMIC STROKE: CLINICAL IMPLICATIONS

Kamel and IadecolaArticle review evidence showing that the central nervous system (CNS) and the immune system interact in complex ways and that better insight into these interactions may be relevant to the treatment of patients with stroke and other forms of CNS injury. Atherosclerosis, autoimmune disease, and physiological stressors such as infection or surgery cause inflammation that contributes to vascular injury and increases the risk of stroke. Further research will be required to determine what role, if any, immunity has in long-term outcomes after stroke, but elucidation of potential mechanisms may open promising avenues for the development of new therapeutics to improve neurological recovery after brain injury.

BIOMARKERS FOR INSULIN RESISTANCE AND INFLAMMATION AND THE RISK FOR ALL-CAUSE DEMENTIA AND ALZHEIMER DISEASE: RESULTS FROM THE FRAMINGHAM HEART STUDY

Van Himbergen and colleaguesArticle investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 levels) to the risk of developing Alzheimer disease (AD) and all-cause dementia. They report that, in women, increased plasma adiponectin levels are an independent risk factor for the development for both all-cause dementia and AD.

AUTOIMMUNE EPILEPSY: CLINICAL CHARACTERISTICS AND RESPONSE TO IMMUNOTHERAPY

Quek and colleaguesArticle describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy. When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome. Editorial perspective is provided by Gregory K. Bergey, MDArticle.

PREDICTORS OF SURVIVAL IN PATIENTS WITH PARKINSON DISEASE

Willis et alArticle determine the life expectancy of patients with Parkinson disease (PD) in the United States and identify demographic, geographic, and clinical factors that influence survival. They find demographic and clinical factors impact PD survival. Dementia is highly prevalent in patients with PD and is associated with a significant increase in mortality. They point out that more research is needed to understand whether environmental exposures influence PD course or survival.

SYNCOPE AND RAYNAUD'S DISEASE

Guiloff and colleaguesArticle investigate an association between syncope and Raynaud's disease (RD), its clinical features, and the effect of treatment with nifedipine. The association of syncope to RD was unrelated to chance or migraine. The temporal relation between syncope and Raynaud's phenomenon but not headache was statistically significant. Treatment with nifedipine stopped recurrent syncope in all patients.

COMPARISON OF IMAGING BIOMARKERS IN THE ALZHEIMER DISEASE NEUROIMAGING INITIATIVE AND THE MAYO CLINIC STUDY OF AGING

Whitwell et alArticle determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample. Rates of decline in hippocampal volume suggest that ADNI subjects have more aggressive brain pathology than MCSA subjects and hence may not be representative of the general population. These findings have implications for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages.

AUTOSOMAL DOMINANT FAMILIAL DYSKINESIA AND FACIAL MYOKYMIA: SINGLE EXOME SEQUENCING IDENTIFIES A MUTATION IN ADENYLYL CYCLASE 5

Chen et alArticle identify the gene responsible for familial dyskinesia and facial myokymia (FDFM) by exome resequencing of a single affected individual. They report that ADCY5 is highly expressed in striatum. Mice deficient in Adcy5 develop a movement disorder that is worsened by stress. They conclude that FDFM likely results from a missense mutation in ADCY5. This study demonstrates the power of a single exome sequence combined with linkage information to identify causative genes for rare autosomal dominant mendelian diseases.

EXERCISE ENGAGEMENT AS A MODERATOR OF THE EFFECTS OF APOE GENOTYPE ON AMYLOID DEPOSITION

Head and colleaguesArticle examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults. Collectively, their results suggest that cognitively normal sedentary APOE ϵ4–positive individuals may be at augmented risk for cerebral amyloid deposition.

ASSOCIATION OF LIFETIME COGNITIVE ENGAGEMENT AND LOW Β-AMYLOID DEPOSITION

Landau and colleaguesArticle assess the association between lifestyle practices (cognitive and physical activity) and β-amyloid deposition, measured with positron emission tomography using carbon 11–labeled Pittsburgh Compound B ([11C]PiB), in healthy older individuals. Individuals with greater early- and middle-life cognitive activity had lower [11C]PiB uptake. The tendency to participate in cognitively stimulating activities is likely related to engagement in a variety of lifestyle practices that have been implicated in other studies showing reduced risk of Alzheimer disease (AD)–related pathology. They report a direct association between cognitive activity and [11C]PiB uptake, suggesting that lifestyle factors found in individuals with high cognitive engagement may prevent or slow deposition of β-amyloid, perhaps influencing the onset and progression of AD.

 Image not available.

Cognitively normal older individuals with the lowest cognitive activity have amyloid burden that resembles that of patients with Alzheimer disease (AD). A, Carbon 11–labeled Pittsburgh Compound B ([11C]PiB) indices, reflecting amyloid deposition, in 10 patients with AD and 11 young controls were compared with older controls, who were subdivided into tertiles based on past cognitive activity scores. Within older controls, the cognitive activity tertiles differed from one another (P = .001 by the Kruskal-Wallis test) such that the lowest tertile had higher [11C]PiB uptake than the middle tertile (P = .04 by the Mann-Whitney test) and the top tertile (P = .001 by the Mann-Whitney test). The middle and highest tertiles were marginally different (P = .06). Patients with AD had higher [11C]PiB levels compared with older controls overall (P < .001) and young controls (P < .001). Young controls had lower [11C]PiB levels than older controls overall (P = .04). B, Regions in which past cognitive activity is inversely associated with [11C]PiB (blue; P = .001, cluster size = 100 voxels; controlling for age, sex, and years of education) overlaid, for comparison, on the set of regions used to calculate the mean cortical [11C]PiB indices for each study participant (cyan), which are plotted in A and listed in Table 2.

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