O ur objective is to characterize the development of the literature on hypertension and cognitive functioning from a historical perspective. This goal was stimulated by the review on "Historical Trends and Milestones in Hypertension Research" in the October 2012 issue of Hypertension.1 Our specific aims are threefold: (1) to trace and describe the history of this area of research; (2) to identify milestones in knowledge and methods; and (3) to discuss briefly how this literature translates into patient care. The topic is of major relevance to research and practice because hypertension is a well-known risk factor for decline in cognitive performance within the normal range of cognitive functioning, mild cognitive impairment (MCI) and dementia. It is important to emphasize 3 features of the review: (1) it is not designed as a critical review of the literature, but rather to describe the historical influences on our current knowledge base (poor, mediocre and outstanding papers from the past have all shaped our present); (2) word-count limitations require that we omit statistical detail except to emphasize effect sizes in pivotal papers; and (3) each milestone topic is addressed by noting the earliest work then followed by examples of papers representing pivotal events. A number of comprehensive reviews of this literature are available, 2-6 including a seminal paper summarizing the formative years of this research.7 Please see http://hyper.ahajournals.org for citations to additional reviews of the literature and papers published in Hypertension. We recognize the importance of the emerging literature on hypotension and cognitive function, but refer the readers to previous reviews which include this topic. 8-10 Measurement of Cognitive FunctioningIn this paper, the term cognitive performance is used to describe the outcome of studies measuring a full range of ability from low to high. The term cognitive functioning is used to describe, more generally, findings with respect to cognitive performance, MCI, or dementia. Cognitive deficit is used in a comparative sense, hypertensive individuals compared to some other group of subjects. The term impairment is used to indicate clinically significant cognitive dysfunction. Lezak et al11 provide a compendium of over 700 psychometric tests and subtests. They describe behaviors required to perform the test, the latent abilities that the tests purport to measure, eg, working memory, attention, and executive functioning. Classic neuropsychological texts describe how tests and the latent cognitive constructs they measure are used to make inferences about the hemisphere, locus, and extent of brain injury.12 Figure 1 shows an example of a hypothetical study in which tests are being used to explore the hypothesis that hypertension is more strongly associated with executive functioning 13 and that this phenomenon is associated with reduced cerebral blood flow (CBF) to the frontal and prefrontal brain areas, but not to other brain areas.14 Executive functioning (EF) can be defined as t...

The conditions of chronic obesity and overweight status are risk factors for lower cognitive performance, cognitive decline, cognitive deficit, and dementia. But lower cognitive performance early in life itself may be a risk factor for an increase in body weight over time. With this in mind, we review important papers in the literature that advance our knowledge of relations between weight and cognitive functioning, with an emphasis on papers that illustrate methodological and theoretical issues of importance. We describe the evolution in research on weight and cognition with respect to two major features: (a) the move backward in time from the diagnosis of dementia to the pre-clinical period of dementia in order to better identify risk factors; and (b) the evolution of studies from an earlier emphasis on obesity-related cardiovascular risk factors as major mediators of relations between obesity and cognition to a more recent emphasis on metabolic variables, lifestyle variables, genotype, and other mechanisms that explain relations among weight change, obesity, and cognition. We conclude that: 1) a complete understanding of the causal links between weight and cognitive functioning requires a lifespan perspective; 2) practically speaking, lifespan research may need to amalgamate and integrate research at different segments of the lifespan until such time that we can include the entire life cycle within a single study of weight and cognition; and 3) we need more studies that examine reciprocal relations between weight and cognition, especially early in life.

PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbestos inhalation. We have studied the interaction of chrysotile asbestos fibers with rat lung fibroblasts (RLF) in vitro and the consequent changes in PDGF receptor mRNA expression, PDGF binding, and mitogenic activity of PDGF isoforms. Northern blot analysis revealed that mRNA for the PDGF-receptor a subtype (PDGF-Ra) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 tug fibers/cm2). I125IIPDGF-BB receptor assays showed that normal RLF possess mainly PDGF-R,# and a paucity of PDGF-Ra. In agreement with the Northern data, saturation binding of I'25IIPDGF-BB to RLF exposed to asbestos demonstrated an -40% increase in binding sites accompanied by a twofold decrease in receptor affinity. Treating asbestos-exposed RLF with PDGF-AA, which binds only PDGF-Ra, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had increased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses. These data show that inorganic particulates alter the PDGF-Ra population on RLF without significant change in PDGF-Rfi. (J. Clin. Invest. 1993. 92:425-430.)

No abstract

The primary objective of this study was to provide supplementary normative data on aging and cognition from an ongoing community-based study. This dementia- and stroke-free sample (age range = 70-89; mean = 77.5) consisted of 228 women and 155 men participating in the Maine-Syracuse Longitudinal Study at waves 6 to 7 (2001-2009). The authors employed a battery of 23 widely utilized clinical cognitive tests. In this cross-sectional study, the authors focus on subjects 70 to 79 (n = 248) and 80 to 89 (n = 135) years old, and provide preliminary data for a smaller number of subjects aged 90 to 98 years old (n = 14). More highly educated and younger participants exhibited better performance on cognitive tests. Education was not significantly associated with every cognitive outcome, nor was age cohort membership. The addition of cardiovascular disease (CVD)/health variables to a model including age, education, and gender main effects provided statistically significant increases in R² (range = .021-.084) of performance on some tests. Results are discussed in relation to this study's value with respect to determining cognitive impairment in individuals free from probable dementia or stroke.