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      The effects of cardiovascular risk factors on cognitive compromise Translated title: Los efectos de los factures de riesgo cardiovascular en el compromiso cognitivo Translated title: Les effets des facteurs de risque cardiovasculaire sur le déficit cognitif

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          Abstract

          As life expectancy in the United States continues to increase, the projected numbers of elderly people who will develop dementia will grow rapidly. This paper reviews four well-established cardiovascular risk factors (type 2 diabetes, hypertension, cholesterol, and inflammation), for which there is longitudinal epidemiological evidence of increased risk of dementia, Alzheimer's disease, mild cognitive impairment, and cognitive decline. These risk factors are of special interest because of their potential modif lability, which may affect the course of cognitive compromise. Diabetes is the cardiovascular risk factor (CvRF) most consistently associated with cognition. Hypertension in midlife is consistently associated with cognition, but its associations with late-life hypertension are less clear. Total cholesterol is not consistently associated with cognition, interleukin-6 and C-reactive protein are inflammatory markers relatively consistently associated with cognition. Composites of the CvRFs increase the risk for dementia in a dose-dependent fashion, suggesting a cumulative effect of these factors on neuronal stress. In the relatively few studies that have reported interactions of risk factors, they potentiate each other. The effect of each of these risk factors varies according to apolipoprotein E genotype, it may be that the effect of these risk factors varies according to the presence of the others, and these complex relationships underlie the biological mechanisms of cognitive compromise. This may be crucial for understanding the effects on cognition of druqs and other approaches, such as lifestyle chanqe, for treatinq these risk factors.

          Translated abstract

          Dado que la expectativa de vida en los Estados Unidos continúa incrementándose, el número proyectado de personas de edad avanzada que desarrollarán demencia crecerá rápidamente. Este artículo revisa cuatro factores de riesgo cardiovascular bien establecidos (diabetes tipo 2, hipertensión, coleste-rol e inflamación), para los cuales existen evidencias epidemiológicas longitudinales de un riesgo aumentado de demencia, Enfermedad de Alzheimer, deterioro cognitívo leve y decaimiento cognitivo, Estos factores de riesgo son de especial interés ya que son potencial mente modificables, lo que puede influir en la evolución del compromiso cognitivo, La diabetes es el factor de riesgo cardiovascular (FRCv) que se asocia con mayor consistencia con la cognición. La hipertensión en la edad media de la vida está asociada consistentemente con la cognición, pero las asociaciones de esta última con la hipertensión de las etapas tardías de la vida son menos claras. El coles-terol total no está asociado consistentemente con la cognición. La interleukina 6 y la proteína C reactiva son marcadores inflamatorios con una asociación relativamente consistente con la cognición. Una combinación de los FRCv aumenta el riesgo para demencia de manera dosis-dependiente, lo que sugiere un efecto acumulativo de estos factores de estrés neu-ronal. En los relativamente pocos estudios que han dado cuenta de las interacciones entre los factores de riesgo, estos se potencian unos con otros, El efecto de cada uno de los factores de riesgo varía de acuerdo con el genotipo para la apolipoproteína £ Puede ser que el efecto de estos factores de riesgo se modifique según la presencia de los otros, y estas complejas relaciones estén a la base de los mecanismos biológicos del compromiso cognitivo. Para el tratamiento de los factores de riesgo puede ser crucial comprender los efectos que tienen en la cognición los fármacos y otras intervenciones, como el cambio de estilo de vida.

          Translated abstract

          L'espérance de vie continuant à augmenter aux Étais-Unis, le nombre de sujets âgés qui développeront une démence est appelé à augmenter rapidement. Cet article examine quatre facteurs de risque cardiovasculaire bien connus (diabète de type 2, hypertension, cholestérol et inflammation) qui ont montré lors d'études épidémiologiques longitudinales qu'ils présentaient un risque accru de démence, de maladie d“ Alzheimer, de déficit cognitif léger et de déclin cognitif. Ces facteurs de risque sont très intéressants car ils peuvent être modifiés, ce qui pourrait influencer l'évolution du déclin cognitif. Le diabète est le facteur de risque cardiovasculaire (FRCv) le plus régulièrement associé à la cognition. L'hypertension des sujets d'âge moyen semble liée aux capacités cognitives, ce qui apparaît moins important chez les sujets plus âgés. Le cholestérol total n'est pas corrêlé à la cognition alors que les marqueurs de l'inflammation interleukine-6 et protéine-réactive C le seraient relativement Les FRCv augmenteraient le risque de démence de façon dose-dépendante, avec un potentiel effet cumulatif sur le stress neuronal. Dans les relativement rares études qui ont rapporté des interactions des facteurs de risque, ces derniers semblaient se poteniialiser les uns les autres. Par ailleurs, l'effet de chacun d'entre eux varierait selon le génotype de l'apolipoprotéine E. L'effet de ces facteurs de risque pourrait varier en fonction de la présence des autres et ces relations complexes sous-tendent les mécanismes biologiques du déficit cognitif. Leur étude apparaît cruciale pour la compréhension des effets des médicaments et d'autres approches thérapeutiques (modification du style de vie) sur la cognition, afin de traiter ces facteurs de risque.

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          The metabolic syndrome, inflammation, and risk of cognitive decline.

          Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition. To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation. A 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sites. A total of 2632 black and white elders (mean age, 74 years). Association of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years. Cognitive impairment was defined as at least a 5-point decline. Compared with those without the metabolic syndrome (n = 1616), elders with the metabolic syndrome (n = 1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02-1.41). There was a statistically significant interaction with inflammation and the metabolic syndrome (P = .03) on cognitive impairment. After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n = 348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 1.66; 95% CI, 1.19-2.32). Those with the metabolic syndrome and low inflammation (n = 668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 1.08; 95% CI, 0.89-1.30). Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P = .04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P = .44). These findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation.
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            Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype.

            Raising insulin acutely in the periphery and in brain improves verbal memory. Intranasal insulin administration, which raises insulin acutely in the CNS without raising plasma insulin levels, provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes. Based on prior research with intravenous insulin, we predicted that the treatment response would differ between subjects with (epsilon4+) and without (epsilon4-) the APOE-epsilon4 allele. On separate mornings, 26 memory-impaired subjects (13 with early Alzheimer's disease and 13 with amnestic mild cognitive impairment) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline (placebo) or insulin (20 or 40 IU). Cognition was tested 15 min post-treatment, and blood was acquired at baseline and 45 min after treatment. Intranasal insulin treatment did not change plasma insulin or glucose levels. Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults. These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4+ subjects and normal adults. Unexpectedly, memory-impaired epsilon4+ subjects showed poorer recall following insulin administration on one test of memory. These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E (APOE) related differences in insulin metabolism.
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              15-year longitudinal study of blood pressure and dementia.

              Vascular causes of dementia may be more common than supposed. Vascular factors may also have a role in late-onset Alzheimer's disease, but the role of hypertension in the development of dementia is unclear. As part of the Longitudinal Population Study of 70-year-olds in Göteborg, Sweden, we analysed the relation between blood pressure and the development of dementia in the age intervals 70-75, 75-79, and 79-85 years in those non-demented at age 70 (n = 382). The sample was followed up for 15 years and examined repeatedly with a comprehensive investigation, including a psychiatric and physical examination. a Participants who developed dementia at age 79-85 had higher systolic blood pressure at age 70 (mean 178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages 70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did not develop dementia. For subtypes of dementia, higher diastolic blood pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's disease and at age 75 (101, p = 0.015) for those developing vascular dementia than for those who did not develop dementia. Participants with white-matter lesions on computed tomography at age 85 had higher blood pressure at age 70 than those without such lesions. Blood pressure declined in the years before dementia onset and was then similar to or lower than that in non-demented individuals. Previously increased blood pressure may increase the risk for dementia by inducing small-vessel disease and white-matter lesions. To what extent the decline in blood pressure before dementia onset is a consequence or a cause of the brain disease remains to be elucidated.
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                Author and article information

                Contributors
                Mount Sinai School of Medicine, New York, NY, USA
                Sheba Medical Center, Ramat Gan, Israel
                Mount Sinai School of Medicine, New York, NY, USA
                Mount Sinai School of Medicine, New York, NY, USA
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                June 2009
                : 11
                : 2
                : 201-212
                Affiliations
                Mount Sinai School of Medicine, New York, NY, USA
                Sheba Medical Center, Ramat Gan, Israel
                Mount Sinai School of Medicine, New York, NY, USA
                Mount Sinai School of Medicine, New York, NY, USA
                Author notes
                Article
                10.31887/DCNS.2009.11.2/msbeeri
                3093131
                19585955
                85255e07-832f-4506-9589-1492ace879b2
                Copyright: © 2009 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Clinical Research

                Neurosciences
                cognitive decline,mild cognitive impairment,alzheimer's disease,diabetes,dementia,inflammation,hypertension,cholesterol

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