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Insulin Resistance as a Risk Factor for Alzheimer's Disease
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Miren Ettcheto, Amanda Cano, Elena Sanchez-Lopez, Carme Auladell, Jaume Folch, Antoni Camins
The Rotterdam study was the first to propose the connection between these two pathologies, revealing that diabetes increases the risk of dementia (20, 21). Later, clinical and epidemiological studies have confirmed this association, demonstrating that the alteration of metabolic parameters, such as hyperglycemia and hyperinsulinemia, are positively correlated with the development of LOAD neuropathology. In this line, the Hisayama Study investigates the pathways through which diabetes could influence the pathogenic process of this neurodegenerative disease, evaluating the formation of neuritic plaques and NFTs (12). In this study, the authors examined 2,520 subjects who underwent a metabolic characterization based on blood tests, which included the oral glucose tolerance test (OGTT) profiles of 75 g and fasting insulin levels. Subsequently, the pathology of LOAD was evaluated. Likewise, the authors also examined the combined effects of APOEε4 genotype associated with diabetes-related factors on the risk of the main hallmarks of LOAD, Aβ plaques and NFTs. The study found an association between diabetes plus APOEε4 and Aβ plaques, but not with NFT formation (12).
Successful Aging in Research
Published in Thomas S. Inui, Richard M. Frankel, Enhancing the Professional Culture of Academic Health Science Centers, 2022
Bruce M. Psaty, David S. Siscovick
The requirements for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration. In the late 2000s, GWAS consortia were typically organized around a particular phenotype such as glucose, lipids, or some form of cancer. The primary innovation provided by the CHARGE consortium, formed in February 2008, is the use of the cohort design as the organizing principle. The initial design of the CHARGE Consortium included five prospective aging and cardiovascular cohort studies that first had completed GWAS data from the United States and Europe: Age, Gene/Environment Susceptibility (AGES) Study, ARIC, CHS, FHS and the Rotterdam Study. Subsequently, other studies such as MESA and CARDIA have joined.
Health and Economic Burdens of Diabetes and Its Complications
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Studies such as the Rotterdam Study and the Honolulu Aging Study have shown a significantly increased risk of development of dementia in patients with diabetes mellitus.19 Alzheimer disease (AD) is the most common cause of dementia in North America.19 Sporadic AD, which makes up approximately 90% of the incidence of AD (5%–10% of the incidence of AD is inheritable), is thought to be related to the effects of brain insulin and IGF resistance.19 The brain insulin resistance and its adverse impact on IGF-1 and IGF-2 networks is thought to lead to the reduced activation of the receptors and the resultant decreased downstream neuronal survival and plasticity mechanisms.19 As a result of this and other related findings, some researchers have proposed that AD be reclassified as type 3 diabetes.19 There is also thought to be an association between diabetes mellitus and vascular dementia, with several studies suggesting that type 2 diabetes contributes to both AD and vascular dementia.20 The physiologic milieu and the vascular changes associated with diabetes may contribute to some of the changes that are commonly associated with vascular dementia in some individuals. These changes include white matter hyperintensities, cerebral microbleeds, silent infarcts, and cerebral atrophy.21 Also, the Atherosclerosis Risk in Communities Study showed a fourfold increase in “strokes” in patients with diabetes mellitus when compared to non-diabetic controls, with a correlation noted with their degree of hyperglycemia, based on HgbA1c levels.17
Discrimination of degrees of auditory performance from the digits-in-noise test based on hearing status
Published in International Journal of Audiology, 2020
Nicole M. Armstrong, Berthe C. Oosterloo, Pauline H. Croll, Mohammad Arfan Ikram, André Goedegebure
This cross-sectional study was embedded in the Rotterdam Study, a prospective cohort study of determinants and consequences of aging (Ikram et al. 2017). Enrolment criteria are described in more detail elsewhere (Ikram et al. 2017). Briefly, from the population registry of Ommoord, a suburb of Rotterdam, The Netherlands, adults aged ≥45 years were invited to participate in the Rotterdam Study. Enrolment took place on a voluntary basis. In 2011, hearing assessments were introduced into the study protocol. This study included participants with both completed pure-tone audiometry and DIN (N = 3667). Participants were excluded if their SRT was greater than two standard deviations (SD) above the mean (n = 169) or their PTA was >50 dB HL (n = 76) to avoid that the noise would be presented below threshold levels. Exclusion criteria were defined to ensure the examination of the comprehension of digits through the background noise and lack of reliability with large intra-test SD. The DIN would be a test of hearing ability if the participant did not comprehend the digits through the background noise. The analytic sample consisted of 3422 participants. The institutional review board (Medical Ethics Committee) and the review board of The Netherlands Ministry of Health, Welfare, and Sports approved this study, and participants provided written informed consent.
Antihypertensive agents in Alzheimer’s disease: beyond vascular protection
Published in Expert Review of Neurotherapeutics, 2020
Thibaud Lebouvier, Yaohua Chen, Patrick Duriez, Florence Pasquier, Régis Bordet
Among VRFs, hypertension, diabetes, and dyslipidemia are readily modifiable with established therapeutic strategies [8]. But midlife hypertension is generally viewed as one of the main evitable VRF for cognitive decline and AD [2,6,7,9,10]. Midlife high blood pressure (BP) was also associated with an increase of white matter lesion, and smaller brain volumes [9]. Many studies have tried to answer the question of whether antihypertensive agents can prevent or slow down AD. There is a wealth of observational studies showing that the use of antihypertensive therapy is associated with a lesser incidence or prevalence of cognitive impairment and dementia [10–16]. With the exception of the Rotterdam Study cohort, where the decrease of the relative risk for AD was not significant [12], most studies yielded the same results when separating AD from all-type dementia [10,12–16]. Four pivotal prospective observational studies were performed in population-based cohorts [13,14,16,17]. Interestingly, the Honolulu-Asia Aging Study and the Rotterdam Study showed a positive correlation between the reduction of AD risk and duration of exposure to antihypertensive drugs, supporting a mechanistic link between antihypertensive drug use and AD prevention [14,16].
The Longitudinal and Cross-Sectional Associations of Grief and Complicated Grief With Sleep Quality in Older Adults
Published in Behavioral Sleep Medicine, 2019
Jelena Milic, Heidi Saavedra Perez, Lisette A. Zuurbier, Paul A. Boelen, Judith A. Rietjens, Albert Hofman, Henning Tiemeier
This study was embedded in The Rotterdam Study, an ongoing prospective cohort of older adults designed to examine the occurrence and risk factors of chronic diseases. The study design and objectives are described in Hofman et al. (2013). The Rotterdam Study comprises two cohorts, which were combined in the current analysis. Between 2002 and 2005, complicated grief and sleep quality were assessed during a home interview, referred to as baseline. The baseline interview was conducted in 5,481 participants. Of these participants, 60 persons did not complete the grief or sleep questionnaire. This left 5,421 participants with assessment of grief and sleep characteristics for cross-sectional analysis. In part of the follow-up examination (2009– 2011), both components of sleep (duration and quality) were assessed at the research center. After an average of 6.33 years (SD = 0.42), 3,511 (80%) of the 4,601 surviving participants underwent the follow-up interview for sleep duration, and 3,003 (71%) for sleep quality. The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus Medical Center (Erasmus MC) and by the Ministry of Health of the Netherlands, implementing the Wet Bevolkingsonderzoek: ERGO (Erasmus Rotterdam Gezondheid Onderzoek; Population Studies Act: Rotterdam Study). All participants provided written informed consent to participate in the study and to obtain information from their treating physicians.