Journal of Alzheimer's Disease - Volume 33, issue s1

Authors: Lopez, Oscar L. | Becker, James T. | Kuller, Lewis H.

Article Type: Review Article

Abstract: Alzheimer's disease (AD) is the most frequent form of dementia in elderly individuals and its incidence and prevalence increases with age. This risk of AD is increased in the presence of genetic and demographic factors including apolipoprotein E 4 allele, lower education, and family history of AD. There are medical risk modifiers including systemic hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease that increase the vulnerability for AD. By contrast, there are lifestyle risk modifiers that reduce the effects of AD risk factors include diet and physical and cognitive activity. Our research has consistently shown that it is the interactions …among these risk factors with the pathobiological cascade of AD that determine the likelihood of a clinical expression of AD—either as dementia or mild cognitive impairment. However, the association between “vulnerability” and “protective” factors varies with age, since the effects of these factors on the risk for AD may differ in younger (age < 80) versus older (age > 80) individuals. The understanding of the dynamic of these factors at different age periods will be essential for the implementation of primary prevention treatments for AD. Show more

Keywords: Alzheimer's disease, cardiovascular disease, cerebrovascular disease, mild cognitive impairment

DOI: 10.3233/JAD-2012-129015

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S427-S438, 2013

Authors: Weinstein, Galit | Wolf, Philip A. | Beiser, Alexa S. | Au, Rhoda | Seshadri, Sudha

Article Type: Review Article

Abstract: The study of Alzheimer's disease (AD) in the Framingham Heart Study (FHS), a multi-generational, community-based population study, began nearly four decades ago. In this overview, we highlight findings from seven prior publications that examined lifetime risk estimates for AD, environmental risk factors for AD, circulating and imaging markers of aging-related brain injury, and explorations on the genetics underlying AD. First, we describe estimations of the lifetime risk of AD. These estimates are distinguished from other measures of disease burden and have substantial public health implications. We then describe prospective studies of environmental AD risk factors: one examined the association between …plasma levels of omega-3 fatty-acid and risk of incident AD, the other explored the association of diabetes to this risk in subsamples with specific characteristics. With evidence of inflammation as an underlying mechanism, we also describe findings from a study that compared the effects of serum cytokines and spontaneous production of peripheral blood mononuclear cell cytokines on AD risk. Investigating AD related endophenotypes increases sensitivity in identifying risk factors and can be used to explore pathophysiologic pathways between a risk factor and the disease. We describe findings of an association between large volume of white matter hyperintensities and a specific pattern of cognitive deficits in non-demented participants. Finally, we summarize our findings from two genetic studies: The first used genome-wide association (GWA) and family-based association methods to explore the genetic basis of cognitive and structural brain traits. The second is a large meta-analysis GWA study of AD, in which novel loci of AD susceptibility were found. Together, these findings demonstrate the FHS multi-directional efforts in investigating dementia and AD. Show more

Keywords: Alzheimer's disease, cerebrovascular disorders, cohort studies, genetic variation, risk factors

DOI: 10.3233/JAD-2012-129040

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S439-S445, 2013

Authors: Devanand, Devangere | Lee, Joseph | Luchsinger, Jose | Manly, Jennifer | Marder, Karen | Mayeux, Richard | Scarmeas, Nikolaos | Schupf, Nicole | Stern, Yaakov

Article Type: Review Article

Abstract: This review summarizes the findings and importance of 12 articles from research at Columbia University in New York City that were among the most cited in the literature between 2006 and 2011. The 12 articles summarized in this review made important contributions to the field of Alzheimer's disease in the last 5 years. Four of the articles established the Mediterranean diet as a food consumption pattern that may prevent Alzheimer's disease in addition to physical activity. Two of the articles advanced our knowledge of predictors of conversion from mild cognitive impairment to dementia. Four of the articles provided important knowledge …of risk factors for the progression of Alzheimer's disease and its complications. Lastly, one of the articles laid the theoretical framework for the study of cognitive reserve, an important modifier of the manifestation of Alzheimer's disease. These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease. Show more

Keywords: Alzheimer's disease, conversion, diet, cognitive reserve, epidemiology, genes, mild cognitive impairment, predictors, progression, risk factors

DOI: 10.3233/JAD-2012-129041

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S447-S455, 2013

Authors: Barberger-Gateau, Pascale | Lambert, Jean-Charles | Féart, Catherine | Pérès, Karine | Ritchie, Karen | Dartigues, Jean-François | Alpérovitch, Annick

Article Type: Review Article

Abstract: Late-life dementia results from non-modifiable risk factors such as age and genetics, modulated by deleterious and protective environmental factors among which nutrition may play a major role. This paper highlights five major recent contributions of the French Three-City (3C) and PAQUID epidemiological studies to Alzheimer's disease (AD) knowledge, targeting genetic and dietary risk factors, and the impact of cognitive decline in daily living. The 3C study contributed to a large genome-wide association study to identify new genetic risk factors for AD. In addition to apolipoprotein E (APOE), two loci gave replicated evidence of association: one within CLU, encoding clusterin or …apolipoprotein J, and the other within CR1, encoding the complement component receptor 1. Although the attributable fraction of risk for these polymorphisms is moderate, genetic studies provide significant insights into the molecular bases of AD. Regarding dietary data, findings from 3C suggest that healthy diets associating sources of both omega 3 fatty acids (fish) and antioxidants (fruits and vegetables) such as the Mediterranean diet, and caffeine could be associated with decreased risk for AD. However, the protective effect of omega3 fatty acids might be limited to APOE4 non-carriers. Future research should focus on gene-nutrient interactions. Regarding the functional impact of prodromal AD, the PAQUID study showed that taking into account mild functional limitations considerably increases the predictive value of neuropsychological tests for conversion to dementia. Research should focus on sensitive instruments to capture early functional decline to improve the identification of elderly patients at high risk of conversion to dementia. Show more

Keywords: Activities of daily living, Alzheimer's disease, caffeine, cohort studies, dementia, epidemiology, genome-wide association study, Mediterranean diet

DOI: 10.3233/JAD-2012-129019

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S457-S463, 2013

Authors: Solomon, Alina | Kivipelto, Miia | Soininen, Hilkka

Article Type: Review Article

Abstract: This is a brief summary of experiences from Finland related to Alzheimer's disease (AD) prevention research. The first signals that AD may have vascular modifiable risk factors came from studies on cardiovascular conditions and diabetes. Cardiovascular prevention projects such as North Karelia Project and WHO-MONICA in the 1970–1980 s were focused on younger populations, which led to the idea of looking for risk factors as far back as middle age. Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) is one of the few studies in the world focusing on late-life cognition with a large and representative population-based cohort, baseline …examination at midlife, and follow-up time up to three decades. Since 1998, it has identified several modifiable risk factors for cognitive impairment/dementia, and produced the first risk score for estimating dementia risk based on midlife profiles. The CAIDE Dementia Risk Score has been used to select participants in the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER). FINGER is an ongoing multicenter RCT involving 1,200 participants aged 60–77 years, and testing the effects of a two-year multi-domain intervention targeting several risk factors simultaneously. It started in September 2009 and will be completed at the end of 2013. The FINGER study is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia. Show more

Keywords: Alzheimer's disease cognitive impairment, epidemiology, prevention, randomized controlled trials

DOI: 10.3233/JAD-2012-129021

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S465-S469, 2013