A growing body of evidence from animal and human studies links dietary fat composition, blood lipids, and cholesterol to the development of dementia.
Cholesterol is central to the process of Alzheimer's disease. The primary genetic risk factor for late onset Alzheimer's disease is the apolipoprotein E (APOE)-e4 allele. Apolipoprotein E is involved in cholesterol transport. The composition of dietary fats affects levels of blood cholesterol and other circulating lipids.
Of the different types of dietary fats, saturated and trans fats increase blood LDL-cholesterol. Blood cholesterol level and a hypercholesterolemic diet have been associated with cognitive decline, Alzheimer's disease and brain neuropathology. Recent studies in animal models and in humans suggest that the deleterious effects of these hypercholesterolemic diets on the brain may be far worse in the presence of dietary copper. The n-3 class of polyunsaturated fat (PUFA) obtained from marine and plant sources has been associated with slower rate of cognitive decline and lower risk of developing Alzheimer's disease. The n-3 PUFA, docosahexaenoic acid (DHA) has been targeted as particularly important for brain function, and is the primary lipid in the most metabolically active areas of the brain. Several randomized clinical trials are currently underway to test the effects of n-3 fatty acid supplementation on cognitive decline and the development of Alzheimer's disease.

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In order to know how to live longer and healthy, we conducted centenarian study with multidisciplinary approach since 2000. We presented here the results of our study. The characteristics of centenarians are 1) low prevalence of diadetes mellitus, 2) frequency of illness is 97%,3) prevalence of dementia free and independent centenarian is 18%, 4)low level of albumin, 5) low-grade activation of inflammation, 6) high level of adiponectin. We proposed aging-inflammation hypothesis. Since centenarian is not the model of healthy longevity, we began to study semisupercentenarians (SSC). SSC are considered to be a real model of human longevity. Whole genome scan of both SSC and control group, is now in progress. We hope that longevity genes will identified within a few years.

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Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection, and the return to homeostasis. Systematic metabolomic studies of lipid mediators in the course of acute inflammatory responses revealed that ω3 polyunsaturated fatty acid-derived mediators are generated within resolving exudates, including resolvin E1 from eicosapentaenoic acid (EPA) and protectin D1 from docosahexaenoic acid (DHA). These products proved to be potent inhibitors of neutrophil infiltration, cytokine productions, and promote resolution by increasing macrophage ingestion of apoptotic cells and clearance from exudates. These results established novel arrays of bioactive lipid mediators derived from ω3 fatty acids by leukocytes during cell-cell interactions that regulate acute inflammation and promote resolution.

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In 2002, the Japan Society for Lipid Nutrition (JSLN) adopted a proposal that the direction of lipid nutrition for the prevention of life-style related diseases should be changed so as to reduce the intake of linoleic acid (ω6) from the current levels of 5∼6 energy %. Since then, nutritional guidelines began to be documented in terms of RDA (recommended dietary allowance), AI (adequate intake), DG (dietary goal) and⁄or UL (Upper limit), and I propose that JSLN should also discuss the values for these parameters. To begin with the discussion, I propose 2∼3 energy % as AI, 3 energy % as DG and <4 energy % as UL for adults consuming ω3 fatty acids included in average Japanese meals. The <10 energy % as UL or as DG proposed by other organizations is inconsistent with our Society's decision, and was critically evaluated; the risk of increasing linoleic acid up to 10 energy % was emphasized.

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Though the fat are necessary to a body, it is a nutrient given a wide unfavorable compound in our country. The starting point of this minus image is measures of the cardiovascular disease that the U.S. Government shows the high prevalence in the country. As the nutrition guidance for anti- cardiovascular disease, decrease of the meal intake fat was carried out politically. The harm that had too much a fat intake, the fat heavy theory was that is to say proposed by McGovern report. The U.S. Government spent enormous expense and time and a talented person to prove this opinion, but the clinical data to support was not provided. The U.S. Government carried out the large-scale intervention examination of the long term of low-fat dietary, but the risk of a cardiovascular disease and breast cancer and the colorectal cancer did not fall down.
This proof was important as a political measure, but failed clinically. Adaptation to our country by the literal translation of the McGovern report led to the spread of the minus image of fat. The cause of the mistake is the difference of the fat intake volume between Japan and U.S.A. and a difference of the nutrient-related genetic polymorphism of the two countries.
If we control total calorie intake and enforce an exercise custom, we can erase the negative action of fats.

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Shirasaki published a Japanese paper about the relationship between total cholesterol levels and all-cause mortality in Fukui City, Japan. His cholesterol data were not grouped according to ordinal 20mg⁄dL (0.52 mmol⁄L) intervals. In the present study, we re-calculated his data for meta-analysis. The relative risk (RR) of all-cause mortality adjusted for age and sex showed a decreasing trend with total cholesterol levels (p for trend <0.0001).
In order to summarize the relationship between total cholesterol and all-cause mortality, literature describing this relationship in Japan was collected mainly using computer search engines. Literature published before 1995 was excluded. Reports with the total number of study subjects smaller than 5,000 were also excluded. Five reports were found suitable for meta-analysis of cholesterol levels and all-cause mortality. Meta-analysis revealed that the RR in the <160 mg⁄dL (<4.14 mmol⁄L) group [RR=1.71 (1.41, 2.08)] was significantly higher than in the reference group [160-199 mg⁄dL (4.14-5.17 mmol⁄L)], and that the RRs in the 200-239 mg⁄dL (5.18-6.21 mmol⁄L) group [RRs=0.83 (0.74, 0.94)] and ≥240 mg⁄dL (≥6.22 mmol⁄L) group [0.78 (0.65, 0.95)] were significantly lower than in the reference group when both men and women were combined. We suggest that Japanese subjects with cholesterol levels ≥240 mg⁄dL (≥6.22 mmol⁄L) should not be regarded as hypercholesterolemic or dyslipidemic except when having some genetic disorders like familial hypercholesterolemia because they are in the safest ranges in terms of all-cause mortality.

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