Alterations in the human intestinal microbiota are linked to conditions including inflammatory bowel disease, irritable bowel syndrome, and obesity. The microbiota also undergoes substantial changes at the extremes of life, in infants and older people, the ramifications of which are still being explored. We applied pyrosequencing of over 40,000 16S rRNA gene V4 region amplicons per subject to characterize the fecal microbiota in 161 subjects aged 65 y and older and 9 younger control subjects. The microbiota of each individual subject constituted a unique profile that was separable from all others. In 68% of the individuals, the microbiota was dominated by phylum Bacteroides, with an average proportion of 57% across all 161 baseline samples. Phylum Firmicutes had an average proportion of 40%. The proportions of some phyla and genera associated with disease or health also varied dramatically, including Proteobacteria, Actinobacteria, and Faecalibacteria. The core microbiota of elderly subjects was distinct from that previously established for younger adults, with a greater proportion of Bacteroides spp. and distinct abundance patterns of Clostridium groups. Analyses of 26 fecal microbiota datasets from 3-month follow-up samples indicated that in 85% of the subjects, the microbiota composition was more like the corresponding time-0 sample than any other dataset. We conclude that the fecal microbiota of the elderly shows temporal stability over limited time in the majority of subjects but is characterized by unusual phylum proportions and extreme variability.

OBJECTIVE:To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E 4 versus those without E 4 had poorer memory performance (mean score difference À 0.20 (95% confidence interval (CI) 5 À 0.31 to À 0.09) for immediate recall and À 0.32 (95% CI 5 À 0.48 to À 0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI 5 1.20-4.28); Letter-Digit score, À 0.36, (95% CI 5 À 0.77-0.05). Subjects with apolipoprotein E 4 showed a greater decline in immediate ( À 0.22, 95% CI 5 À 0.33 to À 0.11) and delayed ( À 0.30, 95% CI 5 À 0.46 to À 0.15) memory scores but no significant change in speed of information processing (Stroop, P 5.17; Letter-Digit, P 5.06). Memory scores decreased 2.5% from baseline in those without E 4 , 4.3% in E 4 heterozygotes (P 5.01 for immediate and P 5.03 for delayed, vs no E 4 ) and 8.9% to 13.8% in E 4 homozygotes (P 5.04 for immediate and P 5.004 for delayed, vs heterozygotes). Apolipoprotein E 4 was associated with greater decline in instrumental activities of daily living (Po.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E 4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. J Am Geriatr Soc 55:1777-1785, 2007. Key words: memory; dementia; trial; statin A major challenge in the quest to promote healthy aging is to uncover the determinants of cognitive decline in the general population and the risk factors that lead to the development of frank dementia. Although age is the main predictor of cognitive function, investigators have also reported that a history of hypertension, diabetes mellitus, stroke, depression, and lack of physical activity are factors. [1][2][3][4][5][6] The apolipoprotein E phenotype (apolipoprotein E is coded by a gene (e) that exhibits allelic variants e 2 , e 3 , and e 4 ) has been linked consistently and strongly to the appearance of Alzheimer's disease and to some aspects of cognitive decline in elderly cohorts. 1,2,[5][6][7][8][9] Inheritance of E 4 (the product of e 4 ) especially in the homozygous form, has been associated in cross-sectional studies with risk of Alzheimer's disease and poorer global cognitive function, episodic memory, and executive function, although the magnitude of the effect is modest. 10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's diseas...