Incidence of cognitively defined late-onset Alzheimer\u27s dementia subgroups from a prospective cohort study.

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer\u27s dementia. METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer\u27s dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer\u27s dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer\u27s-related neuropathology, and higher proportions with other Alzheimer\u27s dementia genetic risk variants. DISCUSSION: A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer\u27s dementia

An Integrated Framework for Optimizing CO₂ Sequestration and Enhanced Oil Recovery

CO₂-enhanced oil recovery (CO₂-EOR) is a technique for commercially producing oil from depleted reservoirs by injecting CO₂ along with water. Because a large portion of the injected CO₂ remains in place, CO₂-EOR is an option for permanently sequestering CO₂. This study develops a generic integrated framework for optimizing CO₂ sequestration and enhanced oil recovery based on known parameter distributions for a depleted oil reservoir in Texas. The framework consists of a multiphase reservoir simulator coupled with geologic and statistical models. An integrated simulation of CO₂–water–oil flow and reactive transport is conducted, followed by a global sensitivity and response surface analysis, for optimizing the CO₂-EOR process. The results indicate that the reservoir permeability, porosity, thickness, and depth are the major intrinsic reservoir parameters that control net CO₂ injection/storage and oil/gas recovery rates. The distance between injection and production wells and the sequence of alternating CO₂ and water injection are the significant operational parameters for designing a five-spot CO₂-EOR pattern that efficiently produces oil while storing CO₂. The results from this study provide useful insights for understanding the potential and uncertainty of commercial-scale CO₂ sequestrations with a utilization component

Associations Between Depression, Traumatic Brain Injury, and Cognitively-Defined Late-Onset Alzheimer\u27s Disease Subgroups.

BACKGROUND: There is considerable heterogeneity in clinical presentation among people with late-onset Alzheimer\u27s disease (LOAD). We have categorized people with LOAD into subgroups based on relative impairments across cognitive domains. These 6 groups are people with no relatively impaired domains (AD-No Domains), 4 groups with one relatively impaired domain (AD-Memory, AD-Executive, AD-Language, and AD-Visuospatial), and a group with multiple relatively impaired domains (AD-Multiple Domains). Our previous analysis demonstrated that genetic factors vary across cognitively-defined LOAD groups. OBJECTIVE: To determine whether risks associated with depression and traumatic brain injury with loss of consciousness (TBI) for cognitively defined LOAD subgroups are similar. METHODS: We used cognitive data at LOAD diagnosis from three prospective cohort studies to determine cognitively-defined subgroups. We compared subgroups in endorsement of items from the Centers for Epidemiological Studies Depression (CES-D) scale and history of TBI. RESULTS: Among 1,505 people with LOAD from the three studies, there were substantial differences across subgroups in total CES-D score, with lower scores (less depression) for people with AD with relative impairments in memory (AD-Memory) compared to those in other groups. Differences were noteworthy for the sleep-related item of the CES-D, as people with AD-Memory were less likely to report restless sleep than people in other groups. There were no differences in TBI history across groups. CONCLUSIONS: Differences in risk factor associations across subgroups such as differences in endorsement of depression symptoms and restless sleep provide support for the hypothesis that there are biologically coherent subgroups of AD

Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups

Categorizing people with late-onset Alzheimer's disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer's disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p < 10-5 and odds ratios more extreme than those previously reported for Alzheimer's disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10-27). Across subgroups, there were 33 novel suggestive loci across the genome with p < 10-5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.R01 AG042437/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG029672/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ K23 AG046377/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ U01 AG042904/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ P30 AG010133/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG019771/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ P50 AG005136/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ K01 AG050699/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ P50 AG005133/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG030653/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG041718/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG017917/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ U01 AG032984/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ R01 AG030146/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ U01 AG006781/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ U01 HG006375/U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ P50 AG005136/AG/NIA NIH HHS/United States P50 AG005133/AG/NIA NIH HHS/United States K23 AG046377/AG/NIA NIH HHS/United State