1. Surgery is associated with ventricular enlargement as well as cognitive and functional decline.

    Alzheimer's & Dementia 12(5):590 (2016) PMID 26610898 PMCID PMC4861667

    In preclinical studies, surgery/anesthesia contribute to cognitive decline and enhance neuropathologic changes underlying Alzheimer's disease (AD). Nevertheless, the link between surgery, anesthesia, apolipoprotein E ε4 (APOE ε4), and AD remains unclear. We performed a retrospective cohort analy...
  2. Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice.

    Journal of Ethnopharmacology 180:78 (2016) PMID 26785167 PMCID PMC4764102

    This study investigates the cognitive enhancing effects of the plant Centella asiatica which is widely used Ayurvedic and traditional Chinese medicine. The goal of this study was to determine the effects of a water extract of the medicinal plant Centella asiatica (CAW) on cognitive ability as we...
  3. Precision Medicine: Clarity for the Complexity of Dementia.

    The American Journal of Pathology 186(3):500 (2016) PMID 26724389 PMCID PMC4816691

    Three key elements to precision medicine are stratification by risk, detection of pathophysiological processes as early as possible (even before clinical presentation), and alignment of mechanism of action of intervention(s) with an individual's molecular driver(s) of disease. Used for decades i...
  4. The new world of retirement income security in America.

    American Psychologist 71(4):321 (2016) PMID 27159439

    We have entered a new world of retirement income security in America, with older individuals more exposed to market risk and more vulnerable to financial insecurity than prior generations. This reflects an evolution that has altered the historical vision of a financially secure retirement suppor...
  5. GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease.

    Movement Disorders 31(1):95 (2016) PMID 26296077 PMCID PMC4724255

    Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. We screened the GBA coding region for mutati...
  6. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.

    Alzheimer's Research & Therapy 8:25 (2016) PMID 27358067 PMCID PMC4928349

    Apolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our object...
  7. STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity.

    Journal of Alzheimer's Disease 51(2):391 (2016) PMID 26890746 PMCID PMC4961356

    Because STX is a selective ligand for membrane estrogen receptors, it may be able to confer the beneficial effects of estrogen without eliciting the deleterious side effects associated with activation of the nuclear estrogen receptors. This study evaluates the neuroprotective properties of STX i...
  8. Non-targeted lipidomics of CSF and frontal cortex grey and white matter in control, mild cognitive impairment, and Alzheimer's disease subjects.

    Acta Neuropsychiatrica 27(5):270 (2015) PMID 25858158

    We undertook a non-targeted lipidomics analysis of post-mortem cerebrospinal fluid (CSF), frontal cortex grey matter, and subjacent white matter to define potential biomarkers that distinguish cognitively intact subjects from those with incipient or established dementia. Our objective was to inc...
  9. Alterations in mitochondrial number and function in Alzheimer's disease fibroblasts.

    Metabolic Brain Disease 30(5):1275 (2015) PMID 25862550 PMCID PMC4800977

    Mitochondrial dysfunction is observed in brains of Alzheimer's Disease patients as well as many rodent model systems including those modeling mutations in preseinilin 1 (PSEN1). The aim of our study was to characterize mitochondrial function and number in fibroblasts from AD patients with PSEN1 ...
  10. Retirement patterns and the macroeconomy, 1992-2010: the prevalence and determinants of bridge jobs, phased retirement, and reentry among three recent cohorts of older americans.

    Gerontologist 55(3):384 (2015) PMID 24318800

    Older Americans contemplating retirement today face a very different economic environment than prior cohorts did. This article examines whether the retirement patterns of older Americans have changed as a result. Using data from 10 waves of the Health and Retirement Study (HRS), we examine the p...
  11. Cognitive profile of LRRK2-related Parkinson's disease.

    Movement Disorders 30(5):728 (2015) PMID 25650144 PMCID PMC4397146

    Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized....
  12. Cerebrospinal fluid peptides as potential Parkinson disease biomarkers: a staged pipeline for discovery and validation.

    Molecular & Cellular Proteomics 14(3):544 (2015) PMID 25556233 PMCID PMC4349976

    Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throu...
  13. Rarity of the Alzheimer disease-protective APP A673T variant in the United States.
    Li-San Wang, Adam C Naj, Robert Graham, Paul K Crane, Brian W Kunkle, Carlos Cruchaga, Josue D Gonzalez Murcia, Lisa Cannon-Albright, Clinton T Baldwin, Henrik Zetterberg, Kaj Blennow, Walter A Kukull, Kelley M Faber, Nicole Schupf, Maria C Norton, JoAnn Tschanz, Ronald G Munger, Christopher D Corcoran, Ekaterina Rogaeva, Chiao-Feng Lin, Beth A Dombroski, Laura B Cantwell, Amanda Partch, Otto Valladares, Hakon Hakonarson, Peter St George-Hyslop, Robert C Green, Alison M Goate, Tatiana M Foroud, Regina M Carney, Eric B Larson, Timothy W Behrens, John S Kauwe, Jonathan L Haines, Lindsay A Farrer, Margaret A Pericak-Vance, Richard Mayeux, Gerard D Schellenberg, Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Michael Barmada, Lisa Barnes, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, David A Bennett, Eileen H Bigio, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Steven L Carroll, Helena Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, F Yesim Demirci, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Nilufer Ertekin-Taner, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, Neill R Graff-Radford, John H Growdon, Ronald L Hamilton, Kara L Hamilton-Nelson, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Gregory A Jicha, Lee-Way Jin, Gyungah Jun, Gyungah Jun, M Ilyas Kamboh, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James Lah, James B Leverenz, Allan I Levey, Gei Li, Andrew P Lieberman, Oscar Lopez, Kathryn Lunetta, Constantine G Lyketsos, Wendy J Mack, Daniel C Marson, Eden R Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan McCurry, Andrew N McDavid, Ann C McKee, W Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, John C Morris, Jill R Murrell, John M Olichney, Joseph E Parisi, William Perry, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon Schneider, William Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Debby W Tsuang, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, and Lei Yu

    JAMA Neurology 72(2):209 (2015) PMID 25531812 PMCID PMC4324097

    Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this varia...
  14. Extracellular RNAs: development as biomarkers of human disease.

    Journal of Extracellular Vesicles 4:27495 (2015) PMID 26320940 PMCID PMC4553262

    Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and...
  15. Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction.

    Journal of Alzheimer's Disease 45(3):933 (2015) PMID 25633675 PMCID PMC4412033

    We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-β (Aβ)-induced cognitive deficits in vivo, and prevents Aβ-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown. The goal of this study was to identify bioche...
  16. Increased CSF E-Selectin in Clinical Alzheimer's Disease without Altered CSF Aβ42 and Tau.

    Journal of Alzheimer's Disease 47(4):883 (2015) PMID 26401768

    Clinically diagnosed Alzheimer's disease (AD) is pathologically heterogeneous. In this multicenter cohort of 215 clinically diagnosed AD patients and 249 controls, E-selectin and vascular cell adhesion molecule 1 (VACM-1) were measured along with amyloid-β peptide 1-42 (Aβ42) and tau. We discove...
  17. Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer's Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer's Disease.

    Journal of Alzheimer's Disease 48(2):537 (2015) PMID 26402017 PMCID PMC4713833

    Previous studies have demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of Alzheimer's disease (AD) patients. We extended these findings from non-targeted lipidomics studies to design a lipidomics platform to interrogate DAGs and monoacylglycerols (MAG) in t...
  18. Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.
    Adam C Naj, Gyungah Jun, Christiane Reitz, Brian W Kunkle, William Perry, Yo Son Park, Gary W Beecham, Ruchita A Rajbhandary, Kara L Hamilton-Nelson, Li-San Wang, John S Kauwe, Matthew J Huentelman, Amanda J Myers, Thomas D Bird, Bradley F Boeve, Clinton T Baldwin, Gail P Jarvik, Paul K Crane, Ekaterina Rogaeva, Michael Barmada, F Yesim Demirci, Carlos Cruchaga, Patricia L Kramer, Nilufer Ertekin-Taner, John Hardy, Neill R Graff-Radford, Robert C Green, Eric B Larson, Peter H St George-Hyslop, Joseph D Buxbaum, Denis A Evans, Julie A Schneider, Kathryn Lunetta, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, Philip L De Jager, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Eden R Martin, Jonathan L Haines, Richard P Mayeux, Lindsay A Farrer, Gerard D Schellenberg, Margaret A Pericak-Vance, Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Lisa Barnes, Thomas G Beach, James T Becker, Duane Beekly, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Chris S Carlson, Regina M Carney, Minerva Carrasquillo, Steven L Carroll, Helena Chui, David G Clark, Jason Corneveaux, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Chiao-Feng Lin, Oscar Lopez, Constantine G Lyketsos, Wendy J Mack, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Jill R Murrell, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Lon Schneider, William Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Otto Valladares, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, and Lei Yu

    JAMA Neurology 71(11):1394 (2014) PMID 25199842 PMCID PMC4314944

    Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. To investigate the effects of known Alzheimer disease risk lo...
  19. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease.

    JAMA Neurology 71(11):1405 (2014) PMID 25178429 PMCID PMC4227942

    Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understandi...
  20. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease.

    Acta Neuropathologica 128(5):639 (2014) PMID 24997849 PMCID PMC4201967

    Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, ...