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Brainstem damage is associated with poorer sleep quality and increased pain in gulf war illness veterans
Zhang, Yu; Vakhtin, Andrei A; Dietch, Jessica; Jennings, Jennifer S; Yesavage, Jerome A; Clark, J David; Bayley, Peter J; Ashford, J Wesson; Furst, Ansgar J
AIMS/OBJECTIVE:Gulf War Illness (GWI) is manifested as multiple chronic symptoms, including chronic pain, chronic fatigue, sleep problems, neuropsychiatric disorders, respiratory, gastrointestinal, and skin problems. No single target tissue or unifying pathogenic process has been identified that accounts for this variety of symptoms. The brainstem has been suspected to contribute to this multiple symptomatology. The aim of this study was to assess the role of the brainstem in chronic sleep problems and pain in GWI veterans. MATERIALS AND METHODS/METHODS:We enrolled 90 veterans (Age = 50 ± 5, 87% Male) who were deployed to the 1990-91 Gulf War and presented with GWI symptoms. Sleep quality was evaluated using the global Pittsburgh Sleep Quality Index. Pain intensities were obtained with the Brief Pain Inventory sum score. Volumes in cortical, subcortical, brainstem, and brainstem subregions and diffusion tensor metrics in 10 bilateral brainstem tracts were tested for correlations with symptom measures. KEY FINDINGS/RESULTS:Poorer sleep quality was significantly correlated with atrophy of the whole brainstem and brainstem subregions (including midbrain, pons, medulla). Poorer sleep quality also significantly correlated with lower fractional anisotropy in the nigrostriatal tract, medial forebrain tract, and the dorsal longitudinal fasciculus. There was a significant correlation between increased pain intensity and decreased fractional anisotropy in the dorsal longitudinal fasciculus. These correlations were not altered after controlling for age, sex, total intracranial volumes, or additional factors, e.g., depression and neurological conditions. SIGNIFICANCE/CONCLUSIONS:These findings suggest that the brainstem plays an important role in the aberrant neuromodulation of sleep and pain symptoms in GWI.
PMID: 34144059
ISSN: 1879-0631
CID: 4917832
Posttraumatic Stress Disorder-Associated Cognitive Deficits on the Repeatable Battery for the Assessment of Neuropsychological Status in a Veteran Population
Hantke, Nathan; Adamson, Maheen M; Noda, Art; Lazzeroni, Laura C; Beaudreau, Sherry A; Yutsis, Maya; Fairchild, J Kaci; Kinoshita, Lisa M; Kong, Jennifer; Sheng, Tong; Waltzman, Dana; Ashford, John Wesson; Yesavage, Jerome A
Background/UNASSIGNED:Posttraumatic stress disorder (PTSD) is a frequent problem of veterans receiving care and is often associated with cognitive deficits. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well-validated cognitive screening measure often used in the US Department of Veterans Affairs (VA), particularly in neurorehabilitation settings. However, the influence of PTSD on RBANS performance is unclear, particularly within a heterogeneous VA outpatient population in which PTSD and traumatic brain injury (TBI) may not be the primary focus of care. Methods/UNASSIGNED:Participants included 153 veterans with complex deployment-related health problems, including a diagnosis of PTSD (n = 98) and a history of TBI (n = 92). All veterans completed a targeted cognitive battery that included the Wechsler Test of Adult Reading, the Wechsler Adults Intelligence Scale, measure assessing processing speed, attention, and cognitive flexibility, and RBANS. Results/UNASSIGNED:A diagnosis of PTSD was associated with worse performance on the Story Recall subtest of the RBANS, but not on any other cognitive measures. A diagnosis of mild TBI, or co-occurring PTSD and TBI did not predict cognitive performance on any measures. Conclusions/UNASSIGNED:The RBANS best captured cognitive deficits associated with PTSD compared with a history of mild TBI or co-occurring mild TBI and PTSD. These findings may provide insight into the interpretation and attribution of cognitive deficits in the veteran population.
PMCID:7870275
PMID: 33574646
ISSN: 1078-4497
CID: 4780082
Brain health registry GenePool study: A novel approach to online genetics research
Fockler, Juliet; Kwang, Winnie; Ashford, Miriam T; Flenniken, Derek; Hwang, Joshua; Truran, Diana; Mackin, R Scott; Jin, Chengshi; O'Hara, Ruth; Hallmayer, Joachim F; Yesavage, Jerome A; Weiner, Michael W; Nosheny, Rachel L
Introduction/UNASSIGNED:Remote data collection, including the establishment of online registries, is a novel approach to efficiently identify risk for cognitive decline and Alzheimer's disease (AD) in older adults, with growing evidence for feasibility and validity. Addition of genetic data to online registries has the potential to facilitate identification of older adults at risk and to advance the understanding of genetic contributions to AD. Methods/UNASSIGNED:573 older adult participants with longitudinal online Brain Health Registry (BHR) data underwent apolipoprotein E (APOE) genotyping using remotely collected saliva samples and a novel, automated Biofluid Collection Management Portal. We evaluated acceptability of genetic sample collection and estimated associations between (1) sociodemographic variables and willingness to participate in genetics research and (2) APOE results and online cognitive and functional assessments. We also assessed acceptance of hypothetical genetics research participation by surveying a larger sample of 25,888 BHR participants. Results/UNASSIGNED:51% of invited participants enrolled in the BHR genetics study, BHR-GenePool Study (BHR-GPS); 27% of participants had at least one APOE ε4 allele. Older participants and those with higher educational attainment were more likely to participate. In the remotely administered Cogstate Brief Battery, APOE ε4/ε4 homozygotes (HM) had worse online learning scores, and greater decline in processing speed and attention, compared to ε3/ε4 heterozygotes (HT) and ε4 non-carriers (NC). Discussion/UNASSIGNED:APOE genotyping of more than 500 older adults enrolled in BHR supports the feasibility and validity of a novel, remote biofluids collection approach from a large cohort of older adults, with data linkage to longitudinal online cognitive data. This approach can be expanded for efficient collection of genetic data and other information from biofluids in the future.
PMCID:7882536
PMID: 33614891
ISSN: 2352-8737
CID: 4794162
A Clinical Program to Implement Repetitive Transcranial Magnetic Stimulation for Depression in the Department of Veterans Affairs
Carrico, Whitney T; Georgette, Gerald; Madore, Michelle R; Kozel, F Andrew; George, Mark S; Lindley, Steven; Lovett, Steven; Yoon, Jong H; Yesavage, Jerome A
Background/UNASSIGNED:Repetitive transcranial magnetic stimulation (rTMS) uses a device to create magnetic fields that cause electrical current to flow into targeted neurons in the brain. The most common clinical use of rTMS is for the treatment of major depressive disorder (MDD). The annual suicide rate of veterans has been higher than the national average; treating depression with rTMS would likely decrease suicide risk. MDD in many patients can be chronic and reoccurring with medication and psychotherapy providing inadequate relief. Methods/UNASSIGNED:A pilot program was created to supply rTMS devices to 35 different sites in the VA nationwide in order to treat treatment-resistant depression. Conclusions/UNASSIGNED:At time of analysis more than 950 veterans have started the program and 412 have finished. Nationwide, we have seen the depression scores decline, indicating an improvement in well-being. In addition, there is high patient satisfaction. Collecting data on a national level is a powerful way to examine rTMS efficacy and predictors of response which might be lost on a smaller subset of cases.
PMCID:7357884
PMID: 32669780
ISSN: 1078-4497
CID: 4528282
FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease
Yan, Tingxiang; Liang, Jingjing; Gao, Ju; Wang, Luwen; Fujioka, Hisashi; Zhu, Xiaofeng; Wang, Xinglong; Weiner, Michael W; Schuff, Norbert; Rosen, Howard J; Miller, Bruce L; Perry, David; Aisen, Paul; Toga, Arthur W; Jimenez, Gustavo; Donohue, Michael; Gessert, Devon; Harless, Kelly; Salazar, Jennifer; Cabrera, Yuliana; Walter, Sarah; Hergesheimer, Lindsey; Toga, Arthur W; Crawford, Karen; Neu, Scott; Schneider, Lon S; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; Spann, Bryan M; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S; Albers, Colleen S; Knopman, David; Johnson, Kris; Graff-Radford, Neill R; Parfitt, Francine; Poki-Walker, Kim; Jagust, William; Landau, Susan; Trojanowki, John Q; Shaw, Leslie M; Karlawish, Jason H; Wolk, David A; Vaishnavi, Sanjeev; Clark, Christopher M; Arnold, Steven E; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Beckett, Laurel; Harvey, Danielle; DeCArli, Charles; Fletcher, Evan; Maillard, Pauline; Olichney, John; Carmichael, Owen; Green, Robert C; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad A; Saykin, Andrew J; Foroud, Tatiana M; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Brosch, Jared R; Herring, Scott; Morris, John; Raichle, Marc; Holtzman, David; Morris, John C; Cairns, Nigel J; Franklin, Erin; Taylor-Reinwald, Lisa; Ances, Beau; Winkfield, David; Carroll, Maria; Oliver, Angela; Creech, Mary L; Mintun, Mark A; Schneider, Stacy; Kuller, Lew; Mathis, Chet; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Paul, Steven; Relkin, Norman; Chiang, Gloria; Lin, Michael; Ravdin, Lisa; Davies, Peter; Mesulam, M Marcel; Mesulam, Marek-Marsel; Rogalski, Emily; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Snyder, Peter J; Montine, Tom; Donohue, Michael; Thal, Lean; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Thompson, Paul; Woo, Ellen; Silverman, Daniel H S; Teng, Edmond; Kremen, Sarah; Apostolova, Liana; Tingus, Kathleen; Lu, Po H; Bartzokis, George; Koeppe, Robert A; Ziolkowski, Jaimie; Heidebrink, Judith L; Lord, Joanne L; Foster, Norm; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Quinn, Joseph; Silbert, Lisa C; Lind, Betty; Kaye, Jeffrey A; Carter, Raina; Dolen, Sara; Villanueva-Meyer, Javier; Pavlik, Valory; Pacini, Nathaniel; Lamb, Ashley; Kass, Joseph S; Doody, Rachelle S; Shibley, Victoria; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Yeh, Randy; Marson, Daniel; Geldmacher, David; Natelson, Marissa; Griffith, Randall; Clark, David; Brockington, John; Grossman, Hillel; Mitsis, Effie; Shah, Raj C; Lamar, Melissa; Samuels, Patricia; Sadowski, Martin; Sheikh, Mohammed O; Singleton-Garvin, Jamika; Ulysse, Anaztasia; Gaikwad, Mrunalini; Doraiswamy, P Murali; James, Olga; Borges-Neto, Salvador; Wong, Terence Z; Coleman, Edward; Smith, Charles D; Jicha, Greg; Hardy, Peter; El Khouli, Riham; Oates, Elizabeth; Conrad, Gary; Porsteinsson, Anton P; Martin, Kim; Kowalksi, Nancy; Keltz, Melanie; Goldstein, Bonnie S; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Thai, Gaby; Pierce, Aimee; Yanez, Beatriz; Sosa, Elizabeth; Witbracht, Megan; Potkin, Steven; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Swerdlow, Russell H; Brooks, William M; van Dyck, Christopher H; Carson, Richard E; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Oyonumo, Ntekim E; Allard, Joanne; Ogunlana, Olu; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M; Yesavage, Jerome; Taylor, Joy L; Chao, Steven; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Scharre, Douglas W; Kataki, Maria; Tarawneh, Rawan; Zimmerman, Earl A; Celmins, Dzintra; Hart, David; Flashman, Laura A; Seltzer, Marc; Hynes, Mary L; Santulli, Robert B; Sink, Kaycee M; Yang, Mia; Mintz, Akiva; Miller, Delwyn D; Smith, Karen Ekstam; Koleva, Hristina; Nam, Ki Won; Shim, Hyungsub; Schultz, Susan K; Smith, Amanda; Leach, Christi; Raj, Balebail Ashok; Fargher, Kristin; Reiman, Eric M; Chen, Kewei; Tariot, Pierre; Burke, Anna; Hetelle, Joel; DeMarco, Kathryn; Trncic, Nadira; Fleisher, Adam; Reeder, Stephanie; Zamrini, Edward; Belden, Christine M; Sirrel, Sherye A; Duara, Ranjan; Greig-Custo, Maria T; Rodriguez, Rosemarie; Bernick, Charles; Munic, Donna; Khachaturian, Zaven; Buckholtz, Neil; Hsiao, John; Potter, William; Fillit, Howard; Hefti, Franz; Sadowsky, Carl; Villena, Teresa; Hsiung, Ging-Yuek Robin; Mudge, Benita; Sossi, Vesna; Feldman, Howard; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Pavlosky, William; Rachinsky, Irina; Drost, Dick; Kertesz, Andrew; Black, Sandra; Stefanovic, Bojana; Heyn, Chrinthaka; Ott, Brian R; Tremont, Geoffrey; Daniello, Lori A; Bodge, Courtney; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Lee, Athena; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabeth; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick; Finger, Elizabeth; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Frank, Richard; Fox, Nick; Logovinsky, Veronika; Corrillo, Maria; Sorensen, Greg
Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.
PMCID:6972869
PMID: 31964863
ISSN: 2041-1723
CID: 5134432
Sleep-wake disorders in Alzheimer's disease: further genetic analyses in relation to objective sleep measures
Yesavage, Jerome A; Noda, Art; Heath, Alesha; McNerney, M Windy; Domingue, Benjamin W; Hernandez, Yozen; Benson, Gary; Hallmayer, Joachim; O'Hara, Ruth; Williams, Leanne M; Goldstein-Piekarski, Andrea N; Zeitzer, Jamie M; Fairchild, J Kaci
This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
PMID: 31739820
ISSN: 1741-203x
CID: 4208682
Multimodal Hippocampal Subfield Grading For Alzheimer's Disease Classification
Hett, Kilian; Vinh-Thong Ta; Catheline, Gwenaelle; Tourdias, Thomas; Manjon, Jose V.; Coupe, Pierrick; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulam, M. Marcel; Potter, William; Snyder, Peter; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Decarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Lean; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Love, Marissa Natelson; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Grossman, Hillel; Mitsis, Effie; Shah, Raj C.; deToledo-Morrell, Leyla; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Albert, Marilyn; Onyike, Chiadi; D\Agostino, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Borges-Neto, Salvador; Wong, Terence Z.; Coleman, Edward; Levey, Allan I.; Lah, James J.; Cella, Janet S.; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Graff-Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Rachisky, Irina; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Lipowski, Kristine; Weintraub, M. A. Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Burke, Anna; Trncic, Nadira; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Ponto, Laura L. Boles; Shim, Hyungsub; Smith, Karen Ekstam; Relkin, Norman; Chaing, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Raj, Balebail Ashok; Fargher, Kristin
ISI:000487586600036
ISSN: 2045-2322
CID: 4155602
Sex Differences in the Neuropsychiatric Symptoms of Patients With Alzheimer's Disease
Tao, Ye; Peters, Matthew E; Drye, Lea T; Devanand, Davangere P; Mintzer, Jacobo E; Pollock, Bruce G; Porsteinsson, Anton P; Rosenberg, Paul B; Schneider, Lon S; Shade, David M; Weintraub, Daniel; Yesavage, Jerome; Lyketsos, Constantine G; Munro, Cynthia A
The aim of this study was to describe sex differences in neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD). Baseline scores on the Cohen-Mansfield Agitation Inventory, Neurobehavioral Rating Scale-Agitation subscale, and the Neuropsychiatric Inventory from patients with AD enrolled in a multicenter trial of citalopram for the treatment of agitation were analyzed. We found not only that patients with AD having agitation were likely to exhibit many other NPSs but also that the women in this study were more likely to exhibit a broader range of NPS than were the men. These results suggest greater heterogeneity in the clinical presentation of women compared to men, and thus in the potential targets for treatment in these patients. Further characterization of sex differences in NPS can inform future efforts aimed at establishing subtypes of patients for whom various treatment approaches will be most appropriate.
PMID: 29969907
ISSN: 1938-2731
CID: 3371932
Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: A Randomized Clinical Trial
Yesavage, Jerome A; Fairchild, J Kaci; Mi, Zhibao; Biswas, Kousick; Davis-Karim, Anne; Phibbs, Ciaran S; Forman, Steven D; Thase, Michael; Williams, Leanne M; Etkin, Amit; O'Hara, Ruth; Georgette, Gerald; Beale, Tamara; Huang, Grant D; Noda, Art; George, Mark S
Importance/UNASSIGNED:Treatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans. Objective/UNASSIGNED:To determine the efficacy of rTMS in the treatment of TRMD in veterans. Design, Setting, and Participants/UNASSIGNED:A double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated. Interventions/UNASSIGNED:Participants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions. Main Outcomes and Measures/UNASSIGNED:The primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ≤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life. Results/UNASSIGNED:The 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission. Conclusions and Relevance/UNASSIGNED:A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01191333.
PMID: 29955803
ISSN: 2168-6238
CID: 3168692
18F-florbetapir Positron Emission Tomography-determined Cerebral beta-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery
Klinger, Rebecca Y; James, Olga G; Borges-Neto, Salvador; Bisanar, Tiffany; Li, Yi-Ju; Qi, Wenjing; Berger, Miles; Terrando, Niccola; Newman, Mark F; Doraiswamy, P Murali; Mathew, Joseph P; Weiner, Michael W; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J;Shaw, Leslie M; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, David; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B; Mason, Jennifer; Sim, Iris; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCArli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Landau, Susan; Morris, John C; Cairns, Louis Nigel J; Franklin, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Lean; Thal, Leon; Buckholtz, Neil; Snyder, Peter J; Albert, Marilyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Becerra, Mauricio; Teodoro, Liberty; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L; Lord, Joanne L; Mason, Sara S; Albers, Colleen S; Knopman, David; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Pavlik, Valory; Shibley, Victoria; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Ances, Beau; Carroll, Maria; Creech, Mary L; Mintun, Mark A; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Geldmacher, David; Love, Marissa Natelson; Griffith, Randall; Clark, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; Shah, Raj C; deToledo-Morrell, Leyla; Duara, Ranjan; Greig-Custo, Maria T; Barker, Warren; Onyike, Chiadi; D'Agostino, Daniel; Kielb, Stephanie; Sadowski, Martin; Sheikh, Mohammed O; Ulysse, Anaztasia; Gaikwad, Mrunalini; Petrella, Jeffrey R; Wong, Terence Z; Coleman, Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David A; Clark, Christopher M; Smith, Charles D; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Swerdlow, Russell H; Brooks, William M; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H S; Lu, Po H; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Poki-Walker, Kim; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Brosch, Jared R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Varma, Pradeep; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Robin; Mudge, Benita; Sossi, Vesna; Feldman, Howard; Assaly, Michele; Finger, Elizabeth; Pasternack, Stephen; Trost, Dick; Kertesz, Andrew; Bernick, Charles; Munic, Donna; Mesulam, Marek-Marsel; Rogalski, Emily; Lipowski, Kristine; Weintraub, Sandra; Bonakdarpour, Borna; Kerwin, Diana; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N; Belden, Christine M; Jacobson, Sandra A; Sirrel, Sherye A; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Fletcher, Evan; Maillard, Pauline; Olichney, John; DeCarli, Charles; Carmichael, Owen; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Dr Rob; Asthana, Sanjay; Carlsson, Cynthia M; Tariot, Pierre; Burke, Anna; Milliken, Ann Marie; Trncic, Nadira; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Kelley, Brendan; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Flashman, Laura A; Seltzer, Marc; Hynes, Mary L; Santulli, Robert B; Sink, Kaycee M; Gordineer, Leslie; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Tremont, Geoffrey; Daiello, Lori A; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Perry, David; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Rachinsky, Irina; Rogers, John; Drost, Dick; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K; Smith, Karen Ekstam; Koleva, Hristina; Nam, Ki Won; Shim, Hyungsub; Relkin, Norman; Chiang, Gloria; Lin, Michael; Ravdin, Lisa; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Neylan, Thomas; Grafman, Jordan; Thomas, Ronald G; Davis, Melissa; Morrison, Rosemary; Hayes, Jacqueline; Finely, Shannon; Cairns, Nigel J; Householder, Erin; Crawford, Karen; Friedl, Karl; Fleischman, Debra; Arfanakis, Konstantinos; Varon, Daniel; Greig, Maria T; Martin, Kimberly S; Preda, Adrian; Massoglia, Dino; Brawman-Mintzer, Olga; Martinez, Walter; Behan, Kelly; Johnson, Sterling C; Fruehling, J Jay; Harding, Sandra; Peskind, Elaine R; Petrie, Eric C; Li, Gail; Furst, Ansgar J; Chao, Steven; Blumenthal, James A; Karhausen, Jorn A; Kertai, Miklos D; Podgoreanu, Mihai V; Stafford-Smith, Mark; Swaminathan, Madhav; Warner, David S; Funk, Bonita L; Balajonda, Narai; Brassard, Rachele; Cooter, Mary; Toulgoat-Dubois, Yanne; Waweru, Peter; Babyak, Michael A; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A; Sketch, Michael H; Bennett, Ellen R; Graffagnino, Carmelo; Laskowitz, Daniel T; Strittmatter, Warren J; Collins, Kevin; Smigla, Greg; Shearer, Ian; D'Amico, Thomas A; Daneshmand, Mani A; Gaca, R Jeffrey G; Glower, Donald D; Haney, Jack; Harpole, R David; Hartwig, Mathew G; Hughes, G Chad; Klapper, Jacob A; Lin, Shu S; Lodge, Andrew J; Milano, Carmelo A; Plichta, Ryan P; Schroeder, Jacob N; Smith, Peter K; Tong, Betty C
BACKGROUND:Amyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively. METHODS:Amyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype. RESULTS:The authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls. CONCLUSIONS:In this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.
PMCID:5849499
PMID: 29389750
ISSN: 1528-1175
CID: 2994312
