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2. Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish

Author

Osterman, Michael D., Song, Yeunjoo E., Lynn, Audrey, Miskimen, Kristy, Adams, Larry D., Laux, Renee A., Caywood, Laura J., Prough, Michael B., Clouse, Jason E., Herington, Sharlene D., Slifer, Susan H., Fuzzell, Sarada L., Hochstetler, Sherri D., Main, Leighanne R., Dorfsman, Daniel A., Zaman, Andrew F., Ogrocki, Paula, Lerner, Alan J., Vance, Jeffery M., Cuccaro, Michael L., Scott, William K., Pericak-Vance, Margaret A., and Haines, Jonathan L.

Published
2023
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4. Visuospatial and Verbal Memory Differences in Amish Individuals with Alzheimer Disease and Related Dementias

Author

Prough, Michael B., Zaman, Andrew, Caywood, Laura J., Clouse, Jason E., Herington, Sharlene D., Slifer, Susan H., Dorfsman, Daniel A., Adams, Larry A., Laux, Reneé A., Song, Yeunjoo E., Lynn, Audrey, Fuzzell, Denise, Fuzzell, Sarada L., Miller, Sherri D., Miskimen, Kristy, Main, Leighanne R., Osterman, Michael D., Ogrocki, Paula, Lerner, Alan J., Vance, Jeffery M., Haines, Jonathan L., Scott, William K., Pericak-Vance, Margaret, and Cuccaro, Michael L.

Published
2023
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5. Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.

Author

Tumati, Shankar, Herrmann, Nathan, Perin, Jaime, Rosenberg, Paul B., Lerner, Alan J., Mintzer, Jacobo, Padala, Prasad R., Brawman-Mintzer, Olga, van Dyck, Christopher H., Porsteinsson, Anton P., Craft, Suzanne, Levey, Allan, Shade, David, and Lanctôt, Krista L.

Abstract

Objectives: Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. Design: Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. Setting: Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively. Participants: Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease. Measurements: The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory – Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics. Results: Among the MCID was a decrease of four points (95% CI: −4.0 to −4.8) on the NPI-A, 0.56 points (95% CI: −0.47 to −0.65) on the DAIR, and three points on the AES-I (95% CI: −0.9 to −5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID. Conclusions: MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.

Author

Main, Leighanne R., Song, Yeunjoo E., Lynn, Audrey, Laux, Renee A., Miskimen, Kristy L., Osterman, Michael D., Cuccaro, Michael L., Ogrocki, Paula K., Lerner, Alan J., Vance, Jeffery M., Fuzzell, Denise, Fuzzell, Sarada L., Hochstetler, Sherri D., Dorfsman, Daniel A., Caywood, Laura J., Prough, Michael B., Adams, Larry D., Clouse, Jason E., Herington, Sharlene D., and Scott, William K.

Abstract

INTRODUCTION: Alzheimer's disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age. METHODS: Genome‐wide association and linkage analyses were performed on 946 examined and sampled Amish individuals, aged 76–95, who were either cognitively unimpaired (CU) or impaired (CI). RESULTS: A total of 12 single nucleotide polymorphisms (SNPs) demonstrated suggestive association (P ≤ 5 × 10−4) with cognitive preservation. Genetic linkage analyses identified > 100 significant (logarithm of the odds [LOD] ≥ 3.3) SNPs, some which overlapped with the association results. Only one locus on chromosome 2 retained significance across multiple analyses. DISCUSSION: A novel significant result for cognitive preservation on chromosome 2 includes the genes LRRTM4 and CTNNA2. Additionally, the lead SNP, rs1402906, impacts the POU3F2 transcription factor binding affinity, which regulates LRRTM4 and CTNNA2. Highlights: GWAS and linkage identified over 100 loci associated with cognitive preservation.One locus on Chromosome 2 retained significance over multiple analyses.Predicted TFBSs near rs1402906 regulate genes associated with neurocognition. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial)

Author

Zeng, Lijuan, primary, Perin, Jamie, additional, Gross, Alden L., additional, Shade, David, additional, Lanctôt, Krista L., additional, Lerner, Alan J., additional, Mintzer, Jacobo E., additional, Brawman‐Mintzer, Olga, additional, Padala, Prasad R., additional, van Dyck, Christopher H., additional, Porsteinsson, Anton P., additional, Craft, Suzanne, additional, Levey, Allan, additional, Herrmann, Nathan, additional, and Rosenberg, Paul B., additional

Published
2024
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12. Effects of intensive versus standard blood pressure control on domain-specific cognitive function: a substudy of the SPRINT randomised controlled trial

Author

Rapp, Stephen R, Pajewski, Nicholas M, Auchus, Alexander P, Chelune, Gordon, Cheung, Alfred K, Cleveland, Maryjo L, Coker, Laura H, Crowe, Michael G, Cushman, William C, Cutler, Jeffery A, Davatzikos, Christos, Desiderio, Lisa, Doshi, Jimit, Erus, Guray, Fine, Lawrence J, Gaussoin, Sarah A, Harris, Darrin, Johnson, Karen C, Kimmel, Paul L, Tamura, Manjula K, Launer, Lenore J, Lerner, Alan J, Lewis, Cora E, Martindale-Adams, Jennifer, Moy, Claudia S, Nichols, Linda O, Oparil, Suzanne, Ogrocki, Paula K, Rahman, Mahboob, Nasrallah, Ilya M, Reboussin, David M, Rocco, Michael V, Sachs, Bonnie C, Sink, Kaycee M, Still, Carolyn H, Supiano, Mark A, Snyder, Joni K, Wadley, Virginia G, Walker, Jennifer, Weiner, Daniel E, Whelton, Paul K, Wilson, Valerie M, Woolard, Nancy, Wright, Jackson T, Jr., Wright, Clinton B, Williamson, Jeff D, Bryan, R Nick, Wilson, Valarie M, Whittle, Jeff C, Beddhu, Srinivasan, Berlowitz, Dan R, Bress, Adam P, Krousel-Wood, Marie, Miller, Eliza C, Rifkin, Dena E, Tamariz, Leonardo, Wolfgram, Dawn F, Yang, Mia, and Bryan, Robert Nick

Published
2020
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14. Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN)

Author

Gore, Ethan, Appleby, Brian S, Cohen, Mark L, DeBrosse, Suzanne D, Leverenz, James B, Miller, Bruce L, Siedlak, Sandra L, Zhu, Xiongwei, and Lerner, Alan J

Subjects
Biological Psychology, Psychology, Neurodegenerative, Biomedical Imaging, Neurosciences, Clinical Research, Genetics, Brain Disorders, Aging, 4.2 Evaluation of markers and technologies, Aetiology, Detection, screening and diagnosis, 2.1 Biological and endogenous factors, Neurological, Mental health, Adult, Family Health, Genetic Testing, Humans, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Male, Mitochondrial Proteins, Mutation, Neurodegenerative Diseases, Positron-Emission Tomography, Mitochondrial membrane protein-associatedneurodegeneration, neurodegeneration with brain iron accumulation, Lewy body, Parkinsonism, whole exome sequencing, Clinical Sciences, Cognitive Sciences, Experimental Psychology, Biological psychology, Clinical and health psychology
Abstract

Young onset dementias present significant diagnostic challenges. We present the case of a 35-year-old Kuwaiti man with social withdrawal, drowsiness, irritability, anxiety, aphasia, memory loss, hypereflexia, and Parkinsonism. Brain MRI showed bilateral symmetric gradient echo hypointensities in the globi pallidi and substantiae nigrae. Left cortical hypometabolism was seen on brain fluorodeoxyglucose positron emission tomography. A cortical brain biopsy revealed a high Lewy body burden. Genetic testing revealed a homozygous p.T11M mutation in the C19orf12 gene consistent with mitochondrial membrane protein-associated neurodegeneration. This is the oldest onset age of MPAN reported.

Published
2016

15. Improving clinical cognitive testing

Author

Daffner, Kirk R, Gale, Seth A, Barrett, AM, Boeve, Bradley F, Chatterjee, Anjan, Coslett, H Branch, D'Esposito, Mark, Finney, Glen R, Gitelman, Darren R, Hart, John J, Lerner, Alan J, Meador, Kimford J, Pietras, Alison C, Voeller, Kytja S, and Kaufer, Daniel I

Subjects
Basic Behavioral and Social Science, Mental Health, Clinical Research, Mind and Body, Behavioral and Social Science, Neurosciences, Mental health, Adult, Behavior Rating Scale, Cognition Disorders, Female, Humans, Male, Middle Aged, Neurology, Neuropsychological Tests, Physicians, Research Report, Surveys and Questionnaires, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment.MethodsBehavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain.ResultsDemographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE.ConclusionsWe identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment.

Published
2015

18. Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F18]-T808

Author

Chien, David T, Szardenings, A Katrin, Bahri, Shadfar, Walsh, Joseph C, Mu, Fanrong, Xia, Chunfang, Shankle, William R, Lerner, Alan J, Su, Min-Ying, Elizarov, Arkadij, and Kolb, Hartmuth C

Subjects
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Neurodegenerative, Alzheimer's Disease Related Dementias (ADRD), Aging, Brain Disorders, Neurosciences, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Dementia, Biomedical Imaging, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Benzimidazoles, Brain, Brain Mapping, Female, Fluorodeoxyglucose F18, Humans, Male, Mental Status Schedule, Middle Aged, Positron-Emission Tomography, Pyrimidines, Time Factors, tau Proteins, Alzheimer's disease, amyloid-beta, brain imaging, mild cognitive impairment, molecular imaging, neurofibrillary tangles, PHF-tau, tau, tau aggregates, tauopathy, amyloid-β, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have recently reported early clinical results of a novel PHF-tau targeting PET imaging agent, [F18]-T807. Since then, we have investigated a second novel PHF-tau targeting PET imaging agent, [F18]-T808, with different pharmacokinetic characteristics, which may be favorable for imaging Alzheimer's disease and other tauopathies. Here, we describe the first human brain images with [F18]-T808.

Published
2014

19. Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2

Author

Main, Leighanne R, primary, Song, Yeunjoo E, additional, Lynn, Audrey, additional, Laux, Renee A, additional, Miskimen, Kristy L, additional, Osterman, Michael D, additional, Cuccaro, Michael L, additional, Ogrocki, Paula K, additional, Lerner, Alan J, additional, Vance, Jeffery M, additional, Fuzzell, M Denise, additional, Fuzzell, Sarada L, additional, Hochstetler, Sherri D, additional, Dorfsman, Daniel A, additional, Caywood, Laura J, additional, Prough, Michael B, additional, Adams, Larry D, additional, Clouse, Jason E, additional, Herington, Sharlene D, additional, Scott, William K, additional, Pericak-Vance, Margaret A, additional, and Haines, Jonathan L, additional

Published
2023
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24. Detecting Protective Rare Variants for Alzheimer’s Disease from Whole‐Genome Sequencing in the Amish

Author

Song, Yeunjoo E., primary, Wang, Weihuan, additional, Miskimen, Kristy L., additional, Laux, Renee A., additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Hochstetler, Sherri D., additional, Main, Leighanne R., additional, Osterman, Michael D., additional, Lynn, Audrey, additional, Prough, Michael B., additional, Slifer, Susan H., additional, Adams, Larry D., additional, Caywood, Laura J., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Dorfsman, Daniel A., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Scott, William K., additional, Pericak‐Vance, Margaret A., additional, and Haines, Jonathan L., additional

Published
2023
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25. The Genetics of Cognitive Resistance and Resilience in the Ohio and Indiana Amish

Author

Main, Leighanne R., primary, Song, Yeunjoo E., additional, Laux, Renee A., additional, Miskimen, Kristy L., additional, Cuccaro, Michael L., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Vance, Jeffery M., additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Hochstetler, Sherri D., additional, Osterman, Michael D., additional, Lynn, Audrey, additional, Dorfsman, Daniel A., additional, Caywood, Laura J., additional, Prough, Michael B., additional, Adams, Larry D., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Scott, William K., additional, Pericak‐Vance, Margaret A., additional, and Haines, Jonathan L., additional

Published
2023
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27. Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial

Author

Tumati, Shankar, primary, Vieira, Danielle, additional, Bawa, Kritleen Kaur, additional, Andreazza, Ana C., additional, Mintzer, Jacobo, additional, Scherer, Roberta, additional, Rosenberg, Paul B., additional, van Dyck, Christopher H, additional, Padala, Prasad R, additional, Brawman‐Mintzer, Olga, additional, Porsteinsson, Anton P., additional, Lerner, Alan J., additional, Craft, Suzanne, additional, Levey, Allan I., additional, Burke, William J, additional, Perin, Jamie, additional, Shade, David, additional, Herrmann, Nathan, additional, and Lanctôt, Krista L., additional

Published
2023
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31. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry

Author

Katsumata, Yuriko, primary, Fardo, David W, additional, Shade, Lincoln M P, additional, Bowen, James D, additional, Crane, Paul K, additional, Jarvik, Gail P, additional, Keene, C Dirk, additional, Larson, Eric B, additional, McCormick, Wayne C, additional, McCurry, Susan M, additional, Mukherjee, Shubhabrata, additional, Kowall, Neil W, additional, McKee, Ann C, additional, Honig, Robert A, additional, Lawrence, S, additional, Vonsattel, Jean Paul, additional, Williamson, Jennifer, additional, Small, Scott, additional, Burke, James R, additional, Hulette, Christine M, additional, Welsh-Bohmer, Kathleen A, additional, Gearing, Marla, additional, Lah, James J, additional, Levey, Allan I, additional, Wingo, Thomas S, additional, Apostolova, Liana G, additional, Farlow, Martin R, additional, Ghetti, Bernardino, additional, Saykin, Andrew J, additional, Spina, Salvatore, additional, Albert, Marilyn S, additional, Lyketsos, Constantine G, additional, Troncoso, Juan C, additional, Frosch, Matthew P, additional, Green, Robert C, additional, Growdon, John H, additional, Hyman, Bradley T, additional, Tanzi, Rudolph E, additional, Potter, Huntington, additional, Dickson, Dennis W, additional, Ertekin-Taner, Nilufer, additional, Graff-Radford, Neill R, additional, Parisi, Joseph E, additional, Petersen, Ronald C, additional, Duara, Ranjan, additional, Buxbaum, Joseph D, additional, Goate, Alison M, additional, Sano, Mary, additional, Masurkar, Arjun V, additional, Wisniewski, Thomas, additional, Bigio, Eileen H, additional, Mesulam, Marsel, additional, Weintraub, Sandra, additional, Vassar, Robert, additional, Kaye, Jeffrey A, additional, Quinn, Joseph F, additional, Woltjer, Randall L, additional, Barnes, Lisa L, additional, Bennett, David A, additional, Schneider, Julie A, additional, Yu, Lei, additional, Henderson, Victor, additional, Fallon, Kenneth B, additional, Harrell, Lindy E, additional, Marson, Daniel C, additional, Roberson, Erik D, additional, DeCarli, Charles, additional, Jin, Lee-Way, additional, Olichney, John M, additional, Kim, Ronald, additional, LaFerla, Frank M, additional, Monuki, Edwin, additional, Head, Elizabeth, additional, Sultzer, David, additional, Geschwind, Daniel H, additional, Vinters, Harry V, additional, Chesselet, Marie-Francoise, additional, Galasko, Douglas R, additional, Brewer, James B, additional, Boxer, Adam, additional, Karydas, Anna, additional, Kramer, Joel H, additional, Miller, Bruce L, additional, Rosen, Howard J, additional, Seeley, William W, additional, Burns, Jeffrey M, additional, Swerdlow, Russell H, additional, Abner, Erin, additional, Van Eldik, Linda J, additional, Albin, Roger L, additional, Lieberman, Andrew P, additional, Paulson, Henry L, additional, Arnold, Steven E, additional, Trojanowski, John Q, additional, Van Deerlin, Vivianna M, additional, Hamilton, Ronald L, additional, Kamboh, M Ilyas, additional, Lopez, Oscar L, additional, Becker, James T, additional, Cao, Chuanhai, additional, Raj, Ashok, additional, Smith, Amanda G, additional, Chui, Helena C, additional, Miller, Carol A, additional, Ringman, John M, additional, Schneider, Lon S, additional, Bird, Thomas D, additional, Sonnen, Joshua A, additional, Yu, Chang-En, additional, Grabowski, Thomas, additional, Peskind, Elaine, additional, Raskind, Murray, additional, Li, Ge, additional, Tsuang, Debby W, additional, Asthana, Sanjay, additional, Atwood, Craig S, additional, Carlsson, Cynthia M, additional, Sager, Mark A, additional, Chin, Nathaniel A, additional, Craft, Suzanne, additional, Cairns, Nigel J, additional, Morris, John C, additional, Cruchaga, Carlos, additional, Strittmatter, Stephen, additional, Reiman, Eric M, additional, Beach, Thomas G, additional, Huentelman, Matthew J, additional, Hardy, John, additional, Myers, Amanda J, additional, Kauwe, John S K, additional, Hakonarson, Hakon, additional, Blacker, Deborah, additional, Montine, Thomas J, additional, Baldwin, Clinton T, additional, Farrer, Lindsay A, additional, Jun, Gyungah, additional, Lunetta, Kathryn L, additional, Bush, William S, additional, Haines, Jonathan L, additional, Lerner, Alan J, additional, Zhou, Xiongwei, additional, Barral, Sandra, additional, Reitz, Christiane, additional, Vardarajan, Badri N, additional, Mayeux, Richard, additional, Beecham, Gary W, additional, Carney, Regina M, additional, Cuccaro, Michael L, additional, Gilbert, John R, additional, Hamilton-Nelson, Kara L, additional, Kunkle, Brian W, additional, Martin, Eden R, additional, Pericak-Vance, Margaret A, additional, Vance, Jeffery M, additional, Cantwell, Laura B, additional, Kuzma, Amanda P, additional, Malamon, John, additional, Naj, Adam C, additional, Qu, Liming, additional, Schellenberg, Gerard D, additional, Valladares, Otto, additional, Wang, Li-San, additional, Zhao, Yi, additional, Leverenz, James B, additional, De Jager, Philip L, additional, Evans, Denis A, additional, Katz, Mindy J, additional, Lipton, Richard B, additional, Boeve, Bradley F, additional, Allen, Mariet, additional, Carrasquillo, Minerva M, additional, Younkin, Steven G, additional, Kukull, Walter A, additional, Faber, Kelley M, additional, Foroud, Tatiana M, additional, Pavlik, Valory, additional, Massman, Paul, additional, Darby, Eveleen, additional, Rodriguear, Monica, additional, Khaleeq, Aisha, additional, Royall, Donald R, additional, Stevens, Alan, additional, Ory, Marcia, additional, DeToledo, John C, additional, Wilms, Henrick, additional, Johnson, Kim, additional, Perez, Victoria, additional, Hernandez, Michelle, additional, Wilhelmsen, Kirk C, additional, Tilson, Jeffrey, additional, Chasse, Scott, additional, Barber, Robert C, additional, Fairchild, Thomas J, additional, O’Bryant, Sid E, additional, Knebl, Janice, additional, Hall, James R, additional, Johnson, Leigh, additional, Mains, Douglas, additional, Alvarez, Lisa, additional, Gamboa, Adriana, additional, Paydarfar, David, additional, Bertelson, John, additional, Woon, Martin, additional, Ayres, Gayle, additional, Aguirre, Alyssa, additional, Palmer, Raymond, additional, Polk, Marsha, additional, Adams, Perrie M, additional, Huebinger, Ryan M, additional, Reisch, Joan S, additional, Rosenberg, Roger N, additional, Cullum, Munro, additional, Williams, Benjamin, additional, Quiceno, Mary, additional, Hynan, Linda, additional, Smith, Janet, additional, Davis, Barb, additional, Nguyen, Trung, additional, Rogaeva, Ekaterina, additional, George-Hyslop, Peter St, additional, and Nelson, Peter T, additional

Published
2023
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34. Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2)

Author

Lanctôt, Krista L., primary, Chen, Clara, additional, Mah, Ethan, additional, Kiss, Alex, additional, Li, Abby, additional, Shade, Dave, additional, Scherer, Roberta W., additional, Vieira, Danielle, additional, Coulibaly, Hamadou, additional, Rosenberg, Paul B., additional, Lerner, Alan J., additional, Padala, Prasad R., additional, Brawman-Mintzer, Olga, additional, van Dyck, Christopher H., additional, Porsteinsson, Anton P., additional, Craft, Suzanne, additional, Levey, Allan, additional, Burke, William J., additional, Mintzer, Jacobo, additional, and Herrmann, Nathan, additional

Published
2023
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38. Correlation between changes in apathy and global cognition in apathetic associated with Alzheimer's disease: analysis of the Apathy Dementia Methylphenidate 2 (ADMET 2) clinical trial

Author

Lanctôt, Krista, primary, Sankhe, Krushnaa, additional, Perin, Jamie, additional, Herrmann, Nathan, additional, Brawman-Mintzer, Olga, additional, Lerner, Alan J., additional, Mintzer, Jacobo, additional, Padala, Prasad R., additional, Rosenberg, Paul B., additional, Shade, David M., additional, van Dyck, Christopher H., additional, and Porsteinsson, Anton P., additional

Published
2023
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39. Additional file 1 of CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer’s disease

Author

Lerner, Alan J., Arnold, Steven E., Maxfield, Erin, Koenig, Aaron, Toth, Maria E., Fortin, Brooke, Mast, Natalia, Trombetta, Bianca A., Denker, John, Pieper, Andrew A., Tatsuoka, Curtis, Raghupathy, Sangeetha, and Pikuleva, Irina A.

Abstract

Additional file 1: Supplemental methods. Supplemental Table 1. Summary of visits and evaluations common for both clinical sites and specific for the MGH site. SC, screening visit; BL, baseline visit; PC, phone call; CV, clinic visit; DC, early discontinuation visit; W, week; *, MGH site only; ** unscheduled visit; 24HC, 24-hydroxycholesterol. Supplemental Fig. 1. A tree showing the screening, enrollment, randomization, and outcome of subjects in the efavirenz clinical trial. UHCMC, Brain Health and Memory Center and the Memory Disorders Clinic in Cleveland, OH; MGH, Alzheimer’s Clinical & Translational Research Unit at Massachusetts General Hospital.

Published
2023
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42. Heterogeneity of response to methylphenidate in apathetic patients in the ADMET 2 Trial

Author

Lanctôt, Krista L., primary, Perin, Jamie, additional, Vieira, Danielle, additional, Rosenberg, Paul B., additional, Herrmann, Nathan, additional, Shade, David, additional, Lerner, Alan J., additional, Padala, Prasad R, additional, Brawman‐Mintzer, Olga, additional, van Dyck, Christopher H, additional, Porsteinsson, Anton P., additional, Craft, Suzanne, additional, Levey, Allan I., additional, and Mintzer, Jacobo E, additional

Published
2022
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43. Association of mitochondrial haplogroups and cognitive impairment in the Amish

Author

Dorfsman, Daniel A., primary, Prough, Michael B., additional, Caywood, Laura J., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Slifer, Susan H., additional, Adams, Larry D., additional, Laux, Renee A., additional, Song, Yeunjoo E., additional, Lynn, Audrey, additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Hochstetler, Sherri D., additional, Miskimen, Kristy L., additional, Main, Leighanne R., additional, Osterman, Michael D., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Haines, Jonathan L., additional, Pericak‐Vance, Margaret A., additional, and Scott, William K., additional

Published
2022
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44. Plasma pTau181 is associated with impaired cognition in the Old Order Amish and adds additional information beyond the known genetic risk factors for AD

Author

Prough, Michael B., primary, Caywood, Laura J., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Slifer, Susan H., additional, Dorfsman, Daniel A., additional, Adams, Larry D., additional, Laux, Renee A., additional, Song, Yeunjoo E., additional, Lynn, Audrey, additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Miller, Sherri D., additional, Miskimen, Kristy L., additional, Main, Leighanne R., additional, Osterman, Michael D., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Haines, Jonathan L., additional, Scott, William K., additional, and Pericak‐Vance, Margaret A., additional

Published
2022
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45. Mosaic Loss of Chromosome Y in Peripheral Blood Cells and Cognitive Status in the Amish

Author

Song, Yeunjoo E., primary, Miskimen, Kristy L., additional, Laux, Renee A., additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Miller, Sherri D., additional, Main, Leighanne R., additional, Osterman, Michael D., additional, Lynn, Audrey, additional, Prough, Michael B., additional, Slifer, Susan H., additional, Adams, Larry D., additional, Caywood, Laura J., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Dorfsman, Daniel A., additional, Vance, Jeffery M., additional, Cuccaro, Michael L., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Scott, William K., additional, Pericak‐Vance, Margaret A., additional, Bush, William S., additional, and Haines, Jonathan L., additional

Published
2022
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46. Detecting genetic loci for preservation of cognition in the Midwestern United States Amish

Author

Main, Leighanne R., primary, Song, Yeunjoo E., additional, Laux, Renee A., additional, Miskimen, Kristy L., additional, Cuccaro, Michael L., additional, Ogrocki, Paula K., additional, Lerner, Alan J., additional, Vance, Jeffery M., additional, Fuzzell, M. Denise, additional, Fuzzell, Sarada L., additional, Hochstetler, Sherri D., additional, Osterman, Michael D., additional, Lynn, Audrey, additional, Dorfsman, Daniel A., additional, Caywood, Laura J., additional, Prough, Michael B., additional, Adams, Larry D., additional, Clouse, Jason E., additional, Herington, Sharlene D., additional, Scott, William K., additional, Pericak‐Vance, Margaret A., additional, and Haines, Jonathan L., additional

Published
2022
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48. Effects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study.

Author

Clark, Emily D., Perin, Jamie, Herrmann, Nathan, Brawman‐Mintzer, Olga, Lanctôt, Krista L., Lerner, Alan J., Mintzer, Jacobo, Padala, Prasad R., Rosenberg, Paul B., Sami, Susie, Shade, David M., van Dyck, Christopher H., and Porsteinsson, Anton P.

Subjects
ALZHEIMER'S disease, METHYLPHENIDATE, ALZHEIMER'S patients, CENTRAL nervous system stimulants
Abstract

INTRODUCTION: Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of methylphenidate on neuropsychiatric symptoms (NPS) of AD, excluding apathy, using data from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) study. METHODS: A secondary analysis was conducted on data from the ADMET 2 study to determine the effect of methylphenidate on Neuropsychiatric Inventory (NPI) scores outside of apathy. Caregiver scores were compared from baseline to month 6 in 199 participants receiving methylphenidate (20 mg/day) or placebo regarding the presence or absence of individual neuropsychiatric symptoms, emergence of new symptoms, and individual domain scores. RESULTS: No clinically meaningful improvement was observed in any NPI domain, excluding apathy, in participants treated with methylphenidate compared to placebo after 6 months. A statistical difference between groups was appreciated in the domains of elation/euphoria (P = 0.044) and appetite/eating disorders (P = 0.014); however, these findings were not considered significant. DISCUSSION: Methylphenidate is a selective agent for symptoms of apathy in patients with AD with no meaningful impact on other NPS. Findings from this secondary analysis are considered exploratory and multiple limitations should be considered when interpreting these results, including small sample size and use of a single questionnaire. HIGHLIGHTS: Methylphenidate was not associated with significant improvement on the Neuropsychiatric Inventory in domains outside of apathy.Methylphenidate did not show a statistically significant emergence of new neuropsychiatric symptoms (NPS) throughout the 6‐month treatment period compared to placebo.Methylphenidate appears to be a highly selective agent for apathy in Alzheimer's disease, potentially supporting catecholaminergic dysfunction as the driving force behind this presentation of symptoms. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Cognition/Psychological Burden and Resilience in Cutaneous T-Cell Lymphoma and Psoriasis Patients: Real-Life Data and Implications for the Treatment

Author

Damiani, Giovanni, primary, Tacastacas, Joselin D., additional, Wuerz, Timothy, additional, Miller, Lindsay, additional, Fastenau, Philip, additional, Bailey, Christopher, additional, Chawa, Mansi Sethi, additional, Argenas, Amanda, additional, Fiore, Marco, additional, Cooper, Kevin D., additional, and Lerner, Alan J., additional

Published
2022
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