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31 Machine Learning Algorithm to Predict Duration to Full Time Care after Alzheimer's Disease Diagnosis
- Jessica H Helphrey, Jayme M Palka, Jake Rossmango, Hudaisa Fatima, Michael Conley, Anthony Longoria, Jennifer Sawyer, Jeffrey Schaffert, Anne Carlew, Munro Cullum, Laura Lacritz, John Hart, Hsueh-Sheng Chiang, Trung Nguyen, Alka Khera, Christian LoBue
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 241
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Objective:
Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.
Participants and Methods:The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged >50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.
Results:The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.
Conclusions:Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.
87 Not Normal but not MCI: Course of Memory over time
- Michael Conley, Jeff Schaffert, Anthony Longoria, Jessica Helphrey, C Munro Cullum, Laura Lacritz
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 389-390
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Objective:
A diagnosis of mild cognitive impairment (MCI) requires memory complaint and objective memory impairment. However, some individuals report subjective memory complaints (SMC) despite having intact memory performance, while others demonstrate subtle impairment on memory testing but have no memory complaints; neither case would meet criteria for MCI. This study aimed to compare memory performances over time in individuals who do not meet traditional MCI criteria to those with normal cognition and those who converted to MCI.
Participants and Methods:Diagnoses for a longitudinal sample from the Texas Alzheimer’s Research and Care Consortium were reviewed by a consensus panel of neuropsychologists and neurologists and reclassified at time of last visit. Diagnostic categories included SMC (i.e., memory complaint but no impairment on testing), objective cognitive impairment but no complaint (Impaired but not MCI), normal control (NC), MCI, and dementia. In this study, 827 participants were divided into 4 groups: 1) NC over 5 visits (n=511, 71% female; 42% Latinx/Hispanic), 2) baseline NC to amnestic MCI (n=62; 63% female; 57% Latinx/Hispanic), 3) SMC at last visit (n=133; 58% female; 70% Latinx/Hispanic), and 4) impaired but not MCI at last visit (n=121; 71% female; 60% Latinx/Hispanic). A memory composite (z-score) was created from the CERAD list-learning task (immediate, delayed, and recognition-discrimination) and Wechsler Memory Scale (Immediate and Delayed Logical Memory and Visual Reproduction) to evaluate memory performance over time. A linear mixed-model adjusting for age, education, sex, ethnicity, and number of APOE e4 alleles evaluated memory performance across 5 visits for the groups. To assess if depression followed a similar course, a linear mixed-model evaluated Geriatric Depression Scale (GDS) scores over time.
Results:At baseline, groups differed by age (F=22.82; p<.001), education (F=8.60; p<.001), MMSE scores (F=9.38; p<.001), GDS-30 scores (F=3.56; p=.015), and memory composites (F=24.29; p<.001). A significant group X time interaction was observed (F=4.83, p<.001). Memory performance improved in both the SMC and the NC groups, remained stable in the impaired but not MCI group, and declined (as expected) in those who converted to amnestic MCI. Depression scores also showed a significant group X time interaction (F=2.43; p=.004), in which the NC to MCI group endorsed slightly more depression symptoms over time, while other groups declined or remained stable.
Conclusions:Memory trajectories in this diverse sample differed across groups. Individuals with SMC but without objective memory impairment and normal controls showed some improvement in memory over time, presumably due to practice effects. Those with subtle memory impairments but no complaint (i.e., did not meet MCI criteria) remained stable and those who converted to amnestic MCI had worse memory across time. The stability of memory performances in the impaired not MCI group suggests these subtle memory inefficiencies may be longstanding or unperceived. However, because our sample achieved retrospective diagnoses of SMC and impaired not MCI, it will be important for future studies to prospectively follow these groups to determine which risk factors may predict progression to MCI and what impact ethnicity may have on these trajectories.
68 Preliminary Evidence of a Therapeutic Effect of Electrical Neuromodulation on Cognitive Deficits in Patients with Mild Cognitive Impairment
- Christian LoBue, Didehbani Nyaz, Hsueh-Sheng Chiang, John Hart, Jessica Helphrey, Michael Conley, Eric Smernoff, Laura Lacritz, Caitlin Reese, C M Cullum, Cindy Marshall, Trung Nguyen, Brendan J Kelley, Alka Khera, Alex Frolov, Natalie Martinez, Rebecca Logan
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 475
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Objective:
Episodic memory functioning is distributed across two brain circuits, one of which courses through the dorsal anterior cingulate cortex (dACC). Thus, delivering non-invasive neuromodulation technology to the dACC may improve episodic memory functioning in patients with memory problems such as in amnestic mild cognitive impairment (aMCI). This preliminary study is a randomized, double-blinded, sham-controlled clinical trial to examine if high definition transcranial direct current stimulation (HD-tDCS) can be a viable treatment in aMCI.
Participants and Methods:Eleven aMCI participants, of whom 9 had multidomain deficits, were randomized to receive 1 mA HD-tDCS (N=7) or sham (N=4) stimulation. HD-tDCS was applied over ten 20-minute sessions targeting the dACC. Neuropsychological measures of episodic memory, verbal fluency, and executive function were completed at baseline and after the last HD-tDCS session. Changes in composite scores for memory and language/executive function tests were compared between groups (one-tailed t-tests with a = 0.10 for significance). Clinically significant change, defined as > 1 SD improvement on at least one test in the memory and non-memory domains, was compared between active and sham stimulation based on the frequency of participants in each.
Results:No statistical or clinically significant change (N-1 X2; p = 0.62) was seen in episodic memory for the active HD-tDCS (MDiff = 4.4; SD = 17.1) or sham groups (MDiff = -0.5; SD = 9.7). However, the language and executive function composite showed statistically significant improvement (p = 0.04; MDiff = -15.3; SD = 18.4) for the active HD-tDCS group only (Sham MDiff = -5.8; SD = 10.7). Multiple participants (N=4) in the active group had clinically significant enhancement in language and executive functioning tests, while nobody in the sham group did (p = 0.04).
Conclusions:HD-tDCS targeting the dACC had no direct benefit for episodic memory deficits in aMCI based on preliminary findings for this ongoing clinical trial. However, significant improvement in language and executive function skills occurred in response to HD-tDCS, suggesting HD-tDCS in this configuration has promising potential as an intervention for language and executive function deficits in MCI.
Mars: new insights and unresolved questions – Corrigendum
- Hitesh G. Changela, Elias Chatzitheodoridis, Andre Antunes, David Beaty, Kristian Bouw, John C. Bridges, Klara Anna Capova, Charles S. Cockell, Catharine A. Conley, Ekaterina Dadachova, Tiffany D. Dallas, Stefaan de Mey, Chuanfei Dong, Alex Ellery, Martin Ferus, Bernard Foing, Xiaohui Fu, Kazuhisa Fujita, Yangting Lin, Sohan Jheeta, Leon J. Hicks, Sen Hu, Akos Kereszturi, Alexandros Krassakis, Yang Liu, Juergen Oberst, Joe Michalski, P. M. Ranjith, Teresa Rinaldi, David Rothery, Hector A. Stavrakakis, Laura Selbmann, Rishitosh K. Sinha, Alian Wang, Ken Williford, Zoltan Vaci, Jorge L. Vago, Michael Waltemathe, John E. Hallsworth
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- Journal:
- International Journal of Astrobiology / Volume 21 / Issue 1 / February 2022
- Published online by Cambridge University Press:
- 10 January 2022, p. 46
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Mars: new insights and unresolved questions
- Hitesh G. Changela, Elias Chatzitheodoridis, Andre Antunes, David Beaty, Kristian Bouw, John C. Bridges, Klara Anna Capova, Charles S. Cockell, Catharine A. Conley, Ekaterina Dadachova, Tiffany D. Dallas, Stefaan de Mey, Chuanfei Dong, Alex Ellery, Martin Ferus, Bernard Foing, Xiaohui Fu, Kazuhisa Fujita, Yangting Lin, Sohan Jheeta, Leon J. Hicks, Sen Hu, Akos Kereszturi, Alexandros Krassakis, Yang Liu, Juergen Oberst, Joe Michalski, P. M. Ranjith, Teresa Rinaldi, David Rothery, Hector A. Stavrakakis, Laura Selbmann, Rishitosh K. Sinha, Alian Wang, Ken Williford, Zoltan Vaci, Jorge L. Vago, Michael Waltemathe, John E. Hallsworth
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- Journal:
- International Journal of Astrobiology / Volume 20 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 01 December 2021, pp. 394-426
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Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018)
- Max Lam, Joey W. Trampush, Jin Yu, Emma Knowles, Srdjan Djurovic, Ingrid Melle, Kjetil Sundet, Andrea Christoforou, Ivar Reinvang, Pamela DeRosse, Astri J. Lundervold, Vidar M. Steen, Thomas Espeseth, Katri Räikkönen, Elisabeth Widen, Aarno Palotie, Johan G. Eriksson, Ina Giegling, Bettina Konte, Panos Roussos, Stella Giakoumaki, Katherine E. Burdick, Antony Payton, William Ollier, Ornit Chiba-Falek, Deborah K. Attix, Anna C. Need, Elizabeth T. Cirulli, Aristotle N. Voineskos, Nikos C. Stefanis, Dimitrios Avramopoulos, Alex Hatzimanolis, Dan E. Arking, Nikolaos Smyrnis, Robert M. Bilder, Nelson A. Freimer, Tyrone D. Cannon, Edythe London, Russell A. Poldrack, Fred W. Sabb, Eliza Congdon, Emily Drabant Conley, Matthew A. Scult, Dwight Dickinson, Richard E. Straub, Gary Donohoe, Derek Morris, Aiden Corvin, Michael Gill, Ahmad R. Hariri, Daniel R. Weinberger, Neil Pendleton, Panos Bitsios, Dan Rujescu, Jari Lahti, Stephanie Le Hellard, Matthew C. Keller, Ole A. Andreassen, David C. Glahn, Anil K. Malhotra, Todd Lencz
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- Journal:
- Twin Research and Human Genetics / Volume 21 / Issue 5 / October 2018
- Published online by Cambridge University Press:
- 13 July 2018, pp. 394-397
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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Morphology of retinogeniculate axons in the macaque
- Michael Conley, David Fitzpatrick
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- Visual Neuroscience / Volume 2 / Issue 3 / March 1989
- Published online by Cambridge University Press:
- 02 June 2009, pp. 287-296
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The size, pattern of terminal arborizations, and laminar specificity of individual retinogeniculate axons were studied in the macaque following injections of HRP into the optic tract. Axons that terminated in the magnocellular layers had significantly larger fiber diameters and wider terminal fields than those that terminated in the parvocellular layers. Terminal fields of magnocellular fibers spanned most of the width of their target layer, whereas those of parvocellular fibers were restricted to approximately one-half the width of their target layers; almost all terminal fields were oriented along lines of projection. All of the optic tract fibers that we examined terminated in only one layer of the lateral geniculate nucleus (GL), including a population of fine caliber fibers that project to the intercalated layers, and none had collateral projections outside the GL. The results suggest that each layer – magnocellular, parvocellular, and intercalated – receives projections from a morphologically distinct population of optic tract fibers.