41 results on '"Stern, Robert"'
Search Results
2. Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
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Alosco, Michael L, Su, Yi, Stein, Thor D, Protas, Hillary, Cherry, Jonathan D, Adler, Charles H, Balcer, Laura J, Bernick, Charles, Pulukuri, Surya Vamsi, Abdolmohammadi, Bobak, Coleman, Michael J, Palmisano, Joseph N, Tripodis, Yorghos, Mez, Jesse, Rabinovici, Gil D, Marek, Kenneth L, Beach, Thomas G, Johnson, Keith A, Huber, Bertrand Russell, Koerte, Inga, Lin, Alexander P, Bouix, Sylvain, Cummings, Jeffrey L, Shenton, Martha E, Reiman, Eric M, McKee, Ann C, and Stern, Robert A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Aging ,Physical Injury - Accidents and Adverse Effects ,Acquired Cognitive Impairment ,Brain Disorders ,Alzheimer's Disease ,Dementia ,Neurosciences ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurological ,Humans ,Alzheimer Disease ,Autopsy ,Brain ,Brain Injuries ,Traumatic ,Chronic Traumatic Encephalopathy ,Death ,Football ,Positron-Emission Tomography ,tau Proteins ,Biomarkers ,Chronic traumatic encephalopathy ,Neurodegenerative disease ,Positron emission tomography imaging ,Repetitive head impacts ,Tau ,Flortaucipir ,DIAGNOSE C. T. E. Research Project ,Other Physical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeFlourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.MethodsThree former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).ResultsFour brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.ConclusionsFlortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
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- 2023
3. Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project
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Stern, Robert A., Trujillo-Rodriguez, Diana, Tripodis, Yorghos, Pulukuri, Surya V., Alosco, Michael L., Adler, Charles H., Balcer, Laura J., Bernick, Charles, Baucom, Zachary, Marek, Kenneth L., McClean, Michael D., Johnson, Keith A., McKee, Ann C., Stein, Thor D., Mez, Jesse, Palmisano, Joseph N., Cummings, Jeffrey L., Shenton, Martha E., and Reiman, Eric M.
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- 2023
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4. Neuropsychological test performance of former American football players
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Alosco, Michael L., Barr, William B., Banks, Sarah J., Wethe, Jennifer V., Miller, Justin B., Pulukuri, Surya Vamsi, Culhane, Julia, Tripodis, Yorghos, Adler, Charles H., Balcer, Laura J., Bernick, Charles, Mariani, Megan L., Cantu, Robert C., Dodick, David W., McClean, Michael D., Au, Rhoda, Mez, Jesse, Turner, II, Robert W., Palmisano, Joseph N., Martin, Brett, Hartlage, Kaitlin, Cummings, Jeffrey L., Reiman, Eric M., Shenton, Martha E., and Stern, Robert A.
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- 2023
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5. Failure to detect an association between self‐reported traumatic brain injury and Alzheimer's disease neuropathology and dementia
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Sugarman, Michael A, McKee, Ann C, Stein, Thor D, Tripodis, Yorghos, Besser, Lilah M, Martin, Brett, Palmisano, Joseph N, Steinberg, Eric G, O'Connor, Maureen K, Au, Rhoda, McClean, Michael, Killiany, Ronald, Mez, Jesse, Weiner, Michael W, Kowall, Neil W, Stern, Robert A, and Alosco, Michael L
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Biological Psychology ,Psychology ,Physical Injury - Accidents and Adverse Effects ,Prevention ,Traumatic Brain Injury (TBI) ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Dementia ,Traumatic Head and Spine Injury ,Alzheimer's Disease ,Neurosciences ,Acquired Cognitive Impairment ,Aging ,Neurodegenerative ,Neurological ,Injuries and accidents ,Aged ,Alzheimer Disease ,Autopsy ,Brain Injuries ,Traumatic ,Cognition ,Databases ,Factual ,Female ,Humans ,Interviews as Topic ,Male ,Neuropathology ,Risk Factors ,Self Report ,Alzheimer's disease ,Traumatic brain injury ,Cognitive decline ,Neurodegenerative disease ,NACC ,Concussion ,Clinical Sciences ,Geriatrics ,Clinical sciences ,Biological psychology - Abstract
IntroductionRecent research with neuropathologic or biomarker evidence of Alzheimer's disease (AD) casts doubt on traumatic brain injury (TBI) as a risk factor for AD. We leveraged the National Alzheimer's Coordinating Center to examine the association between self-reported TBI with loss of consciousness and AD neuropathologic changes, and with baseline and longitudinal clinical status.MethodsThe sample included 4761 autopsy participants (453 with remote TBI with loss of consciousness; 2822 with AD neuropathologic changes) from National Alzheimer's Coordinating Center.ResultsSelf-reported TBI did not predict AD neuropathologic changes (P > .10). Reported TBI was not associated with baseline or change in dementia severity or cognitive function in participants with or without autopsy-confirmed AD.DiscussionSelf-reported TBI with loss of consciousness may not be an independent risk factor for clinical or pathological AD. Research that evaluates number and severity of TBIs is needed to clarify the neuropathological links between TBI and dementia documented in other large clinical databases.
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- 2019
6. A comparison between tau and amyloid-β cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease
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Turk, Katherine W., Geada, Alexandra, Alvarez, Victor E., Xia, Weiming, Cherry, Jonathan D., Nicks, Raymond, Meng, Gaoyuan, Daley, Sarah, Tripodis, Yorghos, Huber, Bertrand R., Budson, Andrew E., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., Alosco, Michael L., Mez, Jesse, McKee, Ann C., and Stein, Thor D.
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- 2022
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7. Clinical and Neuropathological Correlates of Substance Use in American Football Players.
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Walsh, Michael, Uretsky, Madeline, Tripodis, Yorghos, Nowinski, Christopher J., Rasch, Abigail, Bruce, Hannah, Ryder, Megan, Martin, Brett M., Palmisano, Joseph N., Katz, Douglas I., Dwyer, Brigid, Daneshvar, Daniel H., Walley, Alexander Y., Kim, Theresa W., Goldstein, Lee E., Stern, Robert A., Alvarez, Victor E., Huber, Bertrand Russell, McKee, Ann C., and Stein, Thor D.
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CHRONIC traumatic encephalopathy ,ALZHEIMER'S disease ,SUBSTANCE abuse ,BRAIN injuries ,HEAD injuries - Abstract
Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR
2 = 0.04–0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02–0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms. [ABSTRACT FROM AUTHOR]- Published
- 2024
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8. Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms.
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Frank, Brandon, Walsh, Michael, Hurley, Landon, Groh, Jenna, Blennow, Kaj, Zetterberg, Henrik, Tripodis, Yorghos, Budson, Andrew E., O'Connor, Maureen K., Martin, Brett, Weller, Jason, McKee, Ann, Qiu, Wendy, Stein, Thor D., Stern, Robert A., Mez, Jesse, Henson, Rachel, Long, Justin, Aschenbrenner, Andrew J., and Babulal, Ganesh M.
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ALZHEIMER'S disease ,STRUCTURAL equation modeling ,CEREBROSPINAL fluid ,NEUROPSYCHOLOGICAL tests ,OLDER people - Abstract
Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear. Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ
1-42 , p-tau181 ), cognitive function, and NPS. Methods: Primary models included 781 participants from the National Alzheimer's Coordinating Center (NACC) data set who had CSF analyzed for AD biomarkers using Lumipulse. NPS were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). We assessed cognition with the harmonized MMSE/MoCA, as well as neuropsychological tests sensitive to AD pathology: story recall, naming, animal fluency, and Trails B. The Clinical Dementia Rating (CDR® ) scale assessed dementia severity. Mediation models were estimated with Kemeny metric covariance in a structural equation model framework, controlling for age, education, sex, and APOEɛ4. Results: The sample was older adults (M = 73.85, SD = 6.68; 49.9% male, 390; 27.9% dementia, 218) who were predominantly white (n = 688, 88.1%). Higher p-tau181 /Aβ1-42 ratio predicted higher NPI-Q, which was partially mediated by the MMSE/MoCA and, in a second model, story recall. No other pathway was statistically significant. Both the MMSE/MoCA and NPI-Q independently mediated the association between p-tau181 /Aβ1-42 ratio and CDR global impairment. With dementia excluded, p-tau181 /Aβ1-42 ratio was no longer associated with the NPI-Q. Conclusions: NPS may be secondary to cognitive impairment and AD pathology through direct and indirect pathways. NPS independently predict dementia severity in AD. However, AD pathology likely plays less of a role in NPS in samples without dementia. [ABSTRACT FROM AUTHOR]- Published
- 2024
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9. A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer’s Disease Neuropathology
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Alosco, Michael L, Sugarman, Michael A, Besser, Lilah M, Tripodis, Yorghos, Martin, Brett, Palmisano, Joseph N, Kowall, Neil W, Au, Rhoda, Mez, Jesse, DeCarli, Charles, Stein, Thor D, McKee, Ann C, Killiany, Ronald J, and Stern, Robert A
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Biomedical and Clinical Sciences ,Biological Psychology ,Clinical Sciences ,Neurosciences ,Psychology ,Dementia ,Alzheimer's Disease ,Brain Disorders ,Neurodegenerative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Clinical Research ,Aging ,Vascular Cognitive Impairment/Dementia ,Acquired Cognitive Impairment ,Neurological ,Aged ,Aged ,80 and over ,Alzheimer Disease ,Apolipoproteins E ,Brain ,Female ,Humans ,Leukoencephalopathies ,Logistic Models ,Magnetic Resonance Imaging ,Male ,Neuropathology ,Psychiatric Status Rating Scales ,Alzheimer's disease ,Alzheimer's disease neuropathology ,cerebrovascular disease ,dementia ,magnetic resonance imaging ,white matter hyperintensities ,Alzheimer’s disease ,Alzheimer’s disease neuropathology ,cerebrovascular disease ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
BackgroundWhite matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility.ObjectiveThis study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP.MethodsThe sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy.Results60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps
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- 2018
10. The Effect of Traumatic Brain Injury History with Loss of Consciousness on Rate of Cognitive Decline Among Older Adults with Normal Cognition and Alzheimer’s Disease Dementia
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Tripodis, Yorghos, Alosco, Michael L, Zirogiannis, Nikolaos, Gavett, Brandon E, Chaisson, Christine, Martin, Brett, McClean, Michael D, Mez, Jesse, Kowall, Neil, and Stern, Robert A
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Biological Psychology ,Clinical and Health Psychology ,Psychology ,Aging ,Neurodegenerative ,Brain Disorders ,Traumatic Head and Spine Injury ,Acquired Cognitive Impairment ,Traumatic Brain Injury (TBI) ,Neurosciences ,Clinical Research ,Behavioral and Social Science ,Dementia ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Physical Injury - Accidents and Adverse Effects ,Alzheimer's Disease ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Injuries and accidents ,Neurological ,Aged ,Aged ,80 and over ,Alzheimer Disease ,Apolipoprotein E4 ,Attention ,Brain Injuries ,Case-Control Studies ,Cognition Disorders ,Cohort Studies ,Executive Function ,Female ,Humans ,Male ,Middle Aged ,Models ,Statistical ,Neuropsychological Tests ,Psychiatric Status Rating Scales ,Unconsciousness ,Alzheimer's disease ,APOE ,cognitive decline ,dementia ,loss of consciousness ,normal cognition ,risk factor ,traumatic brain injury ,Alzheimer’s disease ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
Traumatic brain injury (TBI) is thought to be a risk factor for dementia, including dementia due to Alzheimer's disease (AD). However, the influence of TBI history on the neuropsychological course of AD is unknown and, more broadly, the effect of TBI history on age-related cognitive change is poorly understood. We examined the relationship between history of TBI with loss of consciousness (LOC) history and cognitive change in participants with normal cognition and probable AD, stratified by APOEɛ4 allele status. The sample included 706 participants (432 with normal cognition; 274 probable AD) from the National Alzheimer's Coordinating Center (NACC) dataset that completed the Uniform Data Set evaluation between 2005 and 2014. Normal and probable AD participants with a history of TBI were matched to an equal number of demographically and clinically similar participants without a TBI history. In this dataset, TBI with LOC was defined as brain trauma with brief or extended unconsciousness. For the normal and probable AD cohorts, there was an average of 3.2±1.9 and 1.8±1.1 years of follow-up, respectively. 30.8% of the normal cohort were APOEɛ4 carriers, whereas 70.8% of probable AD participants were carriers. Mixed effects regressions showed TBI with LOC history did not affect rates of cognitive change in APOEɛ4 carriers and non-carriers. Findings from this study suggest that TBI with LOC may not alter the course of cognitive function in older adults with and without probable AD. Future studies that better characterize TBI (e.g., severity, number of TBIs, history of subconconcussive exposure) are needed to clarify the association between TBI and long-term neurocognitive outcomes.
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- 2017
11. Practice Effects on Story Memory and List Learning Tests in the Neuropsychological Assessment of Older Adults.
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Gavett, Brandon E, Gurnani, Ashita S, Saurman, Jessica L, Chapman, Kimberly R, Steinberg, Eric G, Martin, Brett, Chaisson, Christine E, Mez, Jesse, Tripodis, Yorghos, and Stern, Robert A
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Humans ,Alzheimer Disease ,Disease Progression ,Memory ,Short-Term ,Mental Recall ,Neuropsychological Tests ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Cognitive Dysfunction ,Dementia ,Clinical Research ,Neurosciences ,Brain Disorders ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Acquired Cognitive Impairment ,Basic Behavioral and Social Science ,Alzheimer's Disease ,Aging ,Neurodegenerative ,Behavioral and Social Science ,Mental health ,Neurological ,General Science & Technology - Abstract
Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed-but not the immediate-recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants-but not participants with AD-improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects-especially on the delayed recall condition-suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis.
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- 2016
12. Relative Contributions of Mixed Pathologies to Cognitive and Functional Symptoms in Brain Donors Exposed to Repetitive Head Impacts.
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Saltiel, Nicole, Tripodis, Yorghos, Menzin, Talia, Olaniyan, Aliyah, Baucom, Zach, Yhang, Eukyung, Palmisano, Joseph N., Martin, Brett, Uretsky, Madeline, Nair, Evan, Abdolmohammadi, Bobak, Shah, Arsal, Nicks, Raymond, Nowinski, Christopher, Cantu, Robert C., Daneshvar, Daniel H., Dwyer, Brigid, Katz, Douglas I., Stern, Robert A., and Alvarez, Victor E.
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HEAD injuries ,CHRONIC traumatic encephalopathy ,CEREBRAL amyloid angiopathy ,HIPPOCAMPAL sclerosis ,SYMPTOMS ,ALZHEIMER'S disease - Abstract
Objective: Exposure to repetitive head impacts (RHI) is associated with later‐life cognitive symptoms and neuropathologies, including chronic traumatic encephalopathy (CTE). Cognitive decline in community cohorts is often due to multiple pathologies; however, the frequency and contributions of these pathologies to cognitive impairment in people exposed to RHI are unknown. Here, we examined the relative contributions of 13 neuropathologies to cognitive symptoms and dementia in RHI‐exposed brain donors. Methods: Neuropathologists examined brain tissue from 571 RHI‐exposed donors and assessed for the presence of 13 neuropathologies, including CTE, Alzheimer disease (AD), Lewy body disease (LBD), and transactive response DNA‐binding protein 43 (TDP‐43) inclusions. Cognitive status was assessed by presence of dementia, Functional Activities Questionnaire, and Cognitive Difficulties Scale. Spearman rho was calculated to assess intercorrelation of pathologies. Additionally, frequencies of pathological co‐occurrence were compared to a simulated distribution assuming no intercorrelation. Logistic and linear regressions tested associations between neuropathologies and dementia status and cognitive scale scores. Results: The sample age range was 18–97 years (median = 65.0, interquartile range = 46.0–76.0). Of the donors, 77.2% had at least one moderate–severe neurodegenerative or cerebrovascular pathology. Stage III–IV CTE was the most common neurodegenerative disease (43.1%), followed by TDP‐43 pathology, AD, and hippocampal sclerosis. Neuropathologies were intercorrelated, and there were fewer unique combinations than expected if pathologies were independent (p < 0.001). The greatest contributors to dementia were AD, neocortical LBD, hippocampal sclerosis, cerebral amyloid angiopathy, and CTE. Interpretation: In this sample of RHI‐exposed brain donors with wide‐ranging ages, multiple neuropathologies were common and correlated. Mixed neuropathologies, including CTE, underlie cognitive impairment in contact sport athletes. ANN NEUROL 2024;95:314–324 [ABSTRACT FROM AUTHOR]
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- 2024
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13. Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy
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Standring, Oliver J., Friedberg, Jacob, Tripodis, Yorghos, Chua, Alicia S., Cherry, Jonathan D., Alvarez, Victor E., Huber, Bertrand R., Xia, Weiming, Mez, Jesse, Alosco, Michael L., Nicks, Raymond, Mahar, Ian, Pothast, Morgan J., Gardner, Hannah M., Meng, Gaoyuan, Palmisano, Joseph N., Martin, Brett M., Dwyer, Brigid, Kowall, Neil W., Cantu, Robert C., Goldstein, Lee E., Katz, Douglas I., Stern, Robert A., McKee, Ann C., and Stein, Thor D.
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- 2019
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14. Overview of the Oxford Handbook of Adult Cognitive Disorders
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Alosco, Michael L., Stern, Robert A., Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
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15. Severe CTE and TDP-43 pathology in a former professional soccer player with dementia: a clinicopathological case report and review of the literature.
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van Amerongen, Suzan, Kamps, Suzie, Kaijser, Kyra K. M., Pijnenburg, Yolande A. L., Scheltens, Philip, Teunissen, Charlotte E., Barkhof, Frederik, Ossenkoppele, Rik, Rozemuller, Annemieke J. M., Stern, Robert A., Hoozemans, Jeroen J. M., and Vijverberg, Everard G. B.
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SOCCER players ,CHRONIC traumatic encephalopathy ,ALZHEIMER'S disease ,CLINICAL pathology ,AUTOPSY ,FEEDING tubes - Abstract
In the last decades, numerous post-mortem case series have documented chronic traumatic encephalopathy (CTE) in former contact-sport athletes, though reports of CTE pathology in former soccer players are scarce. This study presents a clinicopathological case of a former professional soccer player with young-onset dementia. The patient experienced early onset progressive cognitive decline and developed dementia in his mid-50 s, after playing soccer for 12 years at a professional level. While the clinical picture mimicked Alzheimer's disease, amyloid PET imaging did not provide evidence of elevated beta-amyloid plaque density. After he died in his mid-60 s, brain autopsy showed severe phosphorylated tau (p-tau) abnormalities fulfilling the neuropathological criteria for high-stage CTE, as well as astrocytic and oligodendroglial tau pathology in terms of tufted astrocytes, thorn-shaped astrocytes, and coiled bodies. Additionally, there were TAR DNA-binding protein 43 (TDP-43) positive cytoplasmic inclusions in the frontal lobe and hippocampus, and Amyloid Precursor Protein (APP) positivity in the axons of the white matter. A systematic review of the literature revealed only 13 other soccer players with postmortem diagnosis of CTE. Our report illustrates the complex clinicopathological correlation of CTE and the need for disease-specific biomarkers. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Associations between near end-of-life flortaucipir PET and postmortem CTE-related tau neuropathology in six former American football players
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Alosco, Michael L, Su, Yi, Stein, Thor D, Protas, Hillary, Cherry, Jonathan D, Adler, Charles H, Balcer, Laura J, Bernick, Charles, Pulukuri, Surya Vamsi, Abdolmohammadi, Bobak, Coleman, Michael J, Palmisano, Joseph N, Tripodis, Yorghos, Mez, Jesse, Rabinovici, Gil D, Marek, Kenneth L, Beach, Thomas G, Johnson, Keith A, Huber, Bertrand Russell, Koerte, Inga, Lin, Alexander P, Bouix, Sylvain, Cummings, Jeffrey L, Shenton, Martha E, Reiman, Eric M, McKee, Ann C, Stern, Robert A, and DIAGNOSE C. T. E. Research Project
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Traumatic ,Aging ,Physical Injury - Accidents and Adverse Effects ,DIAGNOSE C. T. E. Research Project ,Clinical Sciences ,Football ,tau Proteins ,Neurodegenerative ,Neurodegenerative disease ,Alzheimer's Disease ,Chronic Traumatic Encephalopathy ,Alzheimer Disease ,Acquired Cognitive Impairment ,Humans ,Positron emission tomography imaging ,Flortaucipir ,Neurosciences ,Brain ,Repetitive head impacts ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Brain Disorders ,Death ,Other Physical Sciences ,Nuclear Medicine & Medical Imaging ,Positron-Emission Tomography ,Brain Injuries ,Neurological ,Dementia ,Autopsy ,Tau ,Biomarkers - Abstract
PurposeFlourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players.MethodsThree former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs).ResultsFour brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions.ConclusionsFlortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
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- 2022
17. Beta-amyloid deposition in chronic traumatic encephalopathy
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Stein, Thor D., Montenigro, Philip H., Alvarez, Victor E., Xia, Weiming, Crary, John F., Tripodis, Yorghos, Daneshvar, Daniel H., Mez, Jesse, Solomon, Todd, Meng, Gaoyuan, Kubilus, Caroline A., Cormier, Kerry A., Meng, Steven, Babcock, Katharine, Kiernan, Patrick, Murphy, Lauren, Nowinski, Christopher J., Martin, Brett, Dixon, Diane, Stern, Robert A., Cantu, Robert C., Kowall, Neil W., and McKee, Ann C.
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- 2015
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18. Early Stages of Alzheimer's Disease: Evolving the Care Team for Optimal Patient Management.
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Galvin, James E., Aisen, Paul, Langbaum, Jessica B., Rodriguez, Eric, Sabbagh, Marwan, Stefanacci, Richard, Stern, Robert A., Vassey, Elizabeth A., de Wilde, Arno, West, Neva, and Rubino, Ivana
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ALZHEIMER'S disease ,HEALTH care teams ,PATIENTS' families ,NEURODEGENERATION - Abstract
Alzheimer's disease (AD) is a progressive, neurodegenerative disease that creates complex challenges and a significant burden for patients and caregivers. Although underlying pathological changes due to AD may be detected in research studies decades prior to symptom onset, many patients in the early stages of AD remain undiagnosed in clinical practice. Increasing evidence points to the importance of an early and accurate AD diagnosis to optimize outcomes for patients and their families, yet many barriers remain along the diagnostic journey. Through a series of international working group meetings, a diverse group of experts contributed their perspectives to create a blueprint for a patient-centered diagnostic journey for individuals in the early stages of AD and an evolving, transdisciplinary care team. Here, we discuss key learnings, implications, and recommendations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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19. Revised Framingham Stroke Risk Profile: Association with Cognitive Status and MRI-Derived Volumetric Measures.
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Pelcher, Isabelle, Puzo, Christian, Tripodis, Yorghos, Aparicio, Hugo J., Steinberg, Eric G., Phelps, Alyssa, Martin, Brett, Palmisano, Joseph N., Vassey, Elizabeth, Lindbergh, Cutter, McKee, Ann C., Stein, Thor D., Killiany, Ronald J., Au, Rhoda, Kowall, Neil W., Stern, Robert A., Mez, Jesse, and Alosco, Michael L.
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COGNITIVE aging ,TRAIL Making Test ,WHITE matter (Nerve tissue) ,STROKE ,LANGUAGE ability testing ,BLOOD pressure ,BRAIN ,ANTIHYPERTENSIVE agents ,RESEARCH ,HIPPOCAMPUS (Brain) ,ANTHROPOMETRY ,AGE distribution ,RESEARCH methodology ,COGNITION ,CARDIOVASCULAR diseases ,DIABETES ,MAGNETIC resonance imaging ,ATRIAL fibrillation ,MEDICAL cooperation ,EVALUATION research ,NEUROPSYCHOLOGICAL tests ,SEX distribution ,COMPARATIVE studies ,RESEARCH funding ,SMOKING - Abstract
Background: The Framingham Stroke Risk Profile (FSRP) was created in 1991 to estimate 10-year risk of stroke. It was revised in 2017 (rFSRP) to reflect the modern data on vascular risk factors and stroke risk.Objective: This study examined the association between the rFSRP and cognitive and brain aging outcomes among participants from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS).Methods: Cross-sectional rFSRP was computed at baseline for 19,309 participants (mean age = 72.84, SD = 8.48) from the NACC-UDS [9,697 (50.2%) normal cognition, 4,705 (24.4%) MCI, 4,907 (25.4%) dementia]. Multivariable linear, logistic, or ordinal regressions examined the association between the rFSRP and diagnostic status, neuropsychological test performance, CDR® Sum of Boxes, as well as total brain volume (TBV), hippocampal volume (HCV), and log-transformed white matter hyperintensities (WMH) for an MRI subset (n = 1,196). Models controlled for age, sex, education, racial identity, APOEɛ4 status, and estimated intracranial volume for MRI models.Results: The mean rFSRP probability was 10.42% (min = 0.50%, max = 95.71%). Higher rFSRP scores corresponded to greater CDR Sum of Boxes (β= 0.02, p = 0.028) and worse performance on: Trail Making Test A (β= 0.05, p < 0.001) and B (β= 0.057, p < 0.001), and Digit Symbol (β= -0.058, p < 0.001). Higher rFSRP scores were associated with increased odds for a greater volume of log-transformed WMH (OR = 1.02 per quartile, p = 0.015). No associations were observed for diagnosis, episodic memory or language test scores, HCV, or TBV.Conclusion: These results support the rFSRP as a useful metric to facilitate clinical research on the associations between cerebrovascular disease and cognitive and brain aging. [ABSTRACT FROM AUTHOR]- Published
- 2020
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20. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease.
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Wessels, Alette M., Lines, Christopher, Stern, Robert A., Kost, James, Voss, Tiffini, Mozley, Lyn Harper, Furtek, Christine, Mukai, Yuki, Aisen, Paul S., Cummings, Jeffrey L., Tariot, Pierre N., Vellas, Bruno, Dupre, Nicole, Randolph, Christopher, Michelson, David, Andersen, Scott W., Shering, Craig, Sims, John R., and Egan, Michael F.
- Abstract
Introduction: The APECS and AMARANTH trials showed that beta‐secretase (BACE) inhibitors verubecestat and lanabecestat failed to slow cognitive and functional decline in individuals with prodromal or early Alzheimer's disease. Here, the performance on secondary and exploratory cognitive measures in both studies is reported. Methods: APECS (verubecestat) and AMARANTH (lanabecestat) were randomized, double‐blind, placebo‐controlled, parallel‐group, 104‐week clinical trials conducted by different sponsors. Measures included the 3‐Domain Composite Cognition Score (CCS‐3D), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Letter/Category Fluency, and Digit Symbol Coding. Results: Verubecestat showed worsening on the CCS‐3D Total Score, Episodic Memory, and Attention/Processing Speed domains. Lanabecestat showed worsening on the RBANS Total Score, Immediate Memory, and Visuospatial/Constructional Indexes. Both BACE inhibitors showed worsening on Digit Symbol Coding and improvements on Letter/Category Fluency. Discussion: In both studies, many measures showed treatment‐associated cognitive worsening, whereas verbal fluency tasks showed improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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21. Differentiating Between Healthy Control Participants and Those with Mild Cognitive Impairment Using Volumetric MRI Data.
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DeVivo, Renée, Zajac, Lauren, Mian, Asim, Cervantes-Arslanian, Anna, Steinberg, Eric, Alosco, Michael L., Mez, Jesse, Stern, Robert, and Killany, Ronald
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MILD cognitive impairment ,ENTORHINAL cortex ,TEMPORAL lobe ,ALZHEIMER'S disease ,MAGNETIC resonance imaging - Abstract
Objective: To determine whether volumetric measures of the hippocampus, entorhinal cortex, and other cortical measures can differentiate between cognitively normal individuals and subjects with mild cognitive impairment (MCI). Method: Magnetic resonance imaging (MRI) data from 46 cognitively normal subjects and 50 subjects with MCI as part of the Boston University Alzheimer's Disease Center research registry and the Alzheimer's Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical, subcortical, and hippocampal subfield volumes were generated from each subject's MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to identify subjects as control or MCI. Results: A model containing regions of interest (superior temporal cortex, caudal anterior cingulate, pars opercularis, subiculum, precentral cortex, caudal middle frontal cortex, rostral middle frontal cortex, pars orbitalis, middle temporal cortex, insula, banks of the superior temporal sulcus, parasubiculum, paracentral lobule) fit the data best (R
2 =.7310, whole model test chi-square = 97.16, p <.0001). Conclusions: MRI data correctly classified most subjects using measures of selected medial temporal lobe structures in combination with those from other cortical areas, yielding an overall classification accuracy of 93.75%. These findings support the notion that, while volumes of medial temporal lobe regions differ between cognitively normal and MCI subjects, differences that can be used to distinguish between these two populations are present elsewhere in the brain. [ABSTRACT FROM AUTHOR]- Published
- 2019
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22. Nailfold Capillary Morphology in Alzheimer's Disease Dementia.
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Steinberg, Eric G., Chapman, Kimberly R., Bing-Canar, Hanaan, Cousins, Clara C., Alosco, Michael L., Stern, Robert A., Chua, Alicia, Tripodis, Yorghos, Pasquale, Louis R., Cousins, Henry C., and Knepper, Paul A.
- Subjects
CEREBROVASCULAR disease risk factors ,CAPILLAROSCOPY ,BIOLOGICAL tags ,ALZHEIMER'S disease ,DEMENTIA ,FINGERNAILS ,CAPILLARIES ,COGNITION disorders ,NEUROPSYCHOLOGICAL tests ,NAILS (Anatomy) ,VIDEO recording ,RETROSPECTIVE studies - Abstract
Background: Cerebrovascular disease (CVD) is highly comorbid with Alzheimer's disease (AD), yet its role is not entirely understood. Nailfold video capillaroscopy (NVC) is a noninvasive method of live imaging the capillaries near the fingernail's cuticle and may help to describe further vascular contributions to AD.Objective: To examine finger nailfold capillary morphology using NVC in subjects with AD dementia, mild cognitive impairment (MCI), and normal cognition (NC).Methods: We evaluated nailfold capillary hemorrhages, avascular zones ≥100 microns, and degree of tortuosity in 28 NC, 15 MCI, and 18 AD dementia subjects using NVC. Tortuosity was measured with a semi-quantitative rating scale. To assess the relation between nailfold capillary morphological features and diagnostic grouping, univariate and multivariable logistic regression models were fit to the data.Results: 56% of subjects with AD dementia compared to 14% with NC and 13% with MCI displayed moderate to severe tortuosity. Greater severity of tortuosity was associated with 10.6-fold (95% confidence interval [CI]: 2.4, 46.2; p = 0.0018) and 7.4-fold (95% CI: 1.3, 41.3; p = 0.023) increased odds of AD dementia relative to NC and MCI, respectively, after adjusting for multiple covariates.Conclusion: Greater nailfold capillary tortuosity was found in participants with AD dementia compared to those with MCI or NC. These data provide preliminary evidence of a systemic microvasculopathy in AD that may be noninvasively and inexpensively evaluated through NVC. [ABSTRACT FROM AUTHOR]- Published
- 2018
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23. Possible Role of Chitin-Like Proteins in the Etiology of Alzheimer's Disease.
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Lomiguen, Christine, Vidal, Luis, Kozlowski, Piotr, Prancan, Arthur, and Stern, Robert
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ETIOLOGY of Alzheimer's disease ,CHITIN ,HYALURONIC acid ,CHITINASE ,GENETICS of Alzheimer's disease ,VERTEBRATE physiology ,PROTEIN metabolism ,ALZHEIMER'S disease ,POLYSACCHARIDES ,TRANSFERASES - Abstract
Chitin is a β-linked straight chain carbohydrate matrix monopolymer prominent in invertebrates, from fungi to arthropods. Surprisingly, chitin is now documented in vertebrates, including humans, a component of vertebrate physiology that has been neglected until now. Chitin levels are elevated in Alzheimer's disease (AD) patients, not only in the central nervous system but also in the cerebrospinal fluid and plasma. Elevated levels of chitin lectin have been reported in patients with AD. Chitinase activity varies widely in the human population. Chitin levels can increase in individuals with intrinsically low chitinase activity. Elevated amounts of chitin can reflect accumulation of the small chitin fragments that remain wherever rapid hyaluronan synthesis occurs. Another source of chitin may be from remote fungal infections. Chitin can be toxic for neurons, and its accumulation may lead to the development of AD. We present new suggestions for animal models and treatment modalities that could prove useful in future research endeavors. An unexpected connection with Gaucher's disease patients and their heterozygote relatives is also identified. These chitin-related mechanisms are novel approaches to AD whose etiology until now has defied explication. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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24. Cerebrospinal fluid tau, Aβ, and sTREM2 in Former National Football League Players: Modeling the relationship between repetitive head impacts, microglial activation, and neurodegeneration.
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Alosco, Michael L., Tripodis, Yorghos, Fritts, Nathan G., Heslegrave, Amanda, Baugh, Christine M., Conneely, Shannon, Mariani, Megan, Martin, Brett M., Frank, Samuel, Mez, Jesse, Stein, Thor D., Cantu, Robert C., McKee, Ann C., Shaw, Leslie M., Trojanowski, John Q., Blennow, Kaj, Zetterberg, Henrik, and Stern, Robert A.
- Abstract
Introduction: Cerebrospinal fluid (CSF) protein analysis may facilitate detection and elucidate mechanisms of neurological consequences from repetitive head impacts (RHI), such as chronic traumatic encephalopathy. We examined CSF concentrations of total tau (t‐tau), phosphorylated tau, and amyloid β1‐42 and their association with RHI in former National Football League (NFL) players. The role of microglial activation (using sTREM2) was examined as a pathogenic mechanism of chronic traumatic encephalopathy. Methods: Sixty‐eight former NFL players and 21 controls underwent lumbar puncture to quantify t‐tau, p‐tau181, amyloid β1‐42, and sTREM2 in the CSF using immunoassays. The cumulative head impact index estimated RHI. Results: No between‐group differences for CSF analytes emerged. In the former NFL players, the cumulative head impact index predicted higher t‐tau concentrations (P =.041), and higher sTREM2 levels were associated with higher t‐tau concentrations (P =.009). Discussion: In this sample of former NFL players, greater RHI and increased microglial activation were associated with higher CSF t‐tau concentrations. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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25. A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology.
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Killiany, Ronald J., Alosco, Michael L., Mez, Jesse, Stern, Robert A., McKee, Ann C., Kowall, Neil W., Sugarman, Michael A., Tripodis, Yorghos, Martin, Brett, Palmisano, Joseph N., Stein, Thor D., DeCarli, Charles, Brett, Martin, Au, Rhoda, and Besser, Lilah M.
- Subjects
CLINICAL pathology ,WHITE matter (Nerve tissue) ,MAGNETIC resonance imaging ,ALZHEIMER'S disease ,NEUROLOGICAL disorders ,BRAIN diseases ,APOLIPOPROTEINS ,BRAIN ,PSYCHOLOGICAL tests ,RESEARCH funding ,LOGISTIC regression analysis ,DISEASE complications - Abstract
Background: White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility.Objective: This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP.Methods: The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy.Results: 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04).Conclusions: This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease. [ABSTRACT FROM AUTHOR]- Published
- 2018
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26. Neuropsychiatric Symptoms and the Diagnostic Stability of Mild Cognitive Impairment.
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Steinberg, Eric G., Sugarman, Michael A., Alosco, Michael L., Stern, Robert A., and Tripodis, Yorghos
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MILD cognitive impairment ,COGNITION disorders ,NEUROBEHAVIORAL disorders ,ALZHEIMER'S disease risk factors ,GERIATRIC Depression Scale ,ALZHEIMER'S disease ,COGNITIVE ability ,PROGNOSIS ,DIAGNOSIS ,LONGITUDINAL method ,NEUROPSYCHOLOGICAL tests ,RESEARCH funding ,TIME ,DISEASE progression - Abstract
Background: Mild cognitive impairment (MCI) is an intermediate diagnosis between normal cognition (NC) and dementia, including Alzheimer's disease (AD) dementia. However, MCI is heterogeneous; many individuals subsequently revert to NC while others remain stable at MCI for several years. Identifying factors associated with this diagnostic instability could assist in defining clinical populations and determining cognitive prognoses.Objective: The current study examined whether neuropsychiatric symptoms could partially account for the temporal instability in cognitive diagnoses.Method: The sample included 6,763 participants from the National Alzheimer's Coordinating Center Uniform Data Set. All participants had NC at baseline, completed at least two follow-up visits (mean duration: 5.5 years), and had no recent neurological conditions. Generalized linear models estimated by generalized estimating equations examined associations between changes in cognitive diagnoses and symptoms on the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Geriatric Depression Scale (GDS-15).Results: 1,121 participants converted from NC to MCI; 324 reverted back to NC and 242 progressed to AD dementia. Higher symptoms on the GDS-15 and circumscribed symptom domains on the NPI-Q were associated with conversion from NC to MCI and a decreased likelihood of reversion from MCI to NC. Individuals with higher symptoms on NPI-Q Hyperactivity and Mood items were more likely to progress to AD dementia.Discussion: The temporal instability of MCI can be partially explained by neuropsychiatric symptoms. Individuals with higher levels of specific symptoms are more likely to progress to AD dementia and less likely to revert to NC. Identification and treatment of these symptoms might support cognitive functioning in older adults. [ABSTRACT FROM AUTHOR]- Published
- 2018
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27. Pramlintide: The Effects of a Single Drug Injection on Blood Phosphatidylcholine Profile for Alzheimer's Disease.
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Qiushan Tao, Haihao Zhu, Xi Chen, Stern, Robert A., Kowall, Neil, Au, Rhoda, Blusztajn, Jan Krzysztof, Wei Qiao Qiu, Tao, Qiushan, Zhu, Haihao, Chen, Xi, Qiu, Wei Qiao, and Alzheimer’s Disease Metabolomics Consortium
- Subjects
ALZHEIMER'S disease treatment ,LECITHIN ,DRUG administration ,INJECTIONS ,LABORATORY mice ,ALZHEIMER'S disease diagnosis ,ALZHEIMER'S disease ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,NERVE tissue proteins ,PEPTIDES ,RESEARCH ,RESEARCH funding ,LOGISTIC regression analysis ,EVALUATION research ,RECEIVER operating characteristic curves ,PANCREATIC hormones - Abstract
Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse models and AD patients. The aim of this study was to examine whether a pramlintide challenge combined with a phosphatidylcholine (PC) profile diagnoses of AD and mild cognitive impairment (MCI) better than PC alone. Non-diabetic subjects with cognitive status were administered a single subcutaneous injection of 60 mcg of pramlintide under fasting condition. A total of 71 PCs, amyloid-β peptide (Aβ), and total tau (t-tau) in plasma at different time points were measured and treated as individual variables. A single injection of pramlintide altered the levels of 7 PCs in the blood, while a pramlintide injection plus food modulated the levels of 10 PCs in the blood (p < 0.05). The levels of 2 PCs in MCI and 12 PCs in AD in the pramlintide challenge were significantly lower than the ones in controls. We found that while some PCs were associated with only Aβ levels, other PCs were associated with both Aβ and t-tau levels. A receiver operating characteristic analysis of the PCs was combined with the Aβ and t-tau data to produce an area under the curve predictive value of 0.9799 between MCI subjects and controls, 0.9794 between AD subjects and controls, and 0.9490 between AD and MCI subjects. A combination of AD biomarkers and a group of PCs post a pramlintide challenge may provide a valuable diagnostic and prognostic test for AD and MCI. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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28. Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer's Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer's Coordinating Center Data Set.
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Alosco, Michael L., Duskina, Jonathan, Besser, Lilah M., Martin, Brett, Chaisson, Christine E., Gunstad, John, Kowall, Neil W., McKee, Ann C., Stern, Robert A., Tripodis, Yorghos, and Duskin, Jonathan
- Subjects
BODY mass index ,CEREBROVASCULAR disease ,ALZHEIMER'S disease ,NEUROLOGICAL disorders ,AUTOPSY - Abstract
The relationship between late-life body mass index (BMI) and Alzheimer's disease (AD) is poorly understood due to the lack of research in samples with autopsy-confirmed AD neuropathology (ADNP). The role of cerebrovascular disease (CVD) in the interplay between late-life BMI and ADNP is unclear. We conducted a retrospective longitudinal investigation and used joint modeling of linear mixed effects to investigate causal relationships among repeated antemortem BMI measurements, CVD (quantified neuropathologically), and ADNP in an autopsy sample of subjects across the AD clinical continuum. The sample included 1,421 subjects from the National Alzheimer's Coordinating Center's Uniform Data Set and Neuropathology Data Set with diagnoses of normal cognition (NC; n = 234), mild cognitive impairment (MCI; n = 201), or AD dementia (n = 986). ADNP was defined as moderate to frequent neuritic plaques and Braak stageIII-VI. Ischemic Injury Scale (IIS) operationalized CVD. Joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score. Subject-specific random intercept for BMI was the predictor for ADNP due to minimal BMI change (p = 0.3028). Analyses controlling for demographic variables and APOE ɛ4 showed lower late-life BMI predicted increased odds of ADNP in the overall sample (p < 0.001), and in subjects with CDR of 0 (p = 0.0021) and 0.5 (p = 0.0012), but not ≥1.0 (p = 0.2012). Although higher IIS predicted greater odds of ADNP (p < 0.0001), BMI did not predict IIS (p = 0.2814). The current findings confirm lower late-life BMI confers increased odds for ADNP. Lower late-life BMI may be a preclinical indicator of underlying ADNP. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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29. Mini Mental State Examination and Logical Memory scores for entry into Alzheimer's disease trials.
- Author
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Chapman, Kimberly R., Bing-Canar, Hanaan, Alosco, Michael L., Steinberg, Eric G., Martin, Brett, Chaisson, Christine, Kowall, Neil, Tripodis, Yorghos, and Stern, Robert A.
- Subjects
ALZHEIMER'S disease ,MINI-Mental State Examination ,CLINICAL trials ,MILD cognitive impairment ,NEURODEGENERATION - Abstract
Background: Specific cutoff scores on the Mini Mental State Examination (MMSE) and the Logical Memory (LM) test are used to determine inclusion in Alzheimer's disease (AD) clinical trials and diagnostic studies. These screening measures have known psychometric limitations, but no study has examined the diagnostic accuracy of the cutoff scores used to determine entry into AD clinical trials and diagnostic studies. Methods: ClinicalTrials.gov entries were reviewed for phases II and III active and recruiting AD studies using the MMSE and LM for inclusion. The diagnostic accuracy of MMSE and LM-II cutoffs used in AD trials and diagnostic studies was examined using 23,438 subjects with normal cognition, mild cognitive impairment (MCI), and AD dementia derived from the National Alzheimer's Coordinating Center database. Results: MMSE and LM cutoffs used in current AD clinical trials and diagnostic studies had limited diagnostic accuracy, particularly for distinguishing between normal cognition and MCI, and MCI from AD dementia. The MMSE poorly discriminated dementia stage. Conclusions: The MMSE and LM may result in inappropriate subject enrollment in large-scale, multicenter studies designed to develop therapeutics and diagnostic methods for AD. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. Retinal blood flow in mild cognitive impairment and Alzheimer's disease
- Author
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Feke, Gilbert T., Hyman, Bradley T., Stern, Robert A., and Pasquale, Louis R.
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Mild cognitive impairment ,Alzheimer's disease ,Retinal venous blood column diameter ,Retinal blood speed ,Retinal blood flow - Abstract
Background: Patients with Alzheimer's disease (AD) demonstrate the narrowing of retinal veins and decreased retinal venous blood flow compared with control subjects. We assessed whether these abnormalities are present in patients with mild cognitive impairment (MCI). Methods: After the determination of the global clinical dementia rating, 52 subjects (10 AD, 21 MCI, and 21 normal controls) underwent retinal hemodynamic profiling. Blood column diameter, blood speed, and blood flow were measured in a major temporal retinal vein using retinal laser Doppler flowmetry. In addition, peripapillary retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography. Results: Blood column diameter in AD was narrower than in both MCI (P = .004) and controls (P = .002). However, blood speed in both AD (P = .024) and MCI (P = .005) was lower than in controls. As a result, the differences in blood flow between AD and MCI (P = .036), AD and controls (P < .0001), and MCI and controls (P = .009) were significant. Although there were no differences in RNFL thickness among the groups, blood flow was correlated (P = .047) with superior RNFL thickness in the AD group, but not in the MCI (P = .40) or control (P = .84) groups. Conclusions: Retinal blood flow in MCI is intermediate between what is measured in control subjects and in AD patients. Our findings suggest that blood flow abnormalities may precede the neurodegeneration in AD.
- Published
- 2015
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31. Lack of Association of Informant-Reported Traumatic Brain Injury and Chronic Traumatic Encephalopathy.
- Author
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Culhane, Julia E., Jackson, Colleen E., Tripodis, Yorghos, Nowinski, Christopher J., Dams-O'Connor, Kristen, Pettway, Erika, Uretsky, Madeline, Abdolmohammadi, Bobak, Nair, Evan, Martin, Brett, Palmisano, Joseph, Katz, Douglas I., Dwyer, Brigid, Daneshvar, Daniel H., Goldstein, Lee E., Kowall, Neil W., Cantu, Robert C., Stern, Robert A., Huber, Bertrand Russell, and Crary, John F.
- Subjects
- *
CHRONIC traumatic encephalopathy , *BRAIN injuries , *HEAD injuries , *LOSS of consciousness , *ALZHEIMER'S disease - Abstract
Repetitive head impacts (RHIs) from football are associated with the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). It is unclear whether a history of traumatic brain injury (TBI) is sufficient to precipitate CTE neuropathology. We examined the association between TBI and CTE neuropathology in 580 deceased individuals exposed to RHIs from football. TBI history was assessed using a modified version of the Ohio State University TBI Identification Method Short Form administered to informants. There were 22 donors who had no TBI, 213 who had at least one TBI without loss of consciousness (LOC), 345 who had TBI with LOC, and, of those with a history of TBI with LOC, 36 who had at least one moderate-to-severe TBI (msTBI, LOC >30 min). CTE neuropathology was diagnosed in 405. There was no association between CTE neuropathology status or severity and TBI with LOC (odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.64–1.41; OR = 1.22, 95% CI = 0.71–2.09) or msTBI (OR = 0.70, 95% CI = 0.33–1.50; OR = 1.01, 95% CI = 0.30–3.41). There were no associations with other neurodegenerative or cerebrovascular pathologies examined. TBI with LOC and msTBI were not associated with CTE neuropathology in this sample of brain donors exposed to RHIs from American football. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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32. Independent effects of white matter hyperintensities on cognitive, neuropsychiatric, and functional decline: a longitudinal investigation using the National Alzheimer's Coordinating Center Uniform Data Set.
- Author
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Puzo, Christian, Labriola, Caroline, Sugarman, Michael A., Tripodis, Yorghos, Martin, Brett, Palmisano, Joseph N., Steinberg, Eric G., Stein, Thor D., Kowall, Neil W., McKee, Ann C., Mez, Jesse, Killiany, Ronald J., Stern, Robert A., and Alosco, Michael L.
- Subjects
CEREBRAL small vessel diseases ,MILD cognitive impairment ,ALZHEIMER'S disease ,NEUROPSYCHOLOGICAL tests ,WHITE matter (Nerve tissue) ,COGNITION - Abstract
Background: Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer's disease, particularly in the early disease stages. This study leveraged the National Alzheimer's Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition. Methods: The sample included 465 participants from the National Alzheimer's Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological test battery within 1 year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer's disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD. Results: Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up = 5 years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ε4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p < 0.01), Digit Symbol Coding (p < 0.01), Logical Memory Immediate Recall (p = 0.02), Trail Making A (p < 0.01), and Semantic Fluency (p < 0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p < 0.01) and Geriatric Depression Scale-15 scores (p = 0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia. Conclusions: In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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33. A longitudinal examination of plasma neurofilament light and total tau for the clinical detection and monitoring of Alzheimer's disease.
- Author
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Sugarman, Michael A., Zetterberg, Henrik, Blennow, Kaj, Tripodis, Yorghos, McKee, Ann C., Stein, Thor D., Martin, Brett, Palmisano, Joseph N., Steinberg, Eric G., Simkin, Irene, Budson, Andrew E., Killiany, Ronald, O'Connor, Maureen K., Au, Rhoda, Qiu, Wendy Wei Qiao, Goldstein, Lee E., Kowall, Neil W., Mez, Jesse, Stern, Robert A., and Alosco, Michael L.
- Subjects
- *
ALZHEIMER'S disease , *CYTOPLASMIC filaments , *MILD cognitive impairment , *NEUROPSYCHOLOGICAL tests , *COGNITIVE testing - Abstract
We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 participants (238, normal cognition [NC]; 185, mild cognitive impairment [MCI]; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79]), and correlated with all neuropsychological tests (r 's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau. • Baseline plasma neurofilament light was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition. • Baseline plasma neurofilament light was associated with baseline cognitive test score and predicted subsequent decline but did not predict diagnostic conversion. • Baseline plasma total tau was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition. • There were no statistically significant effects for baseline plasma total tau on cognitive decline or diagnostic conversion. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
34. Overview of the Reserve Concept in the Context of Cognitive Aging
- Author
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Sunderaraman, Preeti, Stern, Yaakov, Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
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35. Alzheimer’s Disease
- Author
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Rentz, Dorene M., Orlovsky, Irina, Kilpatrick, Emily, Papp, Kathryn V., Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
- View/download PDF
36. Genetics of Adult Cognitive Disorders
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Evers, Laney, Verscaj, Courtney, Mez, Jesse, Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
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37. Normal Cognitive and Brain Aging
- Author
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Leal, Stephanie L., Yassa, Michael A., Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
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38. Considerations for Translational Research in the Study of Adult Cognitive Disorders
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Franz, Erich S., Chancellor, Sarah E., Goldstein, Lee E., Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
- View/download PDF
39. Issues of Diversity in Cognitive Aging: A Focus on Older African Americans
- Author
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Barnes, Lisa L., Alosco, Michael L., book editor, and Stern, Robert A., book editor
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- 2019
- Full Text
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40. The Oxford Handbook of Adult Cognitive Disorders
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Alosco, Michael L., editor and Stern, Robert A., editor
- Published
- 2019
- Full Text
- View/download PDF
41. Cognition, Aging, and the Development of Dementia in Down Syndrome
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Caban-Holt, Allison, Powell, David K., Anderson-Mooney, Amelia J., Robertson, William, Lightner, Donita, Schmitt, Frederick A., Head, Elizabeth, Alosco, Michael L., book editor, and Stern, Robert A., book editor
- Published
- 2019
- Full Text
- View/download PDF
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