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Article ; Online: Environmental exposures and the risk for Alzheimer disease: can we identify the smoking guns?

Dekosky, Steven T / Gandy, Sam

2014 Volume 71, Issue 3, Page(s) 273–275

MeSH term(s)	Alzheimer Disease/chemically induced ; Apolipoprotein E4/genetics ; Dichlorodiphenyl Dichloroethylene/adverse effects ; Female ; Humans ; Insecticides/adverse effects ; Male
Chemical Substances	Apolipoprotein E4 ; Insecticides ; Dichlorodiphenyl Dichloroethylene (4M7FS82U08)
Language	English
Publishing date	2014-01-29
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2013.6031
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Article ; Online: Acute and chronic effects of single dose memantine after controlled cortical impact injury in adult rats.

Abrahamson, Eric E / Poloyac, Samuel M / Dixon, C Edward / Dekosky, Steven T / Ikonomovic, Milos D

Restorative neurology and neuroscience

2019 Volume 37, Issue 3, Page(s) 245–263

Abstract: Background: Altered glutamatergic neurotransmission after traumatic brain injury (TBI) contributes to excitotoxic cell damage and death. Prevention or suppression of such changes is a desirable goal for treatment of TBI. Memantine (3,5-dimethyl-1- ... ...

Abstract	Background: Altered glutamatergic neurotransmission after traumatic brain injury (TBI) contributes to excitotoxic cell damage and death. Prevention or suppression of such changes is a desirable goal for treatment of TBI. Memantine (3,5-dimethyl-1-adamantanamine), an uncompetitive NMDA receptor antagonist with voltage-dependent open channel blocking kinetics, was reported to be neuroprotective in preclinical models of excitotoxicity, brain ischemia, and in TBI when administered prophylactically, immediately, or within minutes after injury. Methods: The current study examined effects of memantine administered by single intraperitoneal injection to adult male rats at a more clinically relevant delay of one hour after moderate-severe controlled cortical impact (CCI) injury or sham surgery. Histopathology was assessed on days 1, 7, 21, and 90, vestibulomotor function (beam balance and beam walk) was assessed on days 1-5 and 71-75, and spatial memory (Morris water maze test, MWM) was assessed on days 14-21 and 83-90 after CCI injury or sham surgery. Results: When administered at 10 mg/kg, but not 2.5 or 5 mg/kg, memantine preserved cortical tissue and reduced neuronal degeneration 1 day after injury, and attenuated loss of synaptophysin immunoreactivity in the hippocampus 7 days after injury. No effects of 10 mg/kg memantine were observed on histopathology at 21 and 90 days after CCI injury or sham surgery, or on vestibulomotor function and spatial memory acquisition assessed during any of the testing periods. However, 10 mg/kg memantine resulted in trends for improved search strategy in the MWM memory retention probe trial. Conclusions: Administration of memantine at a clinically-relevant delay after moderate-severe CCI injury has beneficial effects on acute outcomes, while more significant improvement on subacute and chronic outcomes may require repeated drug administration or its combination with another therapy.
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; Brain Injuries, Traumatic/drug therapy ; Cerebral Cortex/drug effects ; Cerebral Cortex/injuries ; Disease Models, Animal ; Excitatory Amino Acid Antagonists/administration & dosage ; Excitatory Amino Acid Antagonists/pharmacology ; Hippocampus/drug effects ; Male ; Memantine/administration & dosage ; Memantine/pharmacology ; Motor Activity/drug effects ; Nerve Degeneration/prevention & control ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Spatial Memory/drug effects ; Time Factors ; Vestibule, Labyrinth/drug effects
Chemical Substances	Excitatory Amino Acid Antagonists ; Receptors, N-Methyl-D-Aspartate ; Memantine (W8O17SJF3T)
Language	English
Publishing date	2019-06-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1017098-4
ISSN	1878-3627 ; 0922-6028
ISSN (online)	1878-3627
ISSN	0922-6028
DOI	10.3233/RNN-190909
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Zs.A 2792: Show issues

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Article ; Online: APOE ε4 status and traumatic brain injury on the gridiron or the battlefield.

Gandy, Sam / Dekosky, Steven T

Science translational medicine

2012 Volume 4, Issue 134, Page(s) 134ed4

MeSH term(s)	Alleles ; Apolipoproteins E/genetics ; Brain Injuries/genetics ; Brain Injury, Chronic ; Cohort Studies ; Football ; Genotyping Techniques ; Health Surveys ; Humans ; Military Personnel ; Schools
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2012-05-16
Publishing country	United States
Document type	Editorial
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.3004274
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Zs.A 6941: Show issues

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Article: Baseline Neuroimaging Predicts Decline to Dementia From Amnestic Mild Cognitive Impairment.

Gullett, Joseph M / Albizu, Alejandro / Fang, Ruogu / Loewenstein, David A / Duara, Ranjan / Rosselli, Monica / Armstrong, Melissa J / Rundek, Tatjana / Hausman, Hanna K / Dekosky, Steven T / Woods, Adam J / Cohen, Ronald A

Frontiers in aging neuroscience

2021 Volume 13, Page(s) 758298

Abstract: Background and Objectives: ...

Abstract	Background and Objectives:
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.758298
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Article: Clinical symptoms in Alzheimer's disease.

López, Oscar L / Dekosky, Steven T

Handbook of clinical neurology

2008 Volume 89, Page(s) 207–216

MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Basal Ganglia Diseases/diagnosis ; Basal Ganglia Diseases/etiology ; Behavioral Symptoms/diagnosis ; Behavioral Symptoms/etiology ; Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Cognition Disorders/pathology ; Humans ; Lewy Bodies/metabolism ; Lewy Bodies/pathology ; Nervous System Diseases/diagnosis ; Nervous System Diseases/etiology
Language	English
Publishing date	2008
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	0072-9752
ISSN	0072-9752
DOI	10.1016/S0072-9752(07)01219-5
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Article ; Online: The expanding role of genetics in the lewy body diseases: the glucocerebrosidase gene.

Leverenz, James B / Lopez, Oscar L / Dekosky, Steven T

Archives of neurology

2009 Volume 66, Issue 5, Page(s) 555–556

MeSH term(s)	DNA Mutational Analysis ; Ethnic Groups/genetics ; Genetic Markers/genetics ; Genetic Predisposition to Disease/genetics ; Genetic Testing ; Glucosylceramidase/genetics ; Humans ; Lewy Body Disease/enzymology ; Lewy Body Disease/genetics ; Lewy Body Disease/physiopathology ; Mutation/genetics ; Parkinson Disease/enzymology ; Parkinson Disease/genetics ; Parkinson Disease/physiopathology
Chemical Substances	Genetic Markers ; Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2009-05-11
Publishing country	United States
Document type	Comment ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80049-1
ISSN	1538-3687 ; 0003-9942
ISSN (online)	1538-3687
ISSN	0003-9942
DOI	10.1001/archneurol.2009.61
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Ui II Zs.191: Show issues

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Article: Recollection and familiarity in amnestic mild cognitive impairment: a global decline in recognition memory.

Wolk, David A / Signoff, Eric D / Dekosky, Steven T

Neuropsychologia

2008 Volume 46, Issue 7, Page(s) 1965–1978

Abstract: Despite memory failures being a central feature of amnestic mild cognitive impairment (a-MCI), there is limited research into the nature of the memory impairment associated with this condition. A further understanding could lead to refinement of criteria ...

Abstract	Despite memory failures being a central feature of amnestic mild cognitive impairment (a-MCI), there is limited research into the nature of the memory impairment associated with this condition. A further understanding could lead to refinement of criteria needed to qualify for this designation and aid in prediction of who will progress to development of clinical Alzheimer's disease. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. The present study sought to evaluate recognition memory in a-MCI in the framework of the dual process model. Patients with a-MCI and age- and education-matched controls were tested on three memory paradigms. Two paradigms were modifications of the process-dissociation procedure in which recollection required either memory of word-pair associations (associative) or the font color of words at study (featural). A final paradigm utilized the task-dissociation methodology comparing performance for item and visual spatial source memory. All three tasks revealed that familiarity was impaired to at least the same extent as recollection. As familiarity is thought to be spared in normal aging, its measurement may provide a relatively specific marker for the early pathological changes of Alzheimer's disease.
MeSH term(s)	Aged ; Aging/physiology ; Alzheimer Disease/diagnosis ; Alzheimer Disease/physiopathology ; Amnesia/diagnosis ; Amnesia/physiopathology ; Cognition Disorders/diagnosis ; Cognition Disorders/physiopathology ; Color Perception/physiology ; Control Groups ; Entorhinal Cortex/physiopathology ; Female ; Humans ; Judgment ; Male ; Memory Disorders/diagnosis ; Memory Disorders/physiopathology ; Mental Recall/physiology ; Models, Biological ; Neuropsychological Tests/statistics & numerical data ; Practice, Psychological ; Prognosis ; Recognition, Psychology/physiology ; Task Performance and Analysis ; Visual Perception/physiology ; Word Association Tests/statistics & numerical data
Language	English
Publishing date	2008-02-02
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207151-4
ISSN	1873-3514 ; 0028-3932
ISSN (online)	1873-3514
ISSN	0028-3932
DOI	10.1016/j.neuropsychologia.2008.01.017
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Zs.A 524: Show issues

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Article ; Online: Cerebral blood flow changes after brain injury in human amyloid-beta knock-in mice.

Abrahamson, Eric E / Foley, Lesley M / Dekosky, Steven T / Hitchens, T Kevin / Ho, Chien / Kochanek, Patrick M / Ikonomovic, Milos D

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2013 Volume 33, Issue 6, Page(s) 826–833

Abstract: Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer's disease (AD). Increased brain concentrations of amyloid-β (Aβ) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising ... ...

Abstract	Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer's disease (AD). Increased brain concentrations of amyloid-β (Aβ) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising therapeutic targets. We used arterial spin-labeling magnetic resonance imaging to examine if CBF changes after TBI are influenced by human Aβ and amenable to simvastatin therapy. CBF was measured 3 days and 3 weeks after controlled cortical impact (CCI) injury in transgenic human Aβ-expressing APP(NLh/NLh) mice compared to murine Aβ-expressing C57Bl/6J wild types. Compared to uninjured littermates, CBF was reduced in the cortex of the injured hemisphere in both Aβ transgenics and wild types; deficits were more pronounced in the transgenic group, which exhibited injury-induced increased concentrations of human Aβ. In the hemisphere contralateral to CCI, CBF levels were stable in Aβ transgenic mice but increased in wild-type mice, both relative to uninjured littermates. Post-injury treatment of Aβ transgenic mice with simvastatin lowered brain Aβ concentrations, attenuated deficits in CBF ipsilateral to injury, restored hyperemia contralateral to injury, and reduced brain tissue loss. Future studies examining long-term effects of simvastatin therapy on CBF and chronic neurodegenerative changes after TBI are warranted.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/etiology ; Alzheimer Disease/genetics ; Amyloid beta-Peptides/analysis ; Amyloid beta-Peptides/genetics ; Animals ; Anticholesteremic Agents/therapeutic use ; Brain/blood supply ; Brain/drug effects ; Brain/physiopathology ; Brain Injuries/complications ; Brain Injuries/drug therapy ; Brain Injuries/genetics ; Brain Injuries/physiopathology ; Cerebrovascular Circulation/drug effects ; Gene Knock-In Techniques ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Risk Factors ; Simvastatin/therapeutic use
Chemical Substances	Amyloid beta-Peptides ; Anticholesteremic Agents ; Simvastatin (AGG2FN16EV)
Language	English
Publishing date	2013-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1038/jcbfm.2013.24
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Zs.A 1663: Show issues

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Article ; Online: Gray matter atrophy associated with extrapyramidal signs in the Lewy body variant of Alzheimer's disease.

Choi, Seong Hye / Olabarrieta, Mikel / Lopez, Oscar L / Maruca, Victoria / Dekosky, Steven T / Hamilton, Ronald L / Becker, James T

Journal of Alzheimer's disease : JAD

2012 Volume 32, Issue 4, Page(s) 1043–1049

Abstract: Up to 60% of the patients with Alzheimer's disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has ... ...

Abstract	Up to 60% of the patients with Alzheimer's disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has not been studied in the LB variant of AD using structural magnetic resonance imaging (MRI). The purpose of this study was to determine the relationship between patterns of brain atrophy and clinical EPS in patients with pathologically confirmed AD. We compared gray matter structure using voxel-based morphometry in 29 Definite AD cases, 16 (55%) of whom also had LBs identified with α-synuclein immunohistochemistry. Multivariate models analyzed brain volume at a voxel level accounting for subject group, Mini-Mental State Examination (MMSE), EPS, total brain volume, and the time from MRI scan to death. There was no significant difference in gray matter volume in the Definite AD patients as a function of LB. There was a significant association between gray matter volumes and the MMSE in AD patients, both with and without LBs. There was a significant correlation between gray matter volume and EPS only in the group of AD patients with LBs, and not in those with pure AD. These findings suggest that that the etiology of EPS in patients with the LB variant of AD is associated with neuronal loss in the nigrostriatal tracts. By contrast, the source of the EPS in AD alone appears to be less well localized.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Alzheimer Disease/pathology ; Atrophy ; Basal Ganglia Diseases/epidemiology ; Basal Ganglia Diseases/pathology ; Cerebral Cortex/pathology ; Female ; Humans ; Lewy Body Disease/epidemiology ; Lewy Body Disease/pathology ; Male
Language	English
Publishing date	2012-08-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-2012-121108
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Zs.A 6084: Show issues

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Article: Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset.

Eror, Elise A / Lopez, Oscar L / Dekosky, Steven T / Sweet, Robert A

Biological psychiatry

2005 Volume 58, Issue 4, Page(s) 325–330

Abstract: Background: Recent findings have demonstrated the familiality of psychotic symptoms occurring during Alzheimer disease (AD with psychosis, AD+P), particularly for subjects with multiple psychotic symptoms. We have proposed a model in which genes that ... ...

Abstract	Background: Recent findings have demonstrated the familiality of psychotic symptoms occurring during Alzheimer disease (AD with psychosis, AD+P), particularly for subjects with multiple psychotic symptoms. We have proposed a model in which genes that confer a small risk for psychosis interact with neurodegenerative illness to yield manifest psychotic symptoms during AD. One prediction of this model would be that AD+P subjects would have evidence of increased degrees of subsyndromal psychosis before AD onset. Methods: We used the psychosis (positive symptoms) and psychotic personality disorder sections (paranoid, schizoid, and schizotypal) of the Family Interview for Genetic Studies (FIGS) to interview the primary caregivers of AD subjects. Caregivers were specifically instructed to answer questions with regard to the subject's behavior before AD onset. Interviewers were blind to presence of psychosis during AD. Subjects were grouped by whether they had at least one or had multiple psychotic symptoms during AD. Results: Scores on the FIGS subscales were generally low, reflecting a low frequency of endorsement of psychotic symptoms before AD. There was a trend for the schizotypal scores to be elevated in the AD+P group, which was highly significant in the AD+P group with multiple psychotic symptoms. There was no significant association of paranoid or schizoid scores with either group. Conclusions: Although limited by small sample size and retrospective design, these data are novel in that they indicate an association of subsyndromal psychotic symptoms before AD onset with psychosis in AD. Subsyndromal psychosis might be useful for classifying AD+P families for genetic mapping studies. Prospective confirmation is required.
MeSH term(s)	Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/complications ; Alzheimer Disease/psychology ; Chi-Square Distribution ; Dementia/etiology ; Dementia/psychology ; Demography ; Female ; Humans ; Interview, Psychological/methods ; Male ; Middle Aged ; Models, Genetic ; Predictive Value of Tests ; Psychotic Disorders/complications ; Psychotic Disorders/psychology ; Schizotypal Personality Disorder/physiopathology ; Schizotypal Personality Disorder/psychology ; Severity of Illness Index
Language	English
Publishing date	2005-08-15
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2005.04.017
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