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Article ; Online: Side-by-side comparison of published small molecule inhibitors against thapsigargin-induced store-operated Ca2+ entry in HEK293 cells.

Norman, Katherine / Hemmings, Karen E / Shawer, Heba / Appleby, Hollie L / Burnett, Alan J / Hamzah, Nurasyikin / Gosain, Rajendra / Woodhouse, Emily M / Beech, David J / Foster, Richard / Bailey, Marc A

PloS one

2024 Volume 19, Issue 1, Page(s) e0296065

Abstract: Calcium (Ca2+) is a key second messenger in eukaryotes, with store-operated Ca2+ entry (SOCE) being the main source of Ca2+ influx into non-excitable cells. ORAI1 is a highly Ca2+-selective plasma membrane channel that encodes SOCE. It is ubiquitously ... ...

Abstract	Calcium (Ca2+) is a key second messenger in eukaryotes, with store-operated Ca2+ entry (SOCE) being the main source of Ca2+ influx into non-excitable cells. ORAI1 is a highly Ca2+-selective plasma membrane channel that encodes SOCE. It is ubiquitously expressed in mammals and has been implicated in numerous diseases, including cardiovascular disease and cancer. A number of small molecules have been identified as inhibitors of SOCE with a variety of potential therapeutic uses proposed and validated in vitro and in vivo. These encompass both nonselective Ca2+ channel inhibitors and targeted selective inhibitors of SOCE. Inhibition of SOCE can be quantified both directly and indirectly with a variety of assay setups, making an accurate comparison of the activity of different SOCE inhibitors challenging. We have used a fluorescence based Ca2+ addback assay in native HEK293 cells to generate dose-response data for many published SOCE inhibitors. We were able to directly compare potency. Most compounds were validated with only minor and expected variations in potency, but some were not. This could be due to differences in assay setup relating to the mechanism of action of the inhibitors and highlights the value of a singular approach to compare these compounds, as well as the general need for biorthogonal validation of novel bioactive compounds. The compounds observed to be the most potent against SOCE in our study were: 7-azaindole 14d (12), JPIII (17), Synta-66 (6), Pyr 3 (5), GSK5503A (8), CM4620 (14) and RO2959 (7). These represent the most promising candidates for future development of SOCE inhibitors for therapeutic use.
MeSH term(s)	Animals ; Humans ; Calcium ; HEK293 Cells ; Thapsigargin ; Biological Assay ; Calcium, Dietary ; HIV Fusion Inhibitors ; Mammals
Chemical Substances	Calcium (SY7Q814VUP) ; Thapsigargin (67526-95-8) ; Calcium, Dietary ; HIV Fusion Inhibitors
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0296065
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: 18

Minoshima, Satoshi / Cross, Donna / Thientunyakit, Tanyaluck / Foster, Norman L / Drzezga, Alexander

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2022 Volume 63, Issue Suppl 1, Page(s) 2S–12S

Abstract: Since the invention ... ...

Abstract	Since the invention of
MeSH term(s)	Aged ; Alzheimer Disease/metabolism ; Fluorodeoxyglucose F18 ; Frontotemporal Dementia/diagnostic imaging ; Glucose ; Humans ; Neurodegenerative Diseases/diagnostic imaging ; Positron-Emission Tomography/methods
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.121.263194
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Article ; Online: Evaluating the Impact of Cochlear Implantation on Cognitive Function in Older Adults.

Gurgel, Richard K / Duff, Kevin / Foster, Norman L / Urano, Kaitlynn A / deTorres, Alvin

The Laryngoscope

2021 Volume 132 Suppl 7, Page(s) S1–S15

Abstract: ... impairment (MMSE ≤ 24) to 24 participants with normal cognition (MMSE ≥ 25). In this subgroup analysis ... to cochlear implantation, the cognitive benefits were even greater than in subjects with normal cognition.: Level ...

Abstract	Objectives/hypothesis: We hypothesize that treating hearing loss through cochlear implantation in older adults will improve cognitive function. Study design: Prospective, interventional study. Methods: Thirty-seven participants aged 65 years and older who met criteria for cochlear implantation were enrolled. Subjects underwent preoperative cognitive testing with a novel arrangement of standard neuropsychological tests, including tests of general cognition and mood (Mini-Mental Status Exam [MMSE]), tests of verbally based stimuli and responses (Digit Span, Stroop, Hopkins Verbal Learning Test-Revised [HVLT-R], Hayling Sentence Completion), and comparable visually based tests (Spatial Span, d2 Test of Attention, Brief Visuospatial Memory Test [BVMT], Trails A and B). Testing was repeated 12 months postoperatively. Results: One year postoperatively, subjects showed a statistically significant improvement in hearing and on the following tests of cognitive function: concentration performance of the d2 Test of Attention, Hayling Sentence Completion Test, HVLT-R (total and delayed recall), Spatial Span (backward), and Stroop Color Word Test. A subgroup analysis was performed comparing 13 participants with preoperative cognitive impairment (MMSE ≤ 24) to 24 participants with normal cognition (MMSE ≥ 25). In this subgroup analysis, a greater magnitude of improvement was seen in those with impaired cognition, with statistically significant improvement in Digit Span (scaled score), Stroop Word (T-score), Stroop Color-Word (residual and T-score), HVLT-R, and Hayling (overall). All verbally based test scores improved, and 75% of the visually based test scores improved. Conclusions: This study demonstrates the cognitive benefits of cochlear implantation in older adults 1 year after surgery. For older adults with cognitive impairment prior to cochlear implantation, the cognitive benefits were even greater than in subjects with normal cognition. Level of evidence: 3, nonrandomized controlled cohort Laryngoscope, 132:S1-S15, 2022.
MeSH term(s)	Aged ; Cochlear Implantation ; Cognition ; Hearing Loss ; Humans ; Neuropsychological Tests ; Prospective Studies
Language	English
Publishing date	2021-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.29933
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Article ; Online: Overall and sex-specific risk factors for subjective cognitive decline: findings from the 2015-2018 Behavioral Risk Factor Surveillance System Survey.

Schliep, Karen C / Barbeau, William A / Lynch, Kristine E / Sorweid, Michelle K / Varner, Michael W / Foster, Norman L / Qeadan, Fares

Biology of sex differences

2022 Volume 13, Issue 1, Page(s) 16

Abstract: Background: Prior research indicates that at least 35% of Alzheimer's disease and related dementia risk may be amenable to prevention. Subjective cognitive decline is often the first indication of preclinical dementia, with the risk of subsequent ... ...

Abstract	Background: Prior research indicates that at least 35% of Alzheimer's disease and related dementia risk may be amenable to prevention. Subjective cognitive decline is often the first indication of preclinical dementia, with the risk of subsequent Alzheimer's disease in such individuals being greater in women than men. We wished to understand how modifiable factors are associated with subjective cognitive decline, and whether differences exist by sex. Methods: Data were collected from men and women (45 years and older) who completed the U.S. Behavioral Risk Factor Surveillance System Cognitive Decline Module (2015-2018), n = 216,838. We calculated population-attributable fractions for subjective cognitive decline, stratified by sex, of the following factors: limited education, deafness, social isolation, depression, smoking, physical inactivity, obesity, hypertension, and diabetes. Our models were adjusted for age, race, income, employment, marital and Veteran status, and accounted for communality among risk factors. Results: The final study sample included more women (53.7%) than men, but both had a similar prevalence of subjective cognitive decline (10.6% of women versus 11.2% of men). Women and men had nearly equivalent overall population-attributable fractions to explain subjective cognitive decline (39.7% for women versus 41.3% for men). The top three contributing risk factors were social isolation, depression, and hypertension, which explained three-quarters of the overall population-attributable fraction. Conclusions: While we did not identify any differences in modifiable factors between men and women contributing to subjective cognitive decline, other factors including reproductive or endocrinological health history or biological factors that interact with sex to modify risk warrant further research.
MeSH term(s)	Alzheimer Disease ; Behavioral Risk Factor Surveillance System ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/psychology ; Female ; Humans ; Hypertension/epidemiology ; Male ; Risk Factors
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2587352-0
ISSN	2042-6410 ; 2042-6410
ISSN (online)	2042-6410
ISSN	2042-6410
DOI	10.1186/s13293-022-00425-3
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Article ; Online: Overall and sex-specific risk factors for subjective cognitive decline

Karen C. Schliep / William A. Barbeau / Kristine E. Lynch / Michelle K. Sorweid / Michael W. Varner / Norman L. Foster / Fares Qeadan

Biology of Sex Differences, Vol 13, Iss 1, Pp 1-

findings from the 2015–2018 Behavioral Risk Factor Surveillance System Survey

2022 Volume 14

Abstract: Highlights Subjective Cognitive Decline (SCD) is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias. While there is no current cure for dementia, research indicates that at least 35% of dementia risk may be modifiable by ...

Abstract	Highlights Subjective Cognitive Decline (SCD) is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias. While there is no current cure for dementia, research indicates that at least 35% of dementia risk may be modifiable by decreasing exposures years or even decades before cognitive decline becomes clinically evident. Prior research has shown that the risk of dementia in individuals with cognitive impairment is higher in women than in men, as is the overall risk of dementia. Among a nationally representative population of over 200,000 adults, ages 45 years and older, SCD prevalence was 11% for both women and men. Women and men also had nearly equivalent overall population-attributable fractions to explain subjective cognitive decline (39.7% for women versus 41.3% for men). The top three contributing risk factors for both women and men were social isolation, depression, and hypertension, which explained three-quarters of the overall population-attributable fraction.
Keywords	Subjective cognitive decline ; Dementia ; Cognitive dysfunction ; Behavioral Risk Factor Surveillance System ; Risk factors ; Sex factors ; Medicine ; R ; Physiology ; QP1-981
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article: A new framework for the diagnosis of Alzheimer's disease.

Foster, Norman L

The Lancet. Neurology

2007 Volume 6, Issue 8, Page(s) 667–669

MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Dementia/diagnosis ; Dementia/etiology ; Disease Progression ; Humans
Language	English
Publishing date	2007-08
Publishing country	England
Document type	Comment ; Letter
ZDB-ID	2081241-3
ISSN	1474-4422
ISSN	1474-4422
DOI	10.1016/S1474-4422(07)70179-5
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Article: Strategies for using molecular neuroimaging in dementia.

Foster, Norman L

Handbook of clinical neurology

2008 Volume 89, Page(s) 87–95

MeSH term(s)	Brain/diagnostic imaging ; Brain/metabolism ; Brain/pathology ; Brain Mapping ; Dementia/diagnostic imaging ; Dementia/metabolism ; Dementia/pathology ; Diagnostic Imaging/classification ; Diagnostic Imaging/methods ; Humans ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; Tomography, Emission-Computed, Single-Photon/methods
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)01207-9
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Article: Hypertensive disorders of pregnancy and subsequent risk of Alzheimer's disease and other dementias.

Schliep, Karen C / Shaaban, C Elizabeth / Meeks, Huong / Fraser, Alison / Smith, Ken R / Majersik, Jennifer J / Foster, Norman L / Wactawski-Wende, Jean / Østbye, Truls / Tschanz, JoAnn / Padbury, James F / Sharma, Surrendra / Zhang, Yue / Facelli, Julio C / Abdelrahman, C Samir / Theilen, Lauren / Varner, Michael W

Alzheimer's & dementia (Amsterdam, Netherlands)

2023 Volume 15, Issue 2, Page(s) e12443

Abstract: Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored.: Methods: Using the Utah Population Database, we ...

Abstract	Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored. Methods: Using the Utah Population Database, we performed an 80-year retrospective cohort study of 59,668 parous women. Results: Women with, versus without, HDP, had a 1.37 higher risk of all-cause dementia (95% confidence interval [CI]: 1.26, 1.50) after adjustment for maternal age at index birth, birth year, and parity. HDP was associated with a 1.64 higher risk of vascular dementia (95% CI: 1.19, 2.26) and 1.49 higher risk of other dementia (95% CI: 1.34, 1.65) but not Alzheimer's disease dementia (adjusted hazard ratio = 1.04; 95% CI: 0.87, 1.24). Gestational hypertension and preeclampsia/eclampsia showed similar increased dementia risk. Nine mid-life cardiometabolic and mental health conditions explained 61% of HDP's effect on subsequent dementia risk. Discussion: Improved HDP and mid-life care could reduce the risk of dementia.
Language	English
Publishing date	2023-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12443
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Article ; Online: Does Frailty or Age Increase the Risk of Postoperative Complications Following Cochlear Implantation?

Gordon, Steven A / Aylward, Alana / Patel, Neil S / Bowers, Christian / Presson, Angela P / Smith, Ken R / Foster, Norman L / Gurgel, Richard K

OTO open

2021 Volume 5, Issue 3, Page(s) 2473974X211044084

Abstract: Objective: To evaluate whether frailty or age increases the risk of postoperative complications following cochlear implant (CI) surgery.: Study design: Retrospective cohort study.: Setting: Tertiary academic center.: Methods: An evaluation of ... ...

Abstract	Objective: To evaluate whether frailty or age increases the risk of postoperative complications following cochlear implant (CI) surgery. Study design: Retrospective cohort study. Setting: Tertiary academic center. Methods: An evaluation of all adult patients undergoing cochlear implantation between 2006 and 2020 was performed. The 5-item Modified Frailty Index (mFI-5, comprising preoperative history of pulmonary disease, heart failure, hypertension, diabetes, and partially/totally dependent functional status) was calculated for all patients included in analysis in addition to demographic characteristics. The primary outcome was postoperative complications following CI within a 3-month period. Major complications included myocardial infarction, bleeding, and cerebrospinal fluid leak, among others. Predictors of postoperative complications were examined using multivariable logistic regression reporting odds ratios (ORs) and 95% CIs. Results: There were 520 patients included for review with a median age of 68 (range, 18-94) years and a slight male predominance (n = 283, 54.4%). There were 340 patients (65.4%) who were robust (nonfrail) with an mFI of 0, while 180 (34.6%) had an mFI of ≥1. There were 20 patients who experienced a postoperative complication (3.85%). There was no statistically significant association between postoperative complications as a result of preoperative frailty (OR, 1.56; 95% CI, 0.98-2.48, Conclusions: CI is safe for elderly and frail patients and carries no additional risk of complications when compared to younger, healthier patients. While medical comorbidities should always be considered perioperatively, this study supports the notion that implantation is low risk in older, frail patients.
Language	English
Publishing date	2021-09-24
Publishing country	United States
Document type	Journal Article
ISSN	2473-974X
ISSN (online)	2473-974X
DOI	10.1177/2473974X211044084
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Article ; Online: How good are medical and death records for identifying dementia?

Schliep, Karen C / Ju, Shinyoung / Foster, Norman L / Smith, Ken R / Varner, Michael W / Østbye, Truls / Tschanz, JoAnn T

Alzheimer's & dementia : the journal of the Alzheimer's Association

2021 Volume 18, Issue 10, Page(s) 1812–1823

Abstract: Introduction: Retrospective studies using administrative data may be an efficient way to assess risk factors for dementia if diagnostic accuracy is known.: Methods: Within-individual clinical diagnoses of Alzheimer's disease (AD) and all-cause ... ...

Abstract	Introduction: Retrospective studies using administrative data may be an efficient way to assess risk factors for dementia if diagnostic accuracy is known. Methods: Within-individual clinical diagnoses of Alzheimer's disease (AD) and all-cause dementia in ambulatory (outpatient) surgery, inpatient, Medicare administrative records and death certificates were compared with research diagnoses among participants of Cache County Study on Memory, Health, and Aging (CCSMHA) (1995-2008, N = 5092). Results: Combining all sources of clinical health data increased sensitivity for identifying all-cause dementia (71%) and AD (48%), while maintaining relatively high specificity (81% and 93%, respectively). Medicare claims had the highest sensitivity for case identification (57% and 40%, respectively). Discussion: Administrative health data may provide a less accurate method than a research evaluation for identifying individuals with dementing disease, but accuracy is improved by combining health data sources. Assessing all-cause dementia versus a specific cause of dementia such as AD will result in increased sensitivity, but at a cost to specificity.
MeSH term(s)	Humans ; Aged ; United States ; Dementia/diagnosis ; Retrospective Studies ; Death Certificates ; Medicare ; Alzheimer Disease/diagnosis ; Sensitivity and Specificity
Language	English
Publishing date	2021-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12526
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