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Article: Reduced white matter venous density on MRI is associated with neurodegeneration and cognitive impairment in the elderly.

Li, Chenyang / Rusinek, Henry / Chen, Jingyun / Bokacheva, Louisa / Vedvyas, Alok / Masurkar, Arjun V / Haacke, E Mark / Wisniewski, Thomas / Ge, Yulin

Frontiers in aging neuroscience

2022 Volume 14, Page(s) 972282

Abstract: High-resolution susceptibility weighted imaging (SWI) provides unique contrast to small venous vasculature. The conspicuity of these mesoscopic veins, such as deep medullary veins in white matter, is subject to change from SWI venography when venous ... ...

Abstract	High-resolution susceptibility weighted imaging (SWI) provides unique contrast to small venous vasculature. The conspicuity of these mesoscopic veins, such as deep medullary veins in white matter, is subject to change from SWI venography when venous oxygenation in these veins is altered due to oxygenated blood susceptibility changes. The changes of visualization in small veins shows potential to depict regional changes of oxygen utilization and/or vascular density changes in the aging brain. The goal of this study was to use WM venous density to quantify small vein visibility in WM and investigate its relationship with neurodegenerative features, white matter hyperintensities (WMHs), and cognitive/functional status in elderly subjects (
Language	English
Publishing date	2022-09-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2022.972282
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Article: The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

Jacobs, Tovia / Jacobson, Sean R / Fortea, Juan / Berger, Jeffrey S / Vedvyas, Alok / Marsh, Karyn / He, Tianshe / Gutierrez-Jimenez, Eugenio / Fillmore, Nathanael R / Bubu, Omonigho M / Gonzalez, Moses / Figueredo, Luisa / Gaggi, Naomi L / Plaska, Chelsea Reichert / Pomara, Nunzio / Blessing, Esther / Betensky, Rebecca / Rusinek, Henry / Zetterberg, Henrik /

Blennow, Kaj / Glodzik, Lidia / Wisniewski, Thomas M / Leon, Mony J / Osorio, Ricardo S / Ramos-Cejudo, Jaime

Research square

2024

Abstract: Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into ... ...

Abstract	Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-4076789/v1
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Article ; Online: Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia.

Frontera, Jennifer A / Boutajangout, Allal / Masurkar, Arjun V / Betensky, Rebecca A / Ge, Yulin / Vedvyas, Alok / Debure, Ludovic / Moreira, Andre / Lewis, Ariane / Huang, Joshua / Thawani, Sujata / Balcer, Laura / Galetta, Steven / Wisniewski, Thomas

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

2022 Volume 18, Issue 5, Page(s) 899–910

Abstract: Introduction: Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers.: Methods: Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum ... ...

Abstract	Introduction: Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. Methods: Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). Results: Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. Discussion: Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
MeSH term(s)	Alzheimer Disease ; Amyloid beta-Peptides ; Biomarkers ; COVID-19/complications ; Cognition ; Cognitive Dysfunction ; Hospital Mortality ; Humans ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12556
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Article ; Online: Environmental Noise in New York City Long-Term Care Facilities: A Window Into the COVID-19 Pandemic.

Martin, Jennifer L / Hernandez, Diana / Cadogan, Mary P / Brody, Abraham A / Alessi, Cathy A / Mitchell, Michael N / Song, Yeonsu / Smilowitz, Jessica / Vedvyas, Alok / Qian, Yingzhi / Zhong, Hua / Chodosh, Joshua

Journal of the American Medical Directors Association

2021 Volume 22, Issue 5, Page(s) 974–976

MeSH term(s)	COVID-19 ; Humans ; Long-Term Care ; New York City/epidemiology ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-02-16
Publishing country	United States
Document type	Letter
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2021.02.010
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Article ; Online: Elevation of Neurodegenerative Serum Biomarkers among Hospitalized COVID-19 Patients

Frontera, Jennifer A. / Boutajangout, Allal / Masurkar, Arjun / Betensky, Rebecca A / Ge, Yulin / Vedvyas, Alok / Debure, Ludovic / Moreira, Andre / Lewis, Ariane / Huang, Joshua / Thawani, Sujata / Balcer, Laura / Galetta, Steven / Wisniewski, Thomas

medRxiv

Abstract: INTRODUCTION: Older adults hospitalized with COVID-19 are susceptible to neurological complications, particularly encephalopathy, which may reflect age-related neurodegenerative processes. METHODS: Serum total tau, ptau-181, GFAP, NFL, UCHL1, and amyloid- ...

Abstract	INTRODUCTION: Older adults hospitalized with COVID-19 are susceptible to neurological complications, particularly encephalopathy, which may reflect age-related neurodegenerative processes. METHODS: Serum total tau, ptau-181, GFAP, NFL, UCHL1, and amyloid-beta(AB-40,42) were measured in hospitalized COVID-19 patients without a history of dementia, and compared among patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions using multivariable Cox proportional hazards regression analyses. RESULTS: Among 251 patients, admission serum ptau-181 and UCHL1 were significantly elevated in patients with encephalopathy (both P<0.05) and total tau, GFAP, and NFL were significantly lower in those discharged home(all P<0.05). These markers correlated significantly with severity of COVID illness. NFL, GFAP and UCH-L1 were significantly higher in hospitalized COVID patients than in non-COVID controls with mild cognitive impairment or Alzheimer9s disease(AD). DISCUSSION: Age-related neurodegenerative biomarkers were elevated to levels observed in AD and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
Keywords	covid19
Language	English
Publishing date	2021-09-05
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.09.01.21262985
Database	COVID19

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Article ; Online: Psychometric Cognitive Decline Precedes the Advent of Subjective Cognitive Decline in the Evolution of Alzheimer's Disease.

Reisberg, Barry / Shao, Yongzhao / Moosavi, Mesum / Kenowsky, Sunnie / Vedvyas, Alok / Marsh, Karyn / Bao, Jia / Buj, Maja / Torossian, Carol / Kluger, Alan / Vedvyas, Gaurav / Oo, Thet / Malik, Fawad / Arain, Fauzia / Masurkar, Arjun V / Wisniewski, Thomas

Dementia and geriatric cognitive disorders

2020 Volume 49, Issue 1, Page(s) 16–21

Abstract: Background: We have described the clinical stages of the brain aging and Alzheimer's disease (AD) continuum. In terms of the pre-dementia stages of AD, we introduced the terminology "mild cognitive impairment" (MCI) for the first pre-dementia stage and " ...

Abstract	Background: We have described the clinical stages of the brain aging and Alzheimer's disease (AD) continuum. In terms of the pre-dementia stages of AD, we introduced the terminology "mild cognitive impairment" (MCI) for the first pre-dementia stage and "subjective cognitive decline" (SCD) for the pre-MCI stage. We now report the characteristics of a pre-SCD condition eventuating in likely AD. Objective: The aim of this study was to characterize a pre-SCD condition eventuating in AD. Method: Sixty healthy persons with "no cognitive decline" (NCD) were recruited and 47 were followed (mean baseline age, 64.1 ± 8.9 years; mean follow-up time, 6.7 ± 3.1 years). Outcome was determined at the final assessment prior to 2002 as "decliner," if SCD or worse, or "nondecliner" if NCD. Results: After controlling for age, gender, years of education, and follow-up time, there was a between-group difference in the decline rate (p < 0.001). Also, after controlling for demographic variables and follow-up time, the combinatorial psychometric score was lower at baseline in the future decliners (p = 0.035). Of the 9 psychometric variables, after controlling for demographic variables and follow-up time, 3 were significantly lower at baseline in future decliners. Since AD is known to be age related and all subjects in this study were otherwise healthy, we also did an analysis without controlling for age. The combinatorial psychometric score was highly significantly better at baseline in the future nondecliners than in the future decliners (p = 0.008). Conclusion: This is ostensibly the first study to link psychometric cognitive decline to the subsequent SCD stage of eventual AD.
MeSH term(s)	Aged ; Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Diagnostic Self Evaluation ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Male ; Neuropsychological Tests ; Psychometrics/methods ; Self-Assessment
Language	English
Publishing date	2020-05-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1026007-9
ISSN	1421-9824 ; 1013-7424
ISSN (online)	1421-9824
ISSN	1013-7424
DOI	10.1159/000507286
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Article ; Online: Comprehensive, Individualized, Person-Centered Management of Community-Residing Persons with Moderate-to-Severe Alzheimer Disease: A Randomized Controlled Trial.

Reisberg, Barry / Shao, Yongzhao / Golomb, James / Monteiro, Isabel / Torossian, Carol / Boksay, Istvan / Shulman, Melanie / Heller, Sloane / Zhu, Zhaoyin / Atif, Ayesha / Sidhu, Jaskirat / Vedvyas, Alok / Kenowsky, Sunnie

Dementia and geriatric cognitive disorders

2017 Volume 43, Issue 1-2, Page(s) 100–117

Abstract: Background/aims: The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment.: Methods: This was a 28-week, clinician-blinded, randomized, controlled, parallel-group ... ...

Abstract	Background/aims: The aim was to examine added benefits of a Comprehensive, Individualized, Person-Centered Management (CI-PCM) program to memantine treatment. Methods: This was a 28-week, clinician-blinded, randomized, controlled, parallel-group study, with a similar study population, similar eligibility criteria, and a similar design to the memantine pivotal trial of Reisberg et al. [N Engl J Med 2003;348:1333-1341]. Twenty eligible community-residing Alzheimer disease (AD) subject-caregiver dyads were randomized to the CI-PCM program (n = 10) or to usual community care (n = 10). Primary outcomes were the New York University Clinician's Interview-Based Impression of Change Plus Caregiver Input (NYU-CIBIC-Plus), assessed by one clinician set, and an activities of daily living inventory, assessed by a separate clinician set at baseline and at weeks 4, 12, and 28. Results: Primary outcomes showed significant benefits of the CI-PCM program at all post-baseline evaluations. Improvement on the NYU-CIBIC-Plus in the management group at 28 weeks was 2.9 points over the comparator group. The memantine 2003 trial showed an improvement of 0.3 points on this global measure in memantine-treated versus placebo-randomized subjects at 28 weeks. Hence, globally, the management program intervention benefits were 967% greater than memantine treatment alone. Conclusion: These results are approximately 10 times those usually observed with both nonpharmacological and pharmacological treatments and indicate substantial benefits with the management program for advanced AD persons.
MeSH term(s)	Activities of Daily Living ; Aged ; Aged, 80 and over ; Alzheimer Disease/drug therapy ; Alzheimer Disease/therapy ; Caregivers ; Case Management ; Double-Blind Method ; Female ; Humans ; Male ; Memantine/therapeutic use ; Middle Aged ; Nootropic Agents/therapeutic use ; Precision Medicine/methods ; Treatment Outcome
Chemical Substances	Nootropic Agents ; Memantine (W8O17SJF3T)
Language	English
Publishing date	2017-01-26
Publishing country	Switzerland
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1026007-9
ISSN	1421-9824 ; 1013-7424
ISSN (online)	1421-9824
ISSN	1013-7424
DOI	10.1159/000455397
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Article ; Online: Two Year Outcomes, Cognitive and Behavioral Markers of Decline in Healthy, Cognitively Normal Older Persons with Global Deterioration Scale Stage 2 (Subjective Cognitive Decline with Impairment).

Reisberg, Barry / Torossian, Carol / Shulman, Melanie B / Monteiro, Isabel / Boksay, Istvan / Golomb, James / Guillo Benarous, Francoise / Ulysse, Anaztasia / Oo, Thet / Vedvyas, Alok / Rao, Julia A / Marsh, Karyn / Kluger, Alan / Sangha, Jaspreet / Hassan, Mudasar / Alshalabi, Munther / Arain, Fauzia / Shaikh, Naveed / Buj, Maja /

Kenowsky, Sunnie / Masurkar, Arjun V / Rabin, Laura / Noroozian, Maryam / Sánchez-Saudinós, Mar A Belén / Blesa, Rafael / Auer, Stefanie / Zhang, Yian / de Leon, Mony / Sadowski, Martin / Wisniewski, Thomas / Gauthier, Serge / Shao, Yongzhao

Journal of Alzheimer's disease : JAD

2019 Volume 67, Issue 2, Page(s) 685–705

Abstract: Background: Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2.: Objective: Two-year interval behavioral markers were ... ...

Abstract	Background: Little is known with respect to behavioral markers of subjective cognitive decline (SCD), a condition initially described in association with Global Deterioration Scale (GDS) stage 2. Objective: Two-year interval behavioral markers were investigated herein. Methods: Subjects from a published 7-year outcome study of GDS stage 2 subjects were selected. This study had demonstrated a hazard ratio of 4.5 for progression of GDS stage 2, in comparison with GDS stage 1 (no subjective or objective cognitive decline) subjects, after controlling for demographic and temporal variables. Because GDS 2 subjects have previously demonstrated impairment in comparison with healthy persons free of complaints, we herein suggest the terminology "SCD(I)" for these persons. 98 SCD(I) persons, 63 women and 35 men, mean baseline age, 67.12±8.75 years, with a mean educational background of 15.55±2.60 years, and mean baseline MMSE scores of 28.9±1.24 were followed for 2.13±0.30 years. Results: Observed annual decline on the GDS was 6.701% per annum, very close to a 1986 published estimate. At follow up, the MMSE, and 7 of 8 psychometric tests did not decline significantly. Of 21 Hamilton Depression Scale items, 2 improved and the remainder were unchanged. Anxieties declined from multiple perspectives. The Brief Cognitive Rating Scale (BCRS) declined significantly (p < 0.001), with component declines in Remote memory (p < 0.01), and Functioning/self-care (p = 0.01). Conclusion: SCD(I) persons decline at an annual rate of approximately 6.7% /year from several recent studies. The BCRS assessments and the Digit Symbol Substitution Test can be sensitive measures for future studies of progression mitigation.
MeSH term(s)	Affect ; Aged ; Anxiety/complications ; Anxiety/psychology ; Behavior ; Biomarkers ; Cognition Disorders/psychology ; Cognitive Dysfunction/psychology ; Depression/complications ; Depression/psychology ; Disease Progression ; Female ; Humans ; Longitudinal Studies ; Male ; Mental Status and Dementia Tests ; Middle Aged ; Neuropsychological Tests ; Psychometrics ; Self Care ; Treatment Outcome
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-01-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-180341
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Article ; Online: The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer's disease.

Reisberg, Barry / Prichep, Leslie / Mosconi, Lisa / John, E Roy / Glodzik-Sobanska, Lidia / Boksay, Istvan / Monteiro, Isabel / Torossian, Carol / Vedvyas, Alok / Ashraf, Nauman / Jamil, Imran A / de Leon, Mony J

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

2007 Volume 4, Issue 1 Suppl 1, Page(s) S98–S108

Abstract: Background: Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons.: Methods: The past and the emerging literature on SCI and synonymously named conditions is reviewed.: ... ...

Abstract	Background: Subjective cognitive impairment (SCI) has been a common, but poorly understood condition, frequently occurring in older persons. Methods: The past and the emerging literature on SCI and synonymously named conditions is reviewed. Results: Findings include: (1) There is support from at least one longitudinal study for a long-standing concept of SCI as a pre-mild cognitive impairment (MCI) condition lasting approximately 15years. (2) There are complex relationships between SCI and depression and anxiety. (3) Differences in SCI subjects from age-matched non-SCI persons are being published in terms of cognitive tests, hippocampal gray matter density, hippocampal volumes, cerebral metabolism, and urinary cortisol levels. Psychometric and dementia test score differences between SCI and MCI subjects have long been evident. (4) Predictive electrophysiologic features of subsequent decline in SCI subjects are being published. Conclusions: Studies of therapeutic agents in SCI treatment and resultant Alzheimer's disease prevention appear to be feasible. These trials are also necessary from a public health perspective.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Brain/pathology ; Cognition Disorders/diagnosis ; Cognition Disorders/etiology ; Cognition Disorders/pathology ; Disease Progression ; Humans ; Neuropsychological Tests
Language	English
Publishing date	2007-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1016/j.jalz.2007.11.017
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