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  1. Article ; Online: Presymptomatic Profiles of Cognitive Impairment with Prior Mobility Impairment.

    Tian, Qu / An, Yang / Resnick, Susan M / Ferrucci, Luigi

    Journal of the American Medical Directors Association

    2024  Volume 25, Issue 3, Page(s) 480–487.e2

    Abstract: Objectives: To identify cognitive and health profiles of cognitively impaired older adults with the presence of prior mobility impairment, which may represent a specific pathway to the development of cognitive impairment or dementia.: Design: ... ...

    Abstract Objectives: To identify cognitive and health profiles of cognitively impaired older adults with the presence of prior mobility impairment, which may represent a specific pathway to the development of cognitive impairment or dementia.
    Design: Retrospective longitudinal study.
    Setting and participants: In adults aged ≥65 years who developed cognitive impairment or dementia, we compared cognitive and health profiles of those who did (n = 57) and did not (n = 86) experience slow gait up to 14 years before symptom onset. Measures of cognitive and biomarkers assessed longitudinally over an average of 7 years before symptom onset were compared between groups using linear mixed effects models, adjusted age, sex, race, and additionally adjusted for education for cognitive outcomes.
    Results: Compared to those without prior slow gait, those with slow gait had lower Digit Symbol Substitution Test and Pegboard dominant and nondominant hand performance. The slow gait group also had greater body mass index (BMI), waist, systolic blood pressure, lower high-density lipoprotein and low-density lipoprotein, and lower lysophosphatidylcholine 18:2, a lipid associated with mitochondrial function, and showed greater increases in 2-hour glucose levels of an oral glucose tolerance test. The slow gait group was more likely to take medication for hypertension and hypercholesterolemia.
    Conclusions and implications: During the presymptomatic stage, cognitively impaired older persons who experience prior slow gait are more likely to have deficits in psychomotor speed and manual dexterity, an unfavorable metabolic and vascular profile, and lower lipid levels related to mitochondrial function. Older persons who exhibit mobility impairment should be evaluated for metabolic and vascular dysfunction at an early stage, and successful treatment of these conditions may slow down the progression of cognitive impairment or dementia.
    MeSH term(s) Humans ; Aged ; Aged, 80 and over ; Longitudinal Studies ; Retrospective Studies ; Cognitive Dysfunction ; Dementia ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2171030-2
    ISSN 1538-9375 ; 1525-8610
    ISSN (online) 1538-9375
    ISSN 1525-8610
    DOI 10.1016/j.jamda.2023.12.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Amyloid Positivity as a Risk Factor for Memory Decline and Lower Memory Performance as an Indicator of Conversion to Amyloid Positivity: Chicken and Egg.

    Bilgel, Murat / Resnick, Susan M

    Biological psychiatry

    2020  Volume 87, Issue 9, Page(s) 782–784

    MeSH term(s) Amyloid ; Cognition ; Cognitive Dysfunction ; Humans ; Memory Disorders ; Risk Factors
    Chemical Substances Amyloid
    Language English
    Publishing date 2020-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Comment
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2020.02.006
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  3. Article ; Online: Associations of olfactory function with brain structural and functional outcomes. A systematic review.

    Bothwell, Adam R / Resnick, Susan M / Ferrucci, Luigi / Tian, Qu

    Ageing research reviews

    2023  Volume 92, Page(s) 102095

    Abstract: In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of neurodegenerative disease. A comprehensive review of the neural correlates of olfactive function may ... ...

    Abstract In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of neurodegenerative disease. A comprehensive review of the neural correlates of olfactive function may reveal mechanisms underlying the associations among olfaction, cognition, motor function, and neurodegenerative diseases. Here, we summarize existing knowledge on the relationship between brain structural and functional measures and olfaction in older adults without and with cognitive impairment, including Alzheimer's disease. We identified 33 eligible studies (30 MRI/DTI,3 fMRI); 31 were cross-sectional, most assessed odor identification, and few examined multiple brain areas. Lower olfactory function was associated with smaller volumes in the temporal lobe (hippocampus,parahippocampal gyrus,fusiform gyrus), olfactory-related regions (piriform cortex,amygdala,entorhinal cortex), pre- and postcentral gyri, and globus pallidus. During aging, olfactory impairment may be associated with pathology in brain areas important for motor function and cognition, especially memory. Future longitudinal studies that include neuroimaging across different brain areas are warranted to determine the neurobiological changes underlying olfactory changes in the aging brain and the progression of neurodegeneration.
    MeSH term(s) Humans ; Aged ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/pathology ; Brain/pathology ; Entorhinal Cortex/pathology ; Hippocampus/pathology ; Temporal Lobe ; Magnetic Resonance Imaging/methods ; Cognitive Dysfunction/pathology
    Language English
    Publishing date 2023-10-30
    Publishing country England
    Document type Systematic Review ; Journal Article ; Review
    ZDB-ID 2075672-0
    ISSN 1872-9649 ; 1568-1637
    ISSN (online) 1872-9649
    ISSN 1568-1637
    DOI 10.1016/j.arr.2023.102095
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  4. Article ; Online: Causal links among amyloid, tau, and neurodegeneration.

    Bilgel, Murat / Wong, Dean F / Moghekar, Abhay R / Ferrucci, Luigi / Resnick, Susan M

    Brain communications

    2022  Volume 4, Issue 4, Page(s) fcac193

    Abstract: Amyloid- ...

    Abstract Amyloid-
    Language English
    Publishing date 2022-07-25
    Publishing country England
    Document type Journal Article
    ISSN 2632-1297
    ISSN (online) 2632-1297
    DOI 10.1093/braincomms/fcac193
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  5. Article ; Online: Plasma metabolomic markers underlying skeletal muscle mitochondrial function relationships with cognition and motor function.

    Tian, Qu / Greig, Erin E / Walker, Keenan A / Fishbein, Kenneth W / Spencer, Richard G / Resnick, Susan M / Ferrucci, Luigi

    Age and ageing

    2024  Volume 53, Issue 4

    Abstract: Background: Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle ...

    Abstract Background: Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function.
    Methods: We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4 years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black).
    Results: The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures.
    Conclusion: Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes.
    MeSH term(s) Female ; Humans ; Aged ; Male ; Longitudinal Studies ; Lysophosphatidylcholines ; Muscle, Skeletal ; Cognition ; Cognitive Dysfunction
    Chemical Substances Lysophosphatidylcholines
    Language English
    Publishing date 2024-03-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 186788-x
    ISSN 1468-2834 ; 0002-0729
    ISSN (online) 1468-2834
    ISSN 0002-0729
    DOI 10.1093/ageing/afae079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Speaking the Same Language: Team Science Approaches in Aging Research for Integrating Basic and Translational Science With Clinical Practice.

    Sukoff Rizzo, Stacey J / Finkel, Toren / Greenspan, Susan L / Resnick, Neil M / Brach, Jennifer S

    Innovation in aging

    2023  Volume 7, Issue 4, Page(s) igad035

    Abstract: Research on aging is at an important inflection point, where the insights accumulated over the last 2 decades in the basic biology of aging are poised to be translated into new interventions to promote health span and improve longevity. Progress in the ... ...

    Abstract Research on aging is at an important inflection point, where the insights accumulated over the last 2 decades in the basic biology of aging are poised to be translated into new interventions to promote health span and improve longevity. Progress in the basic science of aging is increasingly influencing medical practice, and the application and translation of geroscience require seamless integration of basic, translational, and clinical researchers. This includes the identification of new biomarkers, novel molecular targets as potential therapeutic agents, and translational in vivo studies to assess the potential efficacy of new interventions. To facilitate the required dialog between basic, translational, and clinical investigators, a multidisciplinary approach is essential and requires the collaborative expertise of investigators spanning molecular and cellular biology, neuroscience, physiology, animal models, physiologic and metabolic processes, pharmacology, genetics, and high-throughput drug screening approaches. In an effort to better enable the cross-talk of investigators across the broad spectrum of aging-related research disciplines, a goal of our University of Pittsburgh Claude D. Pepper Older Americans Independence Center has been to reduce the barriers to collaborative interactions by promoting a common language through team science. The culmination of these efforts will ultimately accelerate the ability to conduct first-in-human clinical trials of novel agents to extend health span and life span.
    Language English
    Publishing date 2023-04-26
    Publishing country England
    Document type Journal Article
    ISSN 2399-5300
    ISSN (online) 2399-5300
    DOI 10.1093/geroni/igad035
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  7. Article ; Online: Skin Barrier Function and Cognition among Older Adults.

    Kim, Richard W / An, Yang / Zukley, Linda / Ferrucci, Luigi / Mauro, Theodora / Yaffe, Kristine / Resnick, Susan M / Abuabara, Katrina

    The Journal of investigative dermatology

    2023  Volume 143, Issue 6, Page(s) 1085–1087

    MeSH term(s) Cognition ; Humans ; Aged ; Skin Physiological Phenomena
    Language English
    Publishing date 2023-01-11
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2022.11.023
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  8. Article ; Online: Preclinical biomarkers in Alzheimer disease: a sum greater than the parts.

    Resnick, Susan M

    JAMA neurology

    2014  Volume 71, Issue 11, Page(s) 1357–1358

    MeSH term(s) Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/metabolism ; Cognition/physiology ; Cognition Disorders/diagnosis ; Female ; Humans ; Male
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2014-09-15
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2702023-X
    ISSN 2168-6157 ; 2168-6149
    ISSN (online) 2168-6157
    ISSN 2168-6149
    DOI 10.1001/jamaneurol.2014.2462
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  9. Article ; Online: Lower myelin content is associated with more rapid cognitive decline among cognitively unimpaired individuals.

    Gong, Zhaoyuan / Bilgel, Murat / Kiely, Matthew / Triebswetter, Curtis / Ferrucci, Luigi / Resnick, Susan M / Spencer, Richard G / Bouhrara, Mustapha

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

    2023  Volume 19, Issue 7, Page(s) 3098–3107

    Abstract: Introduction: The influence of myelination on longitudinal changes in cognitive performance remains unclear.: Methods: For each participant (N = 123), longitudinal cognitive scores were calculated. Myelin content was probed using myelin water ... ...

    Abstract Introduction: The influence of myelination on longitudinal changes in cognitive performance remains unclear.
    Methods: For each participant (N = 123), longitudinal cognitive scores were calculated. Myelin content was probed using myelin water fraction (MWF) or longitudinal relaxation rate (R
    Results: Lower MWF was associated with steeper declines in executive function (p < .02 in all regions) and lower R
    Discussion: We demonstrate significant relationships between myelin content and the rates of change in cognitive performance among cognitively normal individuals. These findings highlight the importance of myelin in cognitive functioning and suggest MWF and R
    MeSH term(s) Humans ; Myelin Sheath ; Cognition ; Executive Function ; White Matter/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Cognitive Dysfunction/diagnostic imaging ; Brain
    Language English
    Publishing date 2023-01-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.12968
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Walking energetics and white matter hyperintensities in mid-to-late adulthood.

    Dougherty, Ryan J / Wanigatunga, Amal A / An, Yang / Tian, Qu / Simonsick, Eleanor M / Albert, Marilyn S / Resnick, Susan M / Schrack, Jennifer A

    Alzheimer's & dementia (Amsterdam, Netherlands)

    2023  Volume 15, Issue 4, Page(s) e12501

    Abstract: Introduction: White matter hyperintensities (WMHs) increase with age and contribute to cognitive and motor function decline. Energy costs for mobility worsen with age, as the energetic cost of walking increases and energetic capacity declines. We ... ...

    Abstract Introduction: White matter hyperintensities (WMHs) increase with age and contribute to cognitive and motor function decline. Energy costs for mobility worsen with age, as the energetic cost of walking increases and energetic capacity declines. We examined the cross-sectional associations of multiple measures of walking energetics with WMHs in mid- to late-aged adults.
    Methods: A total of 601 cognitively unimpaired adults (mean age 66.9 ± 15.3 years, 54% women) underwent brain magnetic resonance imaging scans and completed standardized slow- and peak-paced walking assessments with metabolic measurement (V̇O
    Results: Lower slow-paced V̇O
    Discussion: The cost-to-capacity ratio, which describes the percentage of capacity required for ambulation, was the walking energetic measure most strongly associated with WMHs.
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2832898-X
    ISSN 2352-8729
    ISSN 2352-8729
    DOI 10.1002/dad2.12501
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