Evidence map›Paper›PMID 29377010›Full record

ReviewNature reviews. Neurology2018

Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums.

Steven E Arnold, Zoe Arvanitakis, Shannon L Macauley-Rambach, Aaron M Koenig, Hoau-Yan Wang, Rexford S Ahima, Suzanne Craft, Sam Gandy, Christoph Buettner, Luke E Stoeckel and 2 more

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nature reviews. Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07177781 (Longer-term Effects of Wild Blueberry Consumption on Brain Function in Older Men and Women), which is not on this map. Cited by 825 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
825citing papers in PubMed, 8 pooled it
82.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07177781 narecruitingnot on this mapstarted 2024, after this paper: background citation

Longer-term Effects of Wild Blueberry Consumption on Brain Function in Older Men and Women

TypeinterventionalSponsorMaastricht University Medical CenterRan2024 to 2026Enrolled36ConditionsBrain Insulin-sensitivity, Brain Vascular Function, Cerebral Blood FlowArmsWild blueberry powder
3 · Its place in the literature

Who cites it

825 citing papers in PubMed, 8 syntheses or guidelines pooled it, 1,461 citations in OpenAlex.

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  11. Sleep apnea in REM sleep as an amplifier of vascular contributions to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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765 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 9 institutions in 1 country.

Steven E ArnoldDepartment of Neurology and the Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
Zoe ArvanitakisRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 1750 W. Harrison Street, Suite 1000, Chicago, Illinois 60612, USA.
Shannon L Macauley-RambachHope Center for Neurological Disorders, Department of Neurology, Campus Box 8111, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.
Aaron M KoenigDepartment of Neurology and the Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
Hoau-Yan WangDepartment of Physiology, Pharmacology and Neuroscience, City University of New York School of Medicine, 160 Convent Avenue, New York, New York 10031, USA.
Rexford S AhimaDivision of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, 333 East Monument Street, Baltimore, Maryland 21205, USA.
Suzanne CraftGerontology and Geriatric Medicine Center on Diabetes, Obesity, and Metabolism, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA.
Sam GandyDepartments of Neurology and Psychiatry and the Mount Sinai Alzheimer's Disease Research Center, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1230, New York, New York 10029, USA.
Christoph BuettnerDiabetes, Obesity, and Metabolism Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Luke E StoeckelNational Institute of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Boulevard, Bethesda, Maryland 20817, USA. Diabetes Center and Clinical Research Center, Massachusetts General Hospital, Harvard Medical School, Bullfinch 55 Fruit Street, Boston, Massachusetts 02114, USA.
David M HoltzmanHope Center for Neurological Disorders, Department of Neurology, Campus Box 8111, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63110, USA.
David M NathanNational Institute of Diabetes and Digestive and Kidney Diseases, 6707 Democracy Boulevard, Bethesda, Maryland 20817, USA. Diabetes Center and Clinical Research Center, Massachusetts General Hospital, Harvard Medical School, Bullfinch 55 Fruit Street, Boston, Massachusetts 02114, USA.
Hope Center for Neurological Disorders · USIcahn School of Medicine at Mount Sinai · USNational Institute of Diabetes and Digestive and Kidney Diseases · USAtrium Health Wake Forest Baptist · USHarvard University · USJohns Hopkins Medicine · USMassachusetts General Hospital · USNew York University · USRush University Medical Center · US

Funding

Mechanisms linking insulin resistance to brain structure, pathology, and functionR01NS084965 · NINDS · RUSH UNIVERSITY MEDICAL CENTER · PI AHIMA, REXFORD S., ARNOLD, STEVEN E · 2014 to 2018
$3.2M
Assessment of Brain Insulin Resistance in Alzheimer's Disease with Insulin ClampR21AG051958 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI ARNOLD, STEVEN E · 2016 to 2017
$470k
NIA NIH HHS R21 AG051958NINDS NIH HHS R01 NS084965
6 · The paper itself

Abstract

Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.

Indexed as

Insulin ResistanceBrainDementiaDiabetes Mellitus, Type 2HumansInsulinInsulin

Identifiers

PMID29377010
PMCPMC6098968
OpenAlexW2786962139

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.