Two Distinct Classes of Degenerative Change Are Independently Linked to Clinical Progression in Mild Cognitive Impairment

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2017 Mar 14

PMID 28286328

Citations 14

Authors

Jean-Philippe Coutu

Emily R Lindemer

Ender Konukoglu

David H Salat

Affiliations

Soon will be listed here.

Abstract

We previously demonstrated 2 statistically distinct factors of degeneration in Alzheimer's disease: one strongly related to white matter damage and age interpreted as "age- and vascular-related", and the other related to cortical atrophy thought to represent "neurodegenerative changes associated with Alzheimer's disease". Those factors are now replicated in a distinct cross-sectional data set of 364 participants from the Alzheimer's Disease Neuroimaging Initiative and their interpretation is improved using correlations with CSF biomarkers. Furthermore, we now show that changes in both factors over 2 years are independently associated with decline in Mini-Mental State Examination score in a longitudinal subset of 116 individuals with mild cognitive impairment. Progression in the "age- and vascular-related" factor was greater for individuals with 2 APOE ε4 alleles and linked to a greater attributable change in Mini-Mental State Examination than the "neurodegenerative" factor. These results suggest benefits of targeting white matter and vascular health to complement interventions focused on the neurodegenerative aspect of the disease, even in individuals with little discernable vascular comorbidity.

Citing Articles

Impact of white matter hyperintensities on structural connectivity and cognition in cognitively intact ADNI participants.

Taghvaei M, Mechanic-Hamilton D, Sadaghiani S, Shakibajahromi B, Dolui S, Das S Neurobiol Aging. 2024; 135:79-90.

PMID: 38262221 PMC: 10872454. DOI: 10.1016/j.neurobiolaging.2023.10.012.

Koenig L, LaMontagne P, Glasser M, Bateman R, Holtzman D, Yakushev I Neurobiol Aging. 2021; 109:43-51.

PMID: 34655980 PMC: 9009406. DOI: 10.1016/j.neurobiolaging.2021.09.010.

Cerebroprotein hydrolysate-I protects senescence-induced by D-galactose in PC12 cells and mice.

Zhu L, Liu Y, Wu X, Ren Y, Zhang Q, Ren L Food Sci Nutr. 2021; 9(7):3722-3731.

PMID: 34262731 PMC: 8269606. DOI: 10.1002/fsn3.2333.

Heterogeneity of Cerebral White Matter Lesions and Clinical Correlates in Older Adults.

Jung K, Stephens K, Yochim K, Riphagen J, Kim C, Buckner R Stroke. 2021; 52(2):620-630.

PMID: 33406867 PMC: 9477514. DOI: 10.1161/STROKEAHA.120.031641.

Prediction of clinical and biomarker conformed Alzheimer's disease and mild cognitive impairment from multi-feature brain structural MRI using age-correction from a large independent lifespan sample.

Li B, Zhang M, Riphagen J, Yochim K, Li B, Liu J Neuroimage Clin. 2020; 28:102387.

PMID: 32871388 PMC: 7476071. DOI: 10.1016/j.nicl.2020.102387.

References

Haan M, Shemanski L, Jagust W, Manolio T, Kuller L . The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA. 1999; 282(1):40-6. DOI: 10.1001/jama.282.1.40. View

Laakso M, Partanen K, RIEKKINEN P, Lehtovirta M, Helkala E, Hallikainen M . Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: An MRI study. Neurology. 1996; 46(3):678-81. DOI: 10.1212/wnl.46.3.678. View

Wolf P, DAgostino R, Belanger A, Kannel W . Probability of stroke: a risk profile from the Framingham Study. Stroke. 1991; 22(3):312-8. DOI: 10.1161/01.str.22.3.312. View

Pantoni L . Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010; 9(7):689-701. DOI: 10.1016/S1474-4422(10)70104-6. View

Gouw A, Seewann A, van der Flier W, Barkhof F, Rozemuller A, Scheltens P . Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry. 2010; 82(2):126-35. DOI: 10.1136/jnnp.2009.204685. View

Vemuri P, Lesnick T, Przybelski S, Knopman D, Preboske G, Kantarci K . Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly. Brain. 2015; 138(Pt 3):761-71. PMC: 4339775. DOI: 10.1093/brain/awu393. View

Kim J, Han S, Chung S, Kim B, Lee K, Kim Y . The apolipoprotein E epsilon4 haplotype is an important predictor for recurrence in ischemic cerebrovascular disease. J Neurol Sci. 2002; 206(1):31-7. DOI: 10.1016/s0022-510x(02)00361-1. View

Gouw A, van der Flier W, Fazekas F, van Straaten E, Pantoni L, Poggesi A . Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the Leukoaraiosis and Disability study. Stroke. 2008; 39(5):1414-20. DOI: 10.1161/STROKEAHA.107.498535. View

Jeerakathil T, Wolf P, Beiser A, Massaro J, Seshadri S, DAgostino R . Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study. Stroke. 2004; 35(8):1857-61. DOI: 10.1161/01.STR.0000135226.53499.85. View

10.

Richard E, Gouw A, Scheltens P, van Gool W . Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study. Stroke. 2010; 41(3):554-6. DOI: 10.1161/STROKEAHA.109.571281. View

11.

Fischl B, Salat D, Busa E, Albert M, Dieterich M, Haselgrove C . Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002; 33(3):341-55. DOI: 10.1016/s0896-6273(02)00569-x. View

12.

Jellinger K, Attems J . Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 2010; 119(4):421-33. DOI: 10.1007/s00401-010-0654-5. View

13.

Iadecola C . The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol. 2010; 120(3):287-96. PMC: 3001188. DOI: 10.1007/s00401-010-0718-6. View

14.

Burton E, McKeith I, Burn D, Firbank M, OBrien J . Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging. Am J Geriatr Psychiatry. 2006; 14(10):842-9. DOI: 10.1097/01.JGP.0000236596.56982.1c. View

15.

Gottesman R, Coresh J, Catellier D, Sharrett A, Rose K, Coker L . Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2009; 41(1):3-8. PMC: 2803313. DOI: 10.1161/STROKEAHA.109.566992. View

16.

ROSEN W, Terry R, Fuld P, Katzman R, Peck A . Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980; 7(5):486-8. DOI: 10.1002/ana.410070516. View

17.

Bakkour A, Morris J, Dickerson B . The cortical signature of prodromal AD: regional thinning predicts mild AD dementia. Neurology. 2008; 72(12):1048-55. PMC: 2677470. DOI: 10.1212/01.wnl.0000340981.97664.2f. View

18.

Mohs R, Knopman D, Petersen R, Ferris S, Ernesto C, Grundman M . Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2:S13-21. View

19.

Jack Jr C, Knopman D, Jagust W, Shaw L, Aisen P, Weiner M . Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010; 9(1):119-28. PMC: 2819840. DOI: 10.1016/S1474-4422(09)70299-6. View

20.

Morris J . The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993; 43(11):2412-4. DOI: 10.1212/wnl.43.11.2412-a. View