White matter hyperintensities are associated with subthreshold amyloid accumulation
Open accessAbstract
The association between white matter hyperintensities (WMH) and amyloid accumulation over time in cognitively normal, amyloid-negative elderly people remains largely unexplored. In order to study whether baseline WMH were associated with longitudinal subthreshold amyloid accumulation, 159 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative who were amyloid-negative at baseline were examined. All the participants underwent a T1 and a Fluid-Attenuated Inversion Recovery MRI scan at baseline. Amyloid PET imaging was performed at baseline and follow-up visits in 2-year intervals for up to 8 years. Partial volume correction was applied for quantifying cortical Standardised Uptake Value Ratios (SUVR). The associations between global and regional WMH burden and amyloid accumulation were assessed using linear mixed models adjusted by demographic characteristics and baseline SUVR. Partial volume correction increased the measured annual rate of change (+2.4%) compared to that obtained from non-corrected data (+0.5%). There were no significant correlations between baseline WMHs and baseline subthreshold cortical amyloid uptake. In a longitudinal analysis, increased baseline cortical SUVR and increased baseline burden of global (p = 0.006), frontal (p = 0.006), and parietal WMH (p = 0.003) were associated with faster amyloid accumulation. WMH-related amyloid accumulation occurred in parietal, frontal, and, to a lesser extent, cingulate cortices. These results remained unchanged after a sensitivity analysis excluding participants with the highest cortical SUVRs. This is the first study to identify a specific spatial distribution of WMH which is associated with future amyloid accumulation in cognitively normal elderly subjects without PET-detectable amyloid pathology. These findings may have important implications in prevention trials for the early identification of amyloid accumulation.
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WMHs often occur prior to the presence of amyloid-β plaques in preclinical AD.
“findings from previous studies have also shown that WMHs often occur prior to the presence of amyloid-β plaques in preclinical AD [19,20,21]”
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“…by the ADNI PET core for longitudinal Amyloid PET imaging (https://adni.bitbucket.io/reference/docs/UCBERKELEYAV45/ADNI_A V45_Methods_JagustLab_06.25.15.pdf), recent studies have shown that tracer uptake in WMH is lower than in normal-appearing WM (Zeydan et al., 2019; Glodzik et al., 2015).”
InfluentialSkoog, I. G., Kern, S., Zetterberg, H., Östling, S., Börjesson‐Hanson, A., Guo, X., & Blennow, K. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170950 · Cited by 17 · see citing works
Initiative, A. D. N., López‐González, F. J., Moscoso, A., Efthimiou, N., Fernández‐Ferreiro, A., Piñeiro-Fiel, M., Archibald, S. J., Aguiar, P., & Silva‐Rodríguez, J. (2019) · EJNMMI Physics · doi:10.1186/s40658-019-0258-7 · Cited by 17 · see citing works
McMillan, C. T., & Chételat, G. (2018) · Neurology · doi:10.1212/wnl.0000000000005362 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Moscoso, A., Grothe, M. J., Ashton, N. J., Karikari, T. K., Lantero‐Rodriguez, J., Snellman, A., Suárez‐Calvet, M., Blennow, K., Zetterberg, H., Schöll, M., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4986 · Cited by 310 · see citing works
Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum
Moscoso, A., Grothe, M. J., Ashton, N. J., Karikari, T. K., Rodriguez, J. L., Snellman, A., Suárez-Calvet, M., Zetterberg, H., Blennow, K., Schöll, M., et al. (2021) · Brain · doi:10.1093/brain/awaa399 · Cited by 229 · see citing works
“Our findings can thus not easily be extrapolated to the population at large, and possible effects of vascular pathology (Graff-Radford et al., 2019; Caballero et al., 2020; Moscoso et al., 2020) and other common comorbidities on amyloid-b and plasma p-tau181 levels remain to be studied in less selected cohorts.”
Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., DeCarli, C., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Landau, S. M., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12422 · Cited by 184 · see citing works
Cerebral Small Vessel Disease and Alzheimer's Disease: A Review
Kim, H. W., Hong, J., & Jeon, J. C. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00927 · Cited by 108 · see citing works
Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions
Mok, V., Cai, Y., & Markus, H. S. (2024) · International Journal of Stroke · doi:10.1177/17474930241279888 · Cited by 107 · see citing works
“Other MRI lesions similar to that of sporadic SVD (e.g. WMH, CMB, and enlarged PVS) are also common in CAA, 48 and these can induce cognitive impairment even in the absence of stroke, with a recent study reporting that altered white matter diffusivity on DTI, cerebral atrophy, and altered cerebrovascular reactivity ac…”
BackgroundInfluentialMcAleese, K. E., Miah, M., Graham, S., Hadfield, G. M., Walker, L., Johnson, M. A., Colloby, S. J., Thomas, A. J., DeCarli, C. S., Koss, D. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02376-2 · Cited by 95 · see citing works
Gaubert, M., Lange, C., Garnier‐Crussard, A., Köbe, T., Bougacha, S., Gonneaud, J., de Florès, R., Tomadesso, C., Mézenge, F., Landeau, B., et al. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00759-3 · Cited by 62 · see citing works
“Other imaging studies with cognitively normal or non-demented older participants have shown associations between regional WMH (frontal and parietal) and elevated Aβ deposition at baseline and over time [11, 38].”
BackgroundWhite matter hyperintensity distribution differences in aging and neurodegenerative disease cohorts
Dadar, M., Mahmoud, S., Zhernovaia, M., Camicioli, R. M., Maranzano, J., Duchesne, S., & For the CCNA Group (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2022.103204 · Cited by 59 · see citing works
“With regards to links to the underlying proteinopathy, several studies have shown associations between Aβ burden and WMH volume both cross-sectionally and longitudinally in aging, MCI, and AD populations (Graff-Radford et al., 2019; Grimmer et al., 2012; Moscoso et al., 2020; Dadar et al., 2020a; Gurol et al., 2006) a…”
Moscoso, A., Karikari, T. K., Grothe, M. J., Ashton, N. J., Lantero‐Rodriguez, J., Snellman, A., Zetterberg, H., Blennow, K., & Schöll, M. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12570 · Cited by 50 · see citing works
PET imaging of neural activity, β-amyloid, and tau in normal brain aging
Zhang, K., Mizuma, H., Zhang, X., Takahashi, K., Jin, C., Song, F., Gao, Y., Kanayama, Y., Wu, Y., Li, Y., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05230-5 · Cited by 50 · see citing works
Mirkin, S., & Albensi, B. C. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1094233 · Cited by 46 · see citing works
“Although the relation between white matter lesions and amyloid accumulation is unclear, a study suggests WMH may potentially help identify early amyloid accumulation in patients (Moscoso et al., 2020).”
BackgroundVascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET
Ottoy, J., Ozzoude, M., Zukotynski, K., Adamo, S. M., Scott, C. J. M., Gaudet, V., Ramirez, J., Swardfager, W., Cogo‐Moreira, H., Lam, B., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12750 · Cited by 46 · see citing works
Spatial patterns of white matter hyperintensities: a systematic review
Botz, J., Lohner, V., & Schirmer, M. D. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1165324 · Cited by 40 · see citing works
“Thirteen studies utilized a voxel-wise analysis approach (Holland et al., 2008; Dalaker et al., 2009; Jefferson et al., 2011; Smith et al., 2011; Rostrup et al., 2012; Quattrocchi et al., 2014; Torso et al., 2015; Al-Janabi et al., 2018; Altermatt et al., 2019; Damulina et al., 2019; Graff-Radford et al., 2019; Moscos…”
InfluentialBiesbroek, J. M., Coenen, M., DeCarli, C., Fletcher, E. M., Maillard, P. M., Initiative, A. D. N., Barkhof, F., Barnes, J., Benke, T., Chen, C. P. L. H., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13765 · Cited by 38 · see citing works
“Author disclosures are available in the Supporting Information.”
MethodThe association between white matter hyperintensities and amyloid and tau deposition
Alban, S. L., Lynch, K. M., Ringman, J. M., Toga, A. W., Chui, H. C., Sepehrband, F., & Choupan, J. (2023) · NeuroImage: Clinical · doi:10.1016/j.nicl.2023.103383 · Cited by 35 · see citing works
“Early stages of AD before severe symptom onset are associated with increased β -amyloid accumulation in the neocortex, regions which were significantly associated with WMHs in our analysis (Palmqvist et al. 2017, Thal et al. 2002, Moscoso et al. 2020).”
Regional associations of white matter hyperintensities and early cortical amyloid pathology
Lorenzini, L., Ansems, L. T., Lopes Alves, I., Ingala, S., Vállez García, D., Tomassen, J., Sudre, C., Salvadó, G., Shekari, M., Operto, G., et al. (2022) · Brain Communications · doi:10.1093/braincomms/fcac150 · Cited by 36 · see citing works
Schoemaker, D., Zotin, M. C. Z., Chen, K., Igwe, K. C., Vila‐Castelar, C., Martinez, J. E., Baena, A. Y., Fox‐Fuller, J. T., Lopera, F. J., Reiman, E. M., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01030-7 · Cited by 32 · see citing works
18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum
Moscoso, A., Silva‐Rodríguez, J., Aldrey, J. M., Cortés, J., Peleteiro, J. M. P., Ruibal, Á., Aguiar, P., & Initiative, A. D. N. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05493-y · Cited by 33 · see citing works
Sharp, F. R., DeCarli, C. S., Jin, L., & Zhan, X. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1096206 · Cited by 30 · see citing works
“The spatial distribution of WMH is associated with future amyloid accumulation in the cognitively normal elderly without PET-detectable amyloid pathology (Moscoso et al., 2020).”
BackgroundCogswell, P. M., Lundt, E. S., Therneau, T. M., Mester, C. T., Wiste, H. J., Graff‐Radford, J., Schwarz, C. G., Senjem, M. L., Gunter, J. L., Reid, R. I., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38878-8 · Cited by 29 · see citing works
Zheng, M., Liu, Z., Mana, L., Qin, G., Huang, S., Gong, Z., Tian, M., He, Y., & Wang, P. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114264 · Cited by 25 · see citing works
Shi, D., Xie, S., Li, A., Wang, Q., Guo, H., Han, Y., Xu, H., Gan, W., Zhang, L., Guo, T., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01899-w · Cited by 25 · see citing works
“Unlike a few reports [21, 23, 26], we found greater baseline WMH did not predict longitudinal cortical Aβ accumulation, neither lower baseline plasma Aβ42/Aβ40 nor higher cortical Aβ deposition predicted longitudinal WMH increase regardless of APOE-ε4 status.”
ResultProsser, L., MacDougall, A. M., Sudre, C. H., Manning, E. N., Malone, I. B., Walsh, P., Goodkin, O., Pemberton, H., Barkhof, F., Biessels, G. J., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000201572 · Cited by 25 · see citing works
“White matter hyperintensities (WMH) of presumed vascular origin and cerebral microbleeds (CMBs) are 2 such imaging features thought to represent different pathologic processes,(15) both associated with neurodegeneration.(16,17) HigherWMHburden at baseline is associated with later progression to MCI,(18) and increases…”
Cha, W.-J., Yi, D., Ahn, H., Byun, M. S., Chang, Y. Y., Choi, J.-M., Kim, K., Choi, H., Jung, G., Kang, K. M., et al. (2024) · Alzheimer's Research & Therapy · doi:10.1186/s13195-024-01417-8 · Cited by 20 · see citing works
“Additionally, in contrast to our result, another study which focused only on the influence of WMHs on Aβ change demonstrated that baseline WMH volume was significantly related with increase of cerebral Aβ deposition [19].”
ResultTan, C. H., Chew, J. L., Zhang, L., Gulyás, B. Z., & Chen, C. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.03.013 · Cited by 18 · see citing works
Recent Advances in Imaging of Preclinical, Sporadic, and Autosomal Dominant Alzheimer's Disease
Buckley, R. F. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01026-5 · Cited by 18 · see citing works
Moscoso, A., Grothe, M. J., Schöll, M., & Initiative, A. D. N. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05195-5 · Cited by 16 · see citing works
Twait, E. L., Min, B., Beran, M., Vonk, J. M. J., & Geerlings, M. I. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101952 · Cited by 14 · see citing works
White Matter Hyperintensity as a Vascular Contribution to the AT(N) Framework
Ng, K. P., shen, J., Chiew, H. J., Ng, A., Kandiah, N., Rosa‐Neto, P., & Gauthier, S. G. (2023) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2023.53 · Cited by 12 · see citing works
“003) were associated with faster amyloid accumulation (73).”
BackgroundWhite matter hyperintensity spatial patterns: Risk factors and clinical correlates
Beyer, F., Tsuchida, A., Soumaré, A., Rajula, H. S. R., Mishra, A., Crivello, F., Proust‐Lima, C., Loeffler, M., Tzourio, C., Amouyel, P., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70053 · Cited by 12 · see citing works
“64,65 Of note, posterior WMHs have also been associated with parenchymal brain amyloid deposition, 15,66 and a study in asymptomatic autosomal dominant AD mutation carriers found that occipital and parietal WMH volume increased two decades before symptom onset.”
Fischer, L., Parker, D. M., Maboudian, S. A., Fonseca, C. S., Tato-Fernández, C., Annen, L., Arunachalam, P., Bacci, J. R., Barboure, M., Capelli, S., et al. (2025) · Alzheimer's Research & Therapy · doi:10.1186/s13195-025-01920-6 · Cited by 11 · see citing works
“A longitudinal study over eight years showed that higher WMH burden is associated with an increase in Aβ accumulation in cognitively unimpaired individuals [127].”
Pham, N. T. T., Graff‐Radford, J., Machulda, M. M., Spychalla, A. J., Schwarz, C. G., Senjem, M. L., Lowe, V. J., Vemuri, P., Kantarci, K., Knopman, D. S., et al. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.07.008 · Cited by 10 · see citing works
Brown, S. S. G., Mak, E., Clare, I. C. H., Grigorova, M., Beresford‐Webb, J., Walpert, M., Jones, E., Hong, Y. T., Fryer, T. D., Coles, J., et al. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.02.013 · Cited by 9 · see citing works
Park, H. J., Lee, J. Y., Yang, J., Kim, H.-J., Kim, Y. S., Kim, J. Y., & Choi, Y. Y. (2023) · Journal of the Korean Society of Radiology · doi:10.3348/jksr.2022.0084 · Cited by 8 · see citing works
A deep semantic segmentation correction network for multi-model tiny lesion areas detection
Liu, Y., Xiang, L., Li, T., Li, B., Wang, Z., Gan, J., & Wei, B. (2021) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-021-01430-z · Cited by 8 · see citing works
Ali, D. G., Abner, E. L., Bahrani, A. A., El Khouli, R., Gold, B. T., Jiang, Y., Wilcock, D. M., & Jicha, G. A. (2023) · Brain Sciences · doi:10.3390/brainsci13020218 · Cited by 7 · see citing works
Ali, D. G., Bahrani, A. A., Khouli, R. H. E., Gold, B. T., Jiang, Y., Zachariou, V., Wilcock, D. M., & Jicha, G. A. (2023) · Brain and Behavior · doi:10.1002/brb3.3209 · Cited by 6 · see citing works
“…from epidemiological and clinical–pathological studies supporting the relationship between SVD and AD (Al-Janabi et al., 2018; Kim et al., 2016; Moscoso et al., 2020; Noh et al., 2014; Ortner et al., 2015; Yi et al., 2018), the mechanistic role of SVD in potentially contributing to the…”
Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden
Strain, J. F., Rahmani, M., Phuah, C., Dierker, D. L., Luo, J. R., Owen, C., Vlassenko, A. G., Jafri, H., Bourgeat, P., Fripp, J., et al. (2025) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2025.12.006 · Cited by 3 · see citing works
Amyloid and tau pathologies are drivers of white matter damage in aging and Alzheimer’s disease
Kamal, F., & Dadar, M. (2026) · GeroScience · doi:10.1007/s11357-026-02357-x · Cited by 3 · see citing works
Lin, Z., Hong, Y., Hu, Y., Xiao, Q., Peng, S., Wu, D., Guo, T., & Jiang, D. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70990 · Cited by 2 · see citing works
Misra, A., Wang, Y., Taheri, M. R., Chiang, G. C.-Y., & Cho, J. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1754415 · Cited by 2 · see citing works
“…microvascular damage, and axonal loss all of which can contribute to reduced OEF due to impaired neuronal and vascular coupling (Alban et al., 2023; Alber et al., 2019; Brickman and Rizvi, 2023; Garnier-Crussard et al., 2022; Laing et al., 2020; McAleese et al., 2021; Moscoso et al., 2020).”
Hong, H., Chen, Y., Liu, W., Luo, X., Zhang, M., & Initiative, A. D. N. (2024) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12585 · Cited by 1 · see citing works
PSEN2 Mutations May Mimic Frontotemporal Dementia: Two New Case Reports and a Review
Pereiro, A. M. M., Castro, B. Q., Ouro, A., Aldrey, J. M., Hernández, J. C., Aramburu-Núñez, M., Arias, M., Martín, I. J., Sobrino, T., & Peleteiro, J. M. P. (2024) · Biomedicines · doi:10.3390/biomedicines12081881 · Cited by 1 · see citing works
“…of mutations that give rise to familial Alzheimer’s disease and, more particularly, those of PSEN2 in the development of cerebral amyloid angiopathy (CAA), there are several reports of patients in whom intracranial hemorrhages were described, mostly in the cohort with the p.Asn141Ile mutation [36].”
BackgroundGuo, F., Sheng, Z.-H., Li, T., Huang, L.-Y., Li, B., Wang, X.-J., & Initiative, A. D. N. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877251415349 · Cited by 1 · see citing works
“15 Furthermore, recent work indicates that amyloid-β (A β ) deposition and WMH have additive and synergistic effects on cognitive decline, 16 suggesting interplay between amyloid and small-vessel processes.”
Association between Cerebral Small Vessel and Alzheimer’s Disease
Lee, K. H., & Kang, K. M. (2022) · Journal of the Korean Society of Radiology · doi:10.3348/jksr.2022.0041 · Cited by 1 · see citing works
“2020 (70) Tau CSF t-tau Significant† Tosto et al.”
BackgroundKhasayeva, N., Jensen, K. M., Eierud, C., Petropoulos, H., Calhoun, V. D., & Iraji, A. (2025) · IEEE International Symposium on Biomedical Imaging (ISBI) · doi:10.1109/isbi60581.2025.10981043
Cha, W., Yi, D., Ahn, H., Byun, M. S., Chang, Y. Y., Choi, J.-M., Kim, K., Choi, H., Jung, G., Kang, K. M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25367341
Zhang, Y., Luo, X., Hong, H., Zhang, R., Wang, S., Liu, L., Lin, M., Li, K., Zeng, Q., Chen, Y., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.71022
Ba, W., Bao, C., Gong, Y., Liu, Z., Yang, J., Li, Y., & Initiative, A. D. N. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261482151
“5,19,20 In addition, the relationship between the trajectory changes of longitudinal WMH and A β and tau remains unclear.”
- Authors
- Moscoso, A., Rey-Bretal, D., Silva-Rodríguez, J., Aldrey, J. M., Cortés, J., Pías-Peleteiro, J., Ruibal, Á., & Aguiar, P.
- Affiliations
- Universidade de Santiago de Compostela (ES)
- Complejo Hospitalario Universitario de Santiago (ES)
- Corresponding author
- Aguiar, Pablo
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 218
- Pages
- 116944
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W3027270139
- Cited by
- 49
- References
- 58
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 10 · 2020: 2
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- GE Healthcare
- Genentech
- H. Lundbeck A/S
- Alzheimer's Disease Neuroimaging Initiative
- Johnson and Johnson
- IXICO
- National Institutes of Health (U01 AG024904)
- Northern California Institute for Research and Education
- Merck
- U.S. Department of Defense (W81XWH-12-2-0012)
- Federación Española de Enfermedades Raras (EAPA_791/2018-NEUROATLANTIC, RYC-2015/17430)
- Janssen Research and Development
- Instituto de Salud Carlos III
- University of Southern California
- National Institute of Biomedical Imaging and Bioengineering (PI16/01416)
- Fujirebio Europe
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- white matter hyperintensities, cognitively normal elderly, partial volume correction, cingulate cortex, Alzheimer's disease prevention
- MeSH terms
- Aged, Aged, 80 and over, Aging, Amyloid, Cross-Sectional Studies, False Positive Reactions, Female, Frontal Lobe, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Parietal Lobe, Reference Values, Positron-Emission Tomography, Leukoaraiosis, White Matter
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