Structural brain changes in normal individuals with a maternal history of Alzheimer's
Open accessAbstract
Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH-) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH-, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH- in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH- and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cognitively intact children of AD mothers, relative to children of AD fathers, show greater age-associated brain atrophy, faster longitudinal brain atrophy, increased Aβ plaque deposition, elevated CSF oxidative stress markers, and AD-like CSF Aβ changes.
“Subsequent studies found that the cognitively intact children of AD mothers, relative to the cognitively intact children of AD fathers, show greater degrees of age-associated brain atrophy, faster rates of longitudinal brain atrophy, increased Aβ plaque deposition, elevated cerebrospinal fluid (CSF) oxidative stress markers, and AD-like CSF Aβ changes [130-137].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [130]
Maternal inheritance appears to determine several AD endophenotypes.
“Maternal inheritance appears to determine several AD endophenotypes.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [130]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798 · see citing works
Voxel-Based Morphometry—The Methods
Ashburner, J., & Friston, K. J. (2000) · NeuroImage · doi:10.1006/nimg.2000.0582 · Cited by 8,676 · see citing works
Co-planar stereotaxic atlas of the human brain
Laitinen, L. (1989) · Clinical Neurology and Neurosurgery · doi:10.1016/0303-8467(89)90128-5 · Cited by 7,565 · see citing works
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Maldjian, J., Laurienti, P., Kraft, R., & Burdette, J. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00169-1 · Cited by 5,453 · see citing works
A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains
Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N. A., Friston, K. J., & Frackowiak, R. S. J. (2001) · NeuroImage · doi:10.1006/nimg.2001.0786 · Cited by 4,561 · see citing works
Region of interest analysis using an SPM toolbox
Brett, M. (2002) · NeuroImage · Cited by 2,273 · see citing works
Alzheimer’s Disease Neuroimaging Initiative
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W. J., Trojanowski, J. Q., Toga, A. W., & Beckett, L. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-72076-0_18 · Cited by 1,493 · see citing works
A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Chételat, G., Landeau, B., Eustache, F., Mézenge, F., Viader, F., de la Sayette, V., Desgranges, B., & Baron, J.-C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.05.015 · Cited by 526 · see citing works
Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI
Jack, C. R., Shiung, M. M., Weigand, S. D., O’Brien, P. C., Gunter, J. L., Boeve, B. F., Knopman, D. S., Smith, G. E., Ivnik, R. J., Tangalos, E. G., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000180958.22678.91 · Cited by 492 · see citing works
Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve
Querbes, O., Aubry, F., Pariente, J., Lotterie, J.-A., Démonet, J., Duret, V., Puel, M., Berry, I., Fort, J., Celsis, P., et al. (2009) · Brain · doi:10.1093/brain/awp105 · Cited by 438 · see citing works
Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease
Green, R. C. (2002) · JAMA · doi:10.1001/jama.287.3.329 · Cited by 391 · see citing works
Convit, A., de Asis, J., de Leon, M. J., Tarshish, C. Y., De Santi, S., & Rusinek, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00107-4 · Cited by 359 · see citing works
Self-citationWhitwell, J. L., Crum, W. R., Watt, H., & Fox, N. C. (2001) · PubMed Central · Cited by 357 · see citing works
Voxel-based morphometry to discriminate early Alzheimer's disease from controls
Hirata, Y., Matsuda, H., Nemoto, K., Ohnishi, T., Hirao, K., Yamashita, F., Asada, T., Iwabuchi, S., & Samejima, H. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.03.038 · Cited by 329 · see citing works
Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study
Karas, G. B., Scheltens, P., Rombouts, S. A. R. B., van Schijndel, R. A., Klein, M., Jones, B. F., van der Flier, W. M., Vrenken, H., & Barkhof, F. (2007) · Neuroradiology · doi:10.1007/s00234-007-0269-2 · Cited by 292 · see citing works
Volume reduction of the entorhinal cortex in subjective memory impairment
Jessen, F., Feyen, L., Freymann, K., Tepest, R., Maier, W., Heun, R., Schild, H. H., & Scheef, L. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.10.010 · Cited by 276 · see citing works
Longitudinal MRI atrophy biomarkers: Relationship to conversion in the ADNI cohort
Risacher, S. L., Shen, L., West, J. D., Kim, S., McDonald, B. C., Beckett, L. A., Harvey, D. J., Jack, C. R., Weiner, M. W., & Saykin, A. J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.029 · Cited by 276 · see citing works
Leukoencephalopathy in normal and pathologic aging: 1. CT of brain lucencies.
GEORGE, A. E., de Leon, M. J., Gentes, C., Miller, J., London, E., Budzilovich, G. N., Ferris, S. H., & Chase, N. (1986) · PubMed Central · Cited by 273 · see citing works
Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease
Reiman, E. M., Uecker, A., Caselli, R. J., Lewis, S., Bandy, D., De Leon, M. J., De Santi, S., Convit, A., Osborne, D., Weaver, A., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440226 · Cited by 266 · see citing works
Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism
Mosconi, L., Brys, M., Switalski, R., Mistur, R., Glodzik, L., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705036104 · Cited by 237 · see citing works
Self-citationA Validation Study of the Dementia Questionnaire
Kawas, C. H., Segal, J., Stewart, W. F., Corrada, M. M., & Thal, L. J. (1994) · Archives of Neurology · doi:10.1001/archneur.1994.00540210073015 · Cited by 231 · see citing works
Subregional neuroanatomical change as a biomarker for Alzheimer's disease
Holland, D., Brewer, J. B., Hagler, D. J., Fennema-Notestine, C., Dale, A. M., Initiative, T. A. D. N., Weiner, M., Thal, L., Petersen, R., Jack, C. R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906053106 · Cited by 210 · see citing works
Self-citationMosconi, L., Mistur, R., Switalski, R., Brys, M., Glodzik, L., Rich, K., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2009) · Neurology · doi:10.1212/01.wnl.0000333247.51383.43 · Cited by 188 · see citing works
Self-citationCupples, L. A., Farrer, L. A., Sadovnick, A. S. D., Relkin, N. R., Whitehouse, P. J., & Green, R. C. (2004) · Genetics in Medicine · doi:10.1097/01.gim.0000132679.92238.58 · Cited by 166 · see citing works
Assessing the onset of structural change in familial Alzheimer's disease
Schott, J. M., Fox, N. C., Frost, C. D., Scahill, R. I., Janssen, J. C., Chan, D., Jenkins, R., & Rossor, M. N. (2002) · Annals of Neurology · doi:10.1002/ana.10424 · Cited by 160 · see citing works
Edland, S. D., Silverman, J. M., Peskind, E. R., Tsuang, D., Wijsman, E., & Morris, J. C. (1996) · Neurology · doi:10.1212/wnl.47.1.254 · Cited by 145 · see citing works
[Alzheimer's disease Neuroimaging Initiative (ADNI)].
Iwatsubo, T. (2011) · PubMed · Cited by 141 · see citing works
Mosconi, L., Rinne, J. O., Tsui, W. H., Berti, V., Li, Y., Wang, H., Murray, J., Scheinin, N., Någren, K., Williams, S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914141107 · Cited by 135 · see citing works
Self-citationVoxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment
Hämäläinen, A., Tervo, S., Grau-Olivares, M., Niskanen, E. I., Pennanen, C., Huuskonen, J., Kivipelto, M., Hänninen, T., Tapiola, M., Vanhanen, M., et al. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.06.016 · Cited by 134 · see citing works
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124 · cited 1× · see citing works
“Several studies have shown that having a family history of LOAD is a major risk factor for developing the disease among cognitively normal (NL) individuals (Farrer et al., 1997).”
BackgroundA comparison of familial and sporadic Alzheimer's disease
Duara, R., Lopez-Alberola, R. F., Barker, W. W., Loewenstein, D. A., Zatinsky, M., Eisdorfer, C. E., & Weinberg, G. B. (1993) · Neurology · doi:10.1212/wnl.43.7.1377 · Cited by 122 · see citing works
Correlations Between Apolipoprotein E ε4 Gene Dose and Whole Brain Atrophy Rates
Chen, K., Reiman, E. M., Alexander, G. E., Caselli, R. J., Gerkin, R. D., Bandy, D. J., Domb, A., Osborne, D., Fox, N. C., Crum, W. R., et al. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.916 · Cited by 118 · see citing works
Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease
Honea, R. A., Swerdlow, R. H., Vidoni, E. D., Goodwin, J., & Burns, J. M. (2010) · Neurology · doi:10.1212/wnl.0b013e3181c918cb · Cited by 106 · see citing works
Furlong, R. A., Ho, L. W., Rubinsztein, J. S., Walsh, C., Paykel, E. S., & Rubinsztein, D. C. (1999) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19990820)88:4 · Cited by 100 · see citing works
Alzheimer’s Disease: In Vivo Detection of Differential Vulnerability of Brain Regions
deToledo‐Morrell, L., Sullivan, M., Morrell, F., Wilson, R. S., Bennett, D. A., & Spencer, S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00114-0 · Cited by 91 · see citing works
CT changes in dementing diseases.
Babikian, V. L., & Kase, C. S. (1987) · PubMed · Cited by 88 · see citing works
Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes
Mosconi, L., Berti, V., Swerdlow, R. H., Pupi, A., Duara, R., & de Leon, M. (2010) · Human Genomics · doi:10.1186/1479-7364-4-3-170 · Cited by 85 · see citing works
Self-citationSelective Disruption of the Cerebral Neocortex in Alzheimer's Disease
Desikan, R. S., Sabuncu, M. R., Schmansky, N. J., Reuter, M., Cabral, H., Hess, C. P., Weiner, M. W., Biffi, A., Anderson, C. D., Rosand, J. M., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012853 · Cited by 85 · see citing works
Santi, S. D., Pirraglia, E., Barr, W., Babb, J. S., Williams, S., Rogers, K., Glodzik, L., Bryś, M., Mosconi, L., Reisberg, ., et al. (2008) · Neuropsychology · doi:10.1037/0894-4105.22.4.469 · Cited by 81 · see citing works
Self-citationWhitwell, J. L., & Jack, C. R. (2005) · Topics in Magnetic Resonance Imaging · doi:10.1097/01.rmr.0000245457.98029.e1 · Cited by 80 · see citing works
Variability of Familial Risk of Alzheimer Disease Across the Late Life Span
Silverman, J. M., Ciresi, G., Smith, C. J., Marin, D. B., & Beeri, M. S. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.5.565 · Cited by 80 · see citing works
Association of parental dementia with cognitive and brain MRI measures in middle-aged adults
Debette, S., Wolf, P. A., Beiser, A., Au, R., Himali, J. J., Pikula, A., Auerbach, S. H., DeCarli, C. S., & Seshadri, S. S. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67833 · Cited by 77 · see citing works
State-specific projections through 2025 of Alzheimer disease prevalence
Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D., & Evans, D. A. (2004) · Neurology · doi:10.1212/01.wnl.0000123018.01306.10 · Cited by 77 · see citing works
Locke, P. A., Conneally, P. M., Tanzi, R. E., Gusella, J. F., & Haines, J. L. (1995) · Genetic Epidemiology · doi:10.1002/gepi.1370120108 · Cited by 75 · see citing works
Effects of ApoE4 and maternal history of dementia on hippocampal atrophy
Andrawis, J. P., Hwang, K. S., Green, A. E., Kotlerman, J., Elashoff, D., Morra, J. H., Cummings, J. L., Toga, A. W., Thompson, P. M., & Apostolova, L. G. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.07.020 · Cited by 54 · see citing works
Variability of age at onset in siblings with familial Alzheimer disease
Gómez-Tortosa, E., Barquero, M. S., Barón, M., Sainz, M. J., Manzano, S., Payno, M., Ros, R., Almaraz, C., Gómez-Garré, P., & Jiménez-Escrig, A. (2007) · Archives of Neurology · doi:10.1001/archneur.64.12.1743 · Cited by 47 · see citing works
Measurement of medial temporal lobe atrophy in diagnosis of Alzheimer's disease
de Leon, M. J., Golomb, J. B., Convit, A. J., DeSanti, S., McRae, T. D., GEORGE, A. E., Jobst, K. A., & Smith, A. D. (1993) · The Lancet · doi:10.1016/0140-6736(93)92610-6 · Cited by 39 · see citing works
Self-citationGinestroni, A., Battaglini, M., Nave, R. D., Moretti, M., Tessa, C., Giannelli, M., Caffarra, P., Nacmias, B., Bessi, V., Sorbi, S., et al. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5044-3 · Cited by 34 · see citing works
Besga, A., Ortiz, L. O., Fernández, A., Maestú, F., Arrazola, J., Gil‐Gregorio, P., Fuentes, M. E., & Ortiz, T. (2010) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3181aba730 · Cited by 28 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- George AE De Leon MJ Kalnin A Rosner L Goodgold A Chase N Leukoencephalopathy in normal and pathologic aging: 2. MRI and brain lucencies. Am. J. Neuroradiol 1986 7 567 570 3088934 PMC8334676
Cited by
Sorted by citations
Mitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Uddin, M. S., Rahman, M. M., Jakaria, M., Rahman, M. S., Hossain, M. S., Islam, A., Ahmed, M., Mathew, B., Omar, U. M., Barreto, G. E., et al. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01911-8 · Cited by 156 · see citing works
Zhao, L., Mao, Z., Woody, S. K., & Brinton, R. D. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.011 · Cited by 132 · see citing works
Mak, E., Gabel, S., Mirette, H., Su, L., Williams, G. B., Waldman, A., Wells, K., Ritchie, K., Ritchie, C., & O’Brien, J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.001 · Cited by 71 · see citing works
H. Swerdlow, R. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072535 · Cited by 35 · see citing works
Heneghan, A., Deng, F., Wells, K., Ritchie, K., Muniz-Terrera, G., Ritchie, C. W., Lawlor, B., & Naci, L. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-220267 · Cited by 18 · see citing works
Mitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2 · see citing works
- Authors
- Berti, V., Mosconi, L., Glodzik, L., Li, Y., Murray, J., De Santi, S., Pupi, A., Tsui, W., & De Leon, M. J.
- Affiliations
- University of Florence (IT)
- New York University (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Mosconi, Lisa
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 32
- Issue
- 12
- Pages
- 2325.e17-2325.e26
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC3115436
- OpenAlex
- W2030466325
- Cited by
- 58
- References
- 52
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- NIH-NIA
- NIH-NCRR (AG035137, AG032554, AG13616, AG12101, AG08051, AG022374, MO1RR0096)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- late-onset Alzheimer's disease, family history of Alzheimer's disease, maternal inheritance, gray matter volume, precuneus, parent-of-origin effects, preclinical biomarkers, cognitively normal individuals, apolipoprotein E
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mothers, Prospective Studies, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
