The most common cause of severe cognitive impairment in adults is Alzheimer’s disease (AD). Depending on the age of onset, AD is divided into early (<65 years) and late (≥65 years) forms. Early-onset AD (EOAD) is significantly less common than late-onset AD, accounting for only about 5–10% of cases. However, its medical and social significance as a disease leading to loss of ability to work and legal capacity, as well as premature death in patients aged 40–64 years, is extremely high. Patients with EOAD, as compared with late-onset AD (LOAD), have a greater number of atypical clinical variants: 25% and 6–12.5%, respectively, which complicates the differential diagnosis of EOAD against other neurodegenerative diseases. Nonetheless, the typical amnestic variant predominates in both LOAD and EOAD. Also, patients with EOAD have characteristic neuroimaging features: brain MRI scans from patients with EOAD often have more severe parietal atrophy and less severe hippocampal atrophy than those from patients with LOAD. This report addresses the features of the clinical and neuroimaging picture in patients with EOAD. A clinical case of a patient with EOAD is presented.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
M. W. Bondi, E. C. Edmonds, and D. P. Salmon, “Alzheimer’s Disease: Past, present, and future,” J. Int. Neuropsychol. Soc., 23, No. 9–10, 818–831 (2017), https://doi.org/10.1017/S135561771700100X.
M. I. Kamboh, “Genomics and functional genomics of Alzheimer’s disease,” Neurotherapeutics, 19, No. 1, 152–172 (2022), https://doi.org/10.1007/s13311-021-01152-0.
T. Ayodele, E. Rogaeva, J. T. Kurup, et al., “Early-onset Alzheimer’s disease: What is missing in research?” Curr. Neurol. Neurosci. Rep., 21, No. 2, 4 (2021), https://doi.org/10.1007/s11910-020-01090-y.
A. S. Vogt, G. T. Jennings, M. O. Mohsen, et al., “Alzheimer’s disease: A brief history of immunotherapies targeting β-amyloid,” Int. J. Mol. Sci., 15 24(4, 3895 (2023), https://doi.org/10.3390/ijms24043895.
A. B. Lokshina, D. A. Grishina, and A. V. Obukhova, “Early-onset Alzheimer’s disease,” Nevrol. Neiropsikh. Psikhosom., 14, No. 2, 110–116 (2022), https://doi.org/10.14412/2074-2711-2022-2-110-116.
I. S. Barber, A. Braae, N. Clement, et al., “Mutation analysis of sporadic early-onset Alzheimer’s disease using the NeuroX array,” Neurobiol. Aging, 49, 215–215 (2017), https://doi.org/10.1016/j.neurobiolaging.2016.09.008.
R. Cacace, K. Sleegers, and C. Van Broeckhoven, “Molecular genetics of early-onset Alzheimer’s disease revisited,” Alzheimers Dement., 12, No. 6, 733–748 (2016), https://doi.org/10.1016/j.jalz.2016.01.012.
M. H. Dai, H. Zheng, L. D. Zeng, et al., “The genes associated with early-onset Alzheimer’s disease,” Oncotarget, 9, 15132–15143 (2018), https://doi.org/10.18632/oncotarget.23738.
K. Maurer, S. Volk, and H. Gerbaldo, “Auguste D and Alzheimer’s disease,” Lancet, 349, No. 9064, 1546–1549 (1997), https://doi.org/10.1016/S0140-6736(96)10203-8.
N. N. Koberskaya and N. A. Koval’chuk, “Early-onset Alzheimer’s disease,” Meditsinsk. Sov., No. 1, 10–16 (2019), https://doi.org/10.21518/2079-701X-2019-1-10-16.
I. V. Litvinenko, A. Yu. Emelin, Lobzin V. Yu., et al., “Amyloid hypothesis of Alzheimer’s disease: past and present, hopes and disappointments,” Nevrol. Neiropsikh. Psikhosom., 11, No. 3, 4–10 (2019), https://doi.org/10.14412/2074-2711-2019-3-4-10.
D. W. Sirkis, L. W. Bonham, T. P. Johnson, et al., “Dissecting the clinical heterogeneity of early-onset Alzheimer’s disease,” Mol. Psychiatry, 27, No. 6, 2674–2688 (2022), https://doi.org/10.1038/s41380-022-01531-9.
M. A. Lambert, H. Bickel, et al., “Estimating the burden of early onset dementia; systematic review of disease prevalence,” Eur. J. Neurol., 21, No. 4, 563–569 (2014), https://doi.org/10.1111/ene.12325.
E. Renvoize, M. Hanson, and M. Dale, “Prevalence and causes of young onset dementia in an English health district,” Int. J. Geriatr. Psychiatry, 26, No. 1, 106–107 (2011), https://doi.org/10.1002/gps.2456.
M. F. Mendez, “Early-onset Alzheimer disease,” Neurol. Clin., 35, No. 2, 263–281 (2017), https://doi.org/10.1016/j.ncl.2017.01.005.
T. S. Wingo, J. J. Lah, A. I. Levey, et al., “Autosomal recessive causes likely in early-onset Alzheimer disease,” Arch. Neurol., 69, No. 1, 59–64 (2012), https://doi.org/10.1001/archneurol.2011.221.
A. I. Jarmolowicz, H. Y. Chen, and P. K. Panegyres, “The patterns of inheritance in early-onset dementia: Alzheimer’s disease and frontotemporal dementia,” Am. J. Alzheimers Dis. Other Dement., 30, No. 3, 299–306 (2015), https://doi.org/10.1177/1533317514545825.
D. Campion, C. Dumanchin, D. Hannequin, et al., “Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum,” Am. J. Hum. Genet., 65, No. 3, 664–670 (1999), https://doi.org/10.1086/302553.
K. A. Bates, G. Verdile, Q. X. Li, et al., “Clearance mechanisms of Alzheimer’s amyloid-beta peptide: implications for therapeutic design and diagnostic tests,” Mol. Psychiatry, 14, No. 5, 469–486 (2009), https://doi.org/10.1038/mp.2008.96.
C. Reitz, E. Rogaeva, Beecham, G. W., “Late-onset vs nonmendelian early-onset Alzheimer disease: A distinction without a difference?” Neurol. Genet., 6, No. 5, 512 (2020), https://doi.org/10.1212/NXG.0000000000000512.
N. Lopez-Riquelme, J. Alom-Poveda, et al., “Apolipoprotein E epsilon4 allele and malondialdehyde level are independent risk factors for Alzheimer’s disease,” SAGE Open Med., 4, 2050312115626731 (2016), https://doi.org/10.1177/2050312115626731.
E. Genin, D. Hannequin, D. Wallon, et al., “APOE and Alzheimer disease: a major gene with semi-dominant inheritance,” Mol. Psychiatry, 16, 903–907 (2011), https://doi.org/10.1038/mp.2011.52.
G. Nicolas, C. Charbonnier, D. Wallon, et al., “SORL1 rare variants: a major risk factor for familial early-onset Alzheimer’s disease,” Mol. Psychiatry, 21, No. 6, 831–836 (2016), https://doi.org/10.1038/mp.2015.121.
J. Verheijen, T. Van den Bossche, J. van der Zee, et al., “A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer’s disease,” Acta Neuropathol., 132, No. 2, 213–224 (2016), https://doi.org/10.1007/s00401-016-1566-9.
C. Pottier, D. Wallon, S. Rousseau, et al., “TREM2 R47H variant as a risk factor for early-onset Alzheimer’s disease,” J. Alzheimers Dis., 35, 45–59(2013).
B. Jiao, H. Liu, L. Guo, et al., “The role of genetics in neurodegenerative dementia: a large cohort study in South China,” NPJ Genom. Med., 6, 69 (2021), https://doi.org/10.1038/s41525-021-00235-3.
Yu. A. Shpilyukova, A. O. Protopopova, N. Yu Abramycheva, et al., “Early-onset rapidly-progressing dementia associated with the I143T mutations in the PSEN1 gene: a clinical case in a Russian family,” Nevrol. Neiropsikh. Psikhosom., 15, No. 2, 63–67 (2023), https://doi.org/10.14412/2074-2711-2023-2-63-67.
D. B. Hammers, A. Eloyan, A. Taurone, et al., “Profiling baseline performance on the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) cohort near the midpoint of data collection,” Alzheimers Dement., 19, No. 9, 8–18 (2023), https://doi.org/10.1002/alz.13399.
M. F. Mendez, A. S. Lee, A. Joshi, et al., “Nonamnestic presentations of early-onset Alzheimer’s disease,” Am. J. Alzheimers Dis. Other Demen., 27, 413–420 (2012), https://doi.org/10.1177/1533317512454711.
R. J. Bateman, P. S. Aisen, B. De Strooper, et al., “Autosomaldominant Alzheimer’s disease: a review and proposal for the prevention of Alzheimer’s disease,” Alzheimers Res. Ther., 3, No. 1, 1 (2011), https://doi.org/10.1186/alzrt59.
E. L. Koedam, V. Lauffer, A. E. van der Vlies, et al., “Early-versus late-onset Alzheimer’s disease: more than age alone,” J. Alzheimers Dis., 19,1401–1408 (2010).
A. Yu. Emelin, M. M. Odinak, V. Yu. Lobzin, and A. A. Galaeva, “Alzheimer’s disease as a heterogeneous disease,” Izv. Ross. Voenno-Med. Akad., 40, S4, 37–41 (2021).
D. Lei, C. Mao, J. Li, et al., “CSF biomarkers for early-onset Alzheimer’s disease in Chinese population from PUMCH dementia cohort,” Front. Neurol., 9, No. 13, 1030019 (2023), https://doi.org/10.3389/fneur.2022.1030019.
M. F. Mendez, “Early-onset Alzheimer disease and its variants,” Continuum (Minneap. Minn.), 25, No. 1, 34–51 (2019), https://doi.org/10.1212/CON.0000000000000687.
C. Wattmo and A. K. Wallin, “Early-versus late-onset Alzheimer’s disease in clinical practice: cognitive and global outcomes over 3 years,” Alzheimers Res. Ther., 9, No. 1, 70 (2017), https://doi.org/10.1186/s13195-017-0294-2.
P. Hermann and I. Zerr, “Rapidly progressive dementias – aetiologies, diagnosis and management,” Nat. Rev. Neurol., 18, No. 6, 363–376 (2022), https://doi.org/10.1038/s41582-022-00659-0.
N. Chitravas, R. S. Jung, D. M. Kofskey, et al., “Treatable neurological disorders misdiagnosed as Creutzfeldt–Jakob disease,” Ann. Neurol., 70, No. 3, 437–444 (2011), https://doi.org/10.1002/ana.22454.
L. Peckeu, N. Delasnerie-Lauprètre, J. P. Brandel, et al., “Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt–Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009,” Euro. Surveill., 22, No. 41, 16-00715 (2017), https://doi.org/10.2807/1560-7917.ES.2017.22.41.16-00715.
G. S. Day, E. S. Musiek, and J. C. Morris, “Rapidly progressive dementia in the outpatient clinic: More than prions,” Alzheimer Dis. Assoc. Disord., 32, No. 4, 291–297 (2018), https://doi.org/10.1097/WAD.0000000000000276.
A. K. Wallin, K. Blennow, H. Zetterberg, et al., “CSF biomarkers predict a more malignant outcome in Alzheimer disease,” Neurology, 74, No. 19, 1531–1537 (2010), https://doi.org/10.1212/WNL.0b013e3181dd4dd8.
C. Schmidt, S. Haïk, K. Satoh, et al., “Rapidly progressive Alzheimer’s disease: a multicenter update,” J. Alzheimers Dis., 30, No. 4, 751–756 (2012).
G. Tosto, M. Gasparini, A. M. Brickman, et al., “Neuropsychological predictors of rapidly progressive Alzheimer’s disease,” Acta Neurol. Scand., 132, No. 6, 417–422 (2015), https://doi.org/10.1111/ane.12415.
K. Moschetti, N. Barragan, R. Basurto-Davila, et al., “Mortality and productivity losses from Alzheimer disease among us adults aged 40 to 64 years, 1999 to 2010,” Alzheimer Dis. Assoc. Disord., 29, No. 2, 165–168 (2015), https://doi.org/10.1097/WAD.0000000000000017.
K. Stanley and Z. Walker, “Do patients with young onset Alzheimer’s disease deteriorate faster than those with late onset Alzheimer’s disease? A review of the literature,” Int. Psychogeriatr., 26, No. 12, 1945–1953 (2014), https://doi.org/10.1017/S1041610214001173.
A. A. Gerritsen, C. Bakker, F. R. Verhey, et al., “Prevalence of comorbidity in patients with young-onset Alzheimer disease compared with late-onset: a comparative cohort study,” J. Am. Med. Dir. Assoc., 17, No. 4, 318–323 (2016), https://doi.org/10.1016/j.jamda.2015. 11.011.
Y. Chen, A. R. Sillaire, J. Dallongeville, et al., “Low prevalence and clinical effect of vascular risk factors in early-onset Alzheimer’s disease,” J. Alzheimers Dis., 60, No. 3, 1045–1054 (2017).
A. Palasi, B. Gutierrez-Iglesias, M. Alegret, et al., “Differentiated clinical presentation of early and late-onset Alzheimer’s disease: is 65 years of age providing a reliable threshold?” J. Neurol., 262, No. 5, 1238–1246 (2015), https://doi.org/10.1007/s00415-015-7698-3.
S. Joubert, N. Gour, E. Guedj, et al., “Early-onset and late-onset Alzheimer’s disease are associated with distinct patterns of memory impairment,” Cortex, 74, 217–22 (2016), https://doi.org/10.1016/j.cortex.2015.10.014.
N. N. Koberskaya, “Difficulties in differential diagnosis of early-onset Alzheimer’s disease (clinical cases),” Nervnye Bolezni, 3, 46–52 (2023), https://doi.org/10.24412/2226-0757-2023-13006.
R. Migliaccio, F. Agosta, K. L. Possin, et al., “Mapping the progression of atrophy in early- and late-onset Alzheimer’s disease,” J. Alzheimers Dis., 46, No. 2, 351–364 (2015).
H. Cho, S. Jeon, S. J. Kang, et al., “Longitudinal changes of cortical thickness in early- versus late-onset Alzheimer’s disease,” Neurobiol. Aging, 34, No. 7, 9–15 (2013), https://doi.org/10.1016/j.neurobiolaging.2013.01.004.
F. Loreto, A. Gontsarova, G. Scott, et al., “Visual atrophy rating scales and amyloid PET status in an Alzheimer’s disease clinical cohort,” Ann. Clin. Transl. Neurol., 10, No. 4, 619–631 (2023), https://doi.org/10.1002/acn3.51749.
S. J. Enkirch, A. Traschütz, A. Müller, et al., “The ERICA score: An MR imaging-based visual scoring system for the assessment of entorhinal cortex atrophy in Alzheimer disease,” Radiology, 288, No. 1, 226–333 (2018), https://doi.org/10.1148/radiol.2018171888.
K. M. Igarashi, “Entorhinal cortex dysfunction in Alzheimer’s disease,” Trends Neurosci., 46, No. 2, 124–136 (2023), https://doi.org/10.1016/j.tins.2022.11.006.
G. Karas, P. Scheltens, S. Rombouts, et al., “Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study,” Neuroradiology, 49, No. 12, 967–976 (2007), https://doi.org/10.1007/s00234-007-0269-2.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 124, No. 4, Iss. 2, pp. 56–63, April, 2024.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Kovalenko, E.A., Makhnovich, E.V., Bogolepova, A.N. et al. Characteristics of the Clinical and Neuroimaging Picture in Patients with Early-Onset Alzheimer’s Disease. Neurosci Behav Physi 54, 852–858 (2024). https://doi.org/10.1007/s11055-024-01680-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-024-01680-0