DIAGNOSTIC CHALLENGES AND CARE PATHWAYS IN YOUNG-ONSET DEMENTIA – A NARRATIVE REVIEW
Abstract
Young-onset dementia (YOD), defined as the onset of dementia symptoms before the age of 65, is a clinically and diagnostically complex condition that significantly impacts patients and families during peak social and economic stages of life. Compared to late-onset dementia, YOD more frequently presents with atypical features such as personality changes, executive dysfunction, psychiatric symptoms, or language impairments, often leading to delayed diagnosis and misclassification as primary psychiatric disorders. This narrative review provides a comprehensive overview of current evidence on the etiology, clinical presentation, diagnostic workup, and management of YOD. Alzheimer’s disease and frontotemporal dementia are the most common neurodegenerative causes, though a broad differential including autoimmune, infectious, metabolic, and hereditary disorders must be considered. Improving clinician awareness and access to age-appropriate diagnostic services is critical to reducing diagnostic delays and improving quality of life for individuals affected by YOD.
Aim of study: The aim of this study is to provide a comprehensive and updated overview of YOD, focusing on its diverse etiologies, clinical presentations, diagnostic challenges, and current management strategies. By synthesizing evidence from recent literature, the study seeks to offer practical guidance for clinicians in improving the timely recognition, differential diagnosis, and multidisciplinary care of individuals affected by YOD.
References
Armstrong, M. J., & Miyasaki, J. M. (2012). Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease [RETIRED]: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology, 79(6), 597–603. https://doi.org/10.1212/WNL.0b013e318263c443
Bennett, S., Shand, S., & Liddle, J. (2011). Occupational therapy practice in Australia with people with dementia: A profile in need of change: OCCUPATIONAL THERAPY FOR PEOPLE WITH DEMENTIA. Australian Occupational Therapy Journal, 58(3), 155–163. https://doi.org/10.1111/j.1440-1630.2011.00930.x
Birks, J. S. (2006). Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database of Systematic Reviews, 2016(3). https://doi.org/10.1002/14651858.CD005593
Blennow, K., & Zetterberg, H. (2018). Biomarkers for Alzheimer’s disease: Current status and prospects for the future. Journal of Internal Medicine, 284(6), 643–663. https://doi.org/10.1111/joim.12816
Clare, L., Linden, D. E. J., Woods, R. T., Whitaker, R., Evans, S. J., Parkinson, C. H., Van Paasschen, J., Nelis, S. M., Hoare, Z., Yuen, K. S. L., & Rugg, M. D. (2010). Goal-Oriented Cognitive Rehabilitation for People With Early-Stage Alzheimer Disease: A Single-Blind Randomized Controlled Trial of Clinical Efficacy. The American Journal of Geriatric Psychiatry, 18(10), 928–939. https://doi.org/10.1097/JGP.0b013e3181d5792a
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.-Y. R., Karydas, A., Seeley, W. W., Josephs, K. A., Coppola, G., Geschwind, D. H., … Rademakers, R. (2011). Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS. Neuron, 72(2), 245–256. https://doi.org/10.1016/j.neuron.2011.09.011
Ducharme, F., Kergoat, M.-J., Antoine, P., Pasquier, F., & Coulombe, R. (2014). Caring for Individuals with Early-Onset Dementia and Their Family Caregivers: The Perspective of Health Care Professionals. Advances in Alzheimer’s Disease, 03(01), 33–43. https://doi.org/10.4236/aad.2014.31005
Duits, F. H., Martinez‐Lage, P., Paquet, C., Engelborghs, S., Lleó, A., Hausner, L., Molinuevo, J. L., Stomrud, E., Farotti, L., Ramakers, I. H. G. B., Tsolaki, M., Skarsgård, C., Åstrand, R., Wallin, A., Vyhnalek, M., Holmber‐Clausen, M., Forlenza, O. V., Ghezzi, L., Ingelsson, M., … Blennow, K. (2016). Performance and complications of lumbar puncture in memory clinics: Results of the multicenter lumbar puncture feasibility study. Alzheimer’s & Dementia, 12(2), 154–163. https://doi.org/10.1016/j.jalz.2015.08.003
Engelborghs, S., Niemantsverdriet, E., Struyfs, H., Blennow, K., Brouns, R., Comabella, M., Dujmovic, I., Van Der Flier, W., Frölich, L., Galimberti, D., Gnanapavan, S., Hemmer, B., Hoff, E., Hort, J., Iacobaeus, E., Ingelsson, M., Jan De Jong, F., Jonsson, M., Khalil, M., … Teunissen, C. E. (2017). Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 8(1), 111–126. https://doi.org/10.1016/j.dadm.2017.04.007
Ferreira, D., Nordberg, A., & Westman, E. (2020). Biological subtypes of Alzheimer disease: A systematic review and meta-analysis. Neurology, 94(10), 436–448. https://doi.org/10.1212/WNL.0000000000009058
Forbes, D., Thiessen, E. J., Blake, C. M., Forbes, S. C., & Forbes, S. (2013). Exercise programs for people with dementia. In The Cochrane Collaboration (Ed.), Cochrane Database of Systematic Reviews (p. CD006489.pub3). John Wiley & Sons, Ltd. https://doi.org/10.1002/14651858.CD006489.pub3
Gass, J., Cannon, A., Mackenzie, I. R., Boeve, B., Baker, M., Adamson, J., Crook, R., Melquist, S., Kuntz, K., Petersen, R., Josephs, K., Pickering-Brown, S. M., Graff-Radford, N., Uitti, R., Dickson, D., Wszolek, Z., Gonzalez, J., Beach, T. G., Bigio, E., … Rademakers, R. (2006). Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Human Molecular Genetics, 15(20), 2988–3001. https://doi.org/10.1093/hmg/ddl241
Goldman, J. S., Hahn, S. E., Catania, J. W., Larusse-Eckert, S., Butson, M. Barber., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., & Bird, T. (2011). Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genetics in Medicine, 13(6), 597–605. https://doi.org/10.1097/GIM.0b013e31821d69b8
Graus, F., Titulaer, M. J., Balu, R., Benseler, S., Bien, C. G., Cellucci, T., Cortese, I., Dale, R. C., Gelfand, J. M., Geschwind, M., Glaser, C. A., Honnorat, J., Höftberger, R., Iizuka, T., Irani, S. R., Lancaster, E., Leypoldt, F., Prüss, H., Rae-Grant, A., … Dalmau, J. (2016). A clinical approach to diagnosis of autoimmune encephalitis. The Lancet Neurology, 15(4), 391–404. https://doi.org/10.1016/S1474-4422(15)00401-9
Harper, L., Barkhof, F., Scheltens, P., Schott, J. M., & Fox, N. C. (2014). An algorithmic approach to structural imaging in dementia. Journal of Neurology, Neurosurgery & Psychiatry, 85(6), 692–698. https://doi.org/10.1136/jnnp-2013-306285
He, Q., Wang, W., Zhang, Y., Xiong, Y., Tao, C., Ma, L., You, C., Ma, J., & Jiang, Y. (2025). Global burden of young-onset dementia, from 1990 to 2021: An age-period-cohort analysis from the global burden of disease study 2021. Translational Psychiatry, 15(1), 56. https://doi.org/10.1038/s41398-025-03275-w
Hsieh, S., Schubert, S., Hoon, C., Mioshi, E., & Hodges, J. R. (2013). Validation of the Addenbrooke’s Cognitive Examination III in Frontotemporal Dementia and Alzheimer’s Disease. Dementia and Geriatric Cognitive Disorders, 36(3–4), 242–250. https://doi.org/10.1159/000351671
Huey, E. D., Putnam, K. T., & Grafman, J. (2006). A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology, 66(1), 17–22. https://doi.org/10.1212/01.wnl.0000191304.55196.4d
Johnson, K. A., Minoshima, S., Bohnen, N. I., Donohoe, K. J., Foster, N. L., Herscovitch, P., Karlawish, J. H., Rowe, C. C., Carrillo, M. C., Hartley, D. M., Hedrick, S., Pappas, V., & Thies, W. H. (2013). Appropriate Use Criteria for Amyloid PET: A Report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association. Journal of Nuclear Medicine, 54(3), 476–490. https://doi.org/10.2967/jnumed.113.120618
Kelley, B. J., Boeve, B. F., & Josephs, K. A. (2008). Young-Onset Dementia: Demographic and Etiologic Characteristics of 235 Patients. Archives of Neurology, 65(11), 1502. https://doi.org/10.1001/archneur.65.11.1502
Kelley, B. J., Boeve, B. F., & Josephs, K. A. (2009). Rapidly Progressive Young-Onset Dementia. Cognitive and Behavioral Neurology, 22(1), 22–27. https://doi.org/10.1097/WNN.0b013e318192cc8d
Koene, S., Rodenburg, R. J., Van Der Knaap, M. S., Willemsen, M. A. A. P., Sperl, W., Laugel, V., Ostergaard, E., Tarnopolsky, M., Martin, M. A., Nesbitt, V., Fletcher, J., Edvardson, S., Procaccio, V., Slama, A., Den Van Heuvel, L. P. W. J., & Smeitink, J. A. M. (2012). Natural disease course and genotype‐phenotype correlations in Complex I deficiency caused by nuclear gene defects: What we learned from 130 cases. Journal of Inherited Metabolic Disease, 35(5), 737–747. https://doi.org/10.1007/s10545-012-9492-z
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013). Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nature Reviews Neurology, 9(2), 106–118. https://doi.org/10.1038/nrneurol.2012.263
Loi, S. M., Cations, M., & Velakoulis, D. (2023). Young‐onset dementia diagnosis, management and care: A narrative review. Medical Journal of Australia, 218(4), 182–189. https://doi.org/10.5694/mja2.51849
McGrowder, D. A., Miller, F., Vaz, K., Nwokocha, C., Wilson-Clarke, C., Anderson-Cross, M., Brown, J., Anderson-Jackson, L., Williams, L., Latore, L., Thompson, R., & Alexander-Lindo, R. (2021). Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives. Brain Sciences, 11(2), 215. https://doi.org/10.3390/brainsci11020215
McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J.-P., Weintraub, D., Aarsland, D., Galvin, J., Attems, J., Ballard, C. G., Bayston, A., Beach, T. G., Blanc, F., Bohnen, N., Bonanni, L., Bras, J., Brundin, P., Burn, D., Chen-Plotkin, A., … Kosaka, K. (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89(1), 88–100. https://doi.org/10.1212/WNL.0000000000004058
Mendez, M. F. (2006). The Accurate Diagnosis of Early-Onset Dementia. The International Journal of Psychiatry in Medicine, 36(4), 401–412. https://doi.org/10.2190/Q6J4-R143-P630-KW41
Papageorgiou, S. G., Kontaxis, T., Bonakis, A., Kalfakis, N., & Vassilopoulos, D. (2009). Frequency and Causes of Early-onset Dementia in a Tertiary Referral Center in Athens. Alzheimer Disease & Associated Disorders, 23(4), 347–351. https://doi.org/10.1097/WAD.0b013e31819e6b28
Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S., & Möbius, H. J. (2003). Memantine in Moderate-to-Severe Alzheimer’s Disease. New England Journal of Medicine, 348(14), 1333–1341. https://doi.org/10.1056/NEJMoa013128
Roach, P., & Keady, J. (2008). Younger people with dementia: Time for fair play. British Journal of Nursing, 17(11), 690–690. https://doi.org/10.12968/bjon.2008.17.11.29604
Rohrer, J. D., Guerreiro, R., Vandrovcova, J., Uphill, J., Reiman, D., Beck, J., Isaacs, A. M., Authier, A., Ferrari, R., Fox, N. C., Mackenzie, I. R. A., Warren, J. D., De Silva, R., Holton, J., Revesz, T., Hardy, J., Mead, S., & Rossor, M. N. (2009). The heritability and genetics of frontotemporal lobar degeneration. Neurology, 73(18), 1451–1456. https://doi.org/10.1212/WNL.0b013e3181bf997a
Rossor, M. N., Fox, N. C., Mummery, C. J., Schott, J. M., & Warren, J. D. (2010). The diagnosis of young-onset dementia. The Lancet Neurology, 9(8), 793–806. https://doi.org/10.1016/S1474-4422(10)70159-9
Ryman, D. C., Acosta-Baena, N., Aisen, P. S., Bird, T., Danek, A., Fox, N. C., Goate, A., Frommelt, P., Ghetti, B., Langbaum, J. B. S., Lopera, F., Martins, R., Masters, C. L., Mayeux, R. P., McDade, E., Moreno, S., Reiman, E. M., Ringman, J. M., Salloway, S., … And the Dominantly Inherited Alzheimer Network. (2014). Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis. Neurology, 83(3), 253–260. https://doi.org/10.1212/WNL.0000000000000596
Sims, R., Hill, M., & Williams, J. (2020). The multiplex model of the genetics of Alzheimer’s disease. Nature Neuroscience, 23(3), 311–322. https://doi.org/10.1038/s41593-020-0599-5
Spector, A., Thorgrimsen, L., Woods, B., Royan, L., Davies, S., Butterworth, M., & Orrell, M. (2003). Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: Randomised controlled trial. British Journal of Psychiatry, 183(3), 248–254. https://doi.org/10.1192/bjp.183.3.248
Van Vliet, D., De Vugt, M. E., Bakker, C., Koopmans, R. T. C. M., Pijnenburg, Y. A. L., Vernooij-Dassen, M. J. F. J., & Verhey, F. R. J. (2011). Caregivers’ perspectives on the pre-diagnostic period in early onset dementia: A long and winding road. International Psychogeriatrics, 23(9), 1393–1404. https://doi.org/10.1017/S1041610211001013
Van Vliet, D., De Vugt, M. E., Bakker, C., Pijnenburg, Y. A. L., Vernooij-Dassen, M. J. F. J., Koopmans, R. T. C. M., & Verhey, F. R. J. (2013). Time to diagnosis in young-onset dementia as compared with late-onset dementia. Psychological Medicine, 43(2), 423–432. https://doi.org/10.1017/S0033291712001122
Vieira, R. T. (2013). Epidemiology of early-onset dementia: A review of the literature. Clinical Practice & Epidemiology in Mental Health, 9(1), 88–95. https://doi.org/10.2174/1745017901309010088
Villemagne, V. L., Fodero-Tavoletti, M. T., Masters, C. L., & Rowe, C. C. (2015). Tau imaging: Early progress and future directions. The Lancet Neurology, 14(1), 114–124. https://doi.org/10.1016/S1474-4422(14)70252-2
Warren, J. D., Rohrer, J. D., & Rossor, M. N. (2013). Frontotemporal dementia. BMJ, 347(aug12 3), f4827–f4827. https://doi.org/10.1136/bmj.f4827
Whitwell, J. L., & Jack, C. R. (2007). Neuroimaging in Dementia. PET Clinics, 2(1), 15–24. https://doi.org/10.1016/j.cpet.2007.09.002
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Copyright (c) 2026 Natalia Surosz, Andrzej Myrny, Kamil Turlej, Dmytro Kowalczuk, Wiktoria Kasianik, Darya Lazitskaya, Mykola Sobchynskyi, Valeryia Milasheuskaya, Iga Kiełbaszewska, Katsiaryna Miraniuk, Dawid Wiczkowski
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