Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Early-onset dementia in adults

Jared R Brosch, MD, MSc
Martin R Farlow, MD
Section Editor
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor
April F Eichler, MD, MPH


Diagnosis and treatment of progressive cognitive impairment in the younger adult requires a different approach than that of the older adult. In particular, the differential diagnosis is much broader and often requires a more extensive evaluation that includes consideration of both common and rare disorders. Nevertheless, the most common causes of early-onset dementia are the same in younger and older adults: Alzheimer disease, vascular dementia, and frontotemporal dementia.

The epidemiology, etiology, evaluation, and diagnosis of early-onset dementia will be reviewed here. A more general approach to adults with cognitive impairment or dementia and disease-specific diagnosis and management are presented elsewhere. (See "Evaluation of cognitive impairment and dementia" and "Treatment of dementia".)


Dementia — Several definitions for dementia exist, but a commonly used framework is one provided by the Diagnostic and Statistical Manual (DSM). According the DSM-5, dementia is defined as significant acquired cognitive impairment in one or more cognitive domains (eg, learning and memory, language, executive function, complex attention, perceptual-motor function, social cognition) that represents a significant decline from previous baseline and interferes with independence in daily activities (table 1) [1]. (See "Evaluation of cognitive impairment and dementia", section on 'Definition of dementia'.)

While this definition recognizes multiple different cognitive domains, a decline in memory is one of the earliest and most prominent features of Alzheimer disease dementia and most other forms of dementia. A prominent exception is frontotemporal dementia, in which memory may be relatively preserved in relation to other cognitive domains such as language function or social cognition, at least initially. For most forms of dementia, however, memory and language dysfunction are generally always present.

Early-onset dementia — Although terminology varies, we consider early-onset dementia (EOD) to refer to cases of dementia occurring in adults ranging from 18 to 65 years of age. Some authors further subdivide EOD, using young-onset dementia to refer to cases with an age of onset between 18 and 45 years. This distinction is somewhat arbitrary, however, and most of the causative diseases do not follow such strict age cut-offs. A common approach to differential diagnosis, including consideration of rare diseases, should be followed regardless of the age of the younger adult with new cognitive change.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jun 6, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.
  2. Harvey RJ, Skelton-Robinson M, Rossor MN. The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry 2003; 74:1206.
  3. Kelley BJ, Boeve BF, Josephs KA. Young-onset dementia: demographic and etiologic characteristics of 235 patients. Arch Neurol 2008; 65:1502.
  4. Ikejima C, Yasuno F, Mizukami K, et al. Prevalence and causes of early-onset dementia in Japan: a population-based study. Stroke 2009; 40:2709.
  5. Borroni B, Alberici A, Grassi M, et al. Prevalence and demographic features of early-onset neurodegenerative dementia in Brescia County, Italy. Alzheimer Dis Assoc Disord 2011; 25:341.
  6. Nordström P, Nordström A, Eriksson M, et al. Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study. JAMA Intern Med 2013; 173:1612.
  7. Shinagawa S, Ikeda M, Toyota Y, et al. Frequency and clinical characteristics of early-onset dementia in consecutive patients in a memory clinic. Dement Geriatr Cogn Disord 2007; 24:42.
  8. Heath CA, Mercer SW, Guthrie B. Vascular comorbidities in younger people with dementia: a cross-sectional population-based study of 616 245 middle-aged people in Scotland. J Neurol Neurosurg Psychiatry 2015; 86:959.
  9. Cations M, Withall A, Low LF, Draper B. What is the role of modifiable environmental and lifestyle risk factors in young onset dementia? Eur J Epidemiol 2016; 31:107.
  10. Knopman DS, Petersen RC, Edland SD, et al. The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994. Neurology 2004; 62:506.
  11. Ryman DC, Acosta-Baena N, Aisen PS, et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 2014; 83:253.
  12. Larner AJ, Doran M. Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene. J Neurol 2006; 253:139.
  13. Bras J, Guerreiro R, Ribeiro M, et al. Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2. BMC Neurol 2008; 8:1.
  14. Caselli RJ, Dueck AC, Osborne D, et al. Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. N Engl J Med 2009; 361:255.
  15. Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 80:496.
  16. Hobson P, Meara J. Risk and incidence of dementia in a cohort of older subjects with Parkinson's disease in the United Kingdom. Mov Disord 2004; 19:1043.
  17. Brockmann K, Srulijes K, Hauser AK, et al. GBA-associated PD presents with nonmotor characteristics. Neurology 2011; 77:276.
  18. Jang YK, Kwon H, Kim YJ, et al. Early- vs late-onset subcortical vascular cognitive impairment. Neurology 2016; 86:527.
  19. Chabriat H, Joutel A, Dichgans M, et al. Cadasil. Lancet Neurol 2009; 8:643.
  20. Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol 2007; 62:442.
  21. Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus vasculopathies: diverse clinical manifestations, laboratory features, pathogenesis, and treatment. Lancet Neurol 2009; 8:731.
  22. Takada LT, Geschwind MD. Prion diseases. Semin Neurol 2013; 33:348.
  23. Ladogana A, Puopolo M, Croes EA, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology 2005; 64:1586.
  24. Heath CA, Cooper SA, Murray K, et al. Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK. J Neurol Neurosurg Psychiatry 2011; 82:646.
  25. Heaton RK, Clifford DB, Franklin DR Jr, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 2010; 75:2087.
  26. Manji H, Jäger HR, Winston A. HIV, dementia and antiretroviral drugs: 30 years of an epidemic. J Neurol Neurosurg Psychiatry 2013; 84:1126.
  27. Rao SM. Neuropsychology of multiple sclerosis. Curr Opin Neurol 1995; 8:216.
  28. Staff NP, Lucchinetti CF, Keegan BM. Multiple sclerosis with predominant, severe cognitive impairment. Arch Neurol 2009; 66:1139.
  29. Calabrese M, Agosta F, Rinaldi F, et al. Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis. Arch Neurol 2009; 66:1144.
  30. Bagert B, Camplair P, Bourdette D. Cognitive dysfunction in multiple sclerosis: natural history, pathophysiology and management. CNS Drugs 2002; 16:445.
  31. Lawn ND, Westmoreland BF, Kiely MJ, et al. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc 2003; 78:1363.
  32. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000; 123 ( Pt 7):1481.
  33. Flanagan EP, Caselli RJ. Autoimmune encephalopathy. Semin Neurol 2011; 31:144.
  34. Flanagan EP, McKeon A, Lennon VA, et al. Autoimmune dementia: clinical course and predictors of immunotherapy response. Mayo Clin Proc 2010; 85:881.
  35. McFarland R, Taylor RW, Turnbull DM. A neurological perspective on mitochondrial disease. Lancet Neurol 2010; 9:829.
  36. McFarland R, Taylor RW, Turnbull DM. The neurology of mitochondrial DNA disease. Lancet Neurol 2002; 1:343.
  37. Baumann N, Turpin JC. Adult-onset leukodystrophies. J Neurol 2000; 247:751.
  38. Rademakers R, Baker M, Nicholson AM, et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet 2011; 44:200.
  39. Eichler FS, Li J, Guo Y, et al. CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids. Brain 2016; 139:1666.
  40. Ayrignac X, Carra-Dalliere C, Menjot de Champfleur N, et al. Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients. Brain 2015; 138:284.
  41. Ahmed RM, Murphy E, Davagnanam I, et al. A practical approach to diagnosing adult onset leukodystrophies. J Neurol Neurosurg Psychiatry 2014; 85:770.
  42. Arsov T, Smith KR, Damiano J, et al. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. Am J Hum Genet 2011; 88:566.
  43. Panegyres PK, Frencham K. Course and causes of suspected dementia in young adults: a longitudinal study. Am J Alzheimers Dis Other Demen 2007; 22:48.
  44. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001; 56:1143.
  45. Rossor MN, Fox NC, Mummery CJ, et al. The diagnosis of young-onset dementia. Lancet Neurol 2010; 9:793.
  46. Waldemar G, Dubois B, Emre M, et al. Diagnosis and management of Alzheimer's disease and other disorders associated with dementia. The role of neurologists in Europe. European Federation of Neurological Societies. Eur J Neurol 2000; 7:133.
  47. Johnson KA, Minoshima S, Bohnen NI, et al. 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. J Nucl Med 2013; 54:476.
  48. Swan A, Waddell B, Holloway G, et al. The diagnostic utility of 99mTc-HMPAO SPECT imaging: a retrospective case series from a tertiary referral early-onset cognitive disorders clinic. Dement Geriatr Cogn Disord 2015; 39:186.
  49. Field M, Witham TF, Flickinger JC, et al. Comprehensive assessment of hemorrhage risks and outcomes after stereotactic brain biopsy. J Neurosurg 2001; 94:545.
  50. McGirt MJ, Woodworth GF, Coon AL, et al. Independent predictors of morbidity after image-guided stereotactic brain biopsy: a risk assessment of 270 cases. J Neurosurg 2005; 102:897.