Young-Onset Dementia

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Archives of neurology (Impact Factor: 7.42). 11/2008; 65(11):1502-8. DOI: 10.1001/archneur.65.11.1502
Source: PubMed


Onset of dementia before age 45 years presents a difficult clinical circumstance, having a broad differential diagnosis and numerous psychosocial implications for the patient and their family. Few data exist regarding the demographics characterizing this population or the etiologic diagnoses among those affected.
To characterize the demographic characteristics and the etiologic causes of dementia with age at onset younger than 45 years.
Observational, retrospective, single-cohort study.
Multispecialty group academic medical center.
We searched the Mayo Clinic Rochester electronic Medical Record Linkage System to identify individuals who were seen for evaluation of progressive cognitive decline between the ages of 17 and 45 years from January 1996 through December 2006. This search identified 235 individuals who met the established inclusion and exclusion criteria.
All available clinical, laboratory, magnetic resonance imaging, and pathological data were reviewed.
Causes varied, with neurodegenerative etiologies accounting for 31.1% of the cohort; Alzheimer disease was uncommon. Autoimmune or inflammatory causes accounted for 21.3%. At last follow-up, 44 patients (18.7%) had an unknown etiology, despite exhaustive evaluation. Cause varied with age, with inborn errors of metabolism being more common before age 30 years and with neurodegenerative etiologies being more common after age 35 years.
Young-onset dementia (age at onset, <45 years) includes a broad variety of etiologies, with few patients having a potentially treatable disorder. The etiologic spectrum and the relative percentages of patients within etiologic groups differed in important ways from existing reports of early-onset dementia (ie, age at onset, <65 years).

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    • "Scores of disease processes may ultimately lead to dementia, but there are four major primary disorders with dementia as their main clinical feature: Alzheimer's disease (AD), frontotemporal lobe degeneration (FTLD), cerebrovascular disease, and dementia with Lewy bodies [1] [2]. Diagnosis of the disease ISSN 1387-2877/15/$35.00 "
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    ABSTRACT: Early onset dementias have variable clinical presentations and are often difficult to diagnose. We established a family pedigree that demonstrated consistent recurrence of very early onset dementia in successive generations. In order to refine the diagnosis in this family, we sequenced the exomes of two affected family members and relied on discrete filtering to identify disease genes and the corresponding causal variants. Among the 720 nonsynonymous SNPs shared by two affected members, we found a C to T transition that gives rise to a Thr147Ile missense substitution in the PS1 protein. The presence of this same mutation in a French early-onset Alzheimer's disease family, other affected members of the family, and the predicted high pathogenicity of the substitution strongly suggest that it is the causal variant. In addition to exceptionally young age of onset, we also observed significant limb spasticity and early loss of speech, concurrent with progression of dementia in affected family members. These findings extend the clinical presentation associated with the Thr147Ile variant. Lastly, one member with the Thr147Ile variant was treated with the PKC epsilon activator, bryostatin, in a compassionate use trial after successful FDA review. Initial improvements with this treatment were unexpectedly clear, including return of some speech, increased attentional focus, ability to swallow, and some apparent decrease in limb spasticity. Our findings confirm the role of the PS1 Thr147Ile substitution in Alzheimer's disease and expand the clinical phenotype to include expressive aphasia and very early onset of dementia.
    Full-text · Article · Mar 2015 · Journal of Alzheimer's disease: JAD
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    • "These rules of thumb may assist in screening for the appropriate genes and biochemical testing. Although these metabolic genetic diseases are relatively rare, their prevalence is higher in those under the age of 35 and therefore appropriate genetic testing and biochemical screening should be conducted based on the clinical presentation in affected individuals under this age (Table 1) [4]. Accurate diagnosis will allow proper genetic counseling and provide prognostic guidance to the family, which is an integral component in the management of dementia. "
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    ABSTRACT: This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect.
    Full-text · Article · Jul 2013 · Alzheimer's Research and Therapy
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    • "Les « syndrome démentiels plus » qui associent un syndrome démentiel et des signes de focalisation neurologiques et/ou systémiques peuvent correspondre à des pathologies neurodégénératives ou métaboliques (Tableaux I et II), le plus souvent héréditaires de type autosomique récessif (Rossor et al., 2010). Parmi les pathologies métaboliques, les anomalies de la chaîne respiratoire par mutation de l'ADN mitochondrial ou nucléaire représenteraient environ la moitié des causes de démence de l'adulte avant 45 ans (Kelley et al., 2008). Elles associent souvent d'autres signes neurologiques ou systémiques comme dans les syndromes de MELAS (myopathie, pseudo-accidents vasculaires cérébraux), MERFF (épilepsie myoclonique), MNGIE (signes digestifs et ophtalmoplégie progressive), et NARP (neuropathie, ataxie, rétinite pigmentaire). "
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    ABSTRACT: In the international literature, early onset dementia are defined by the first signs before the age of 65. In France, the Alzheimer plan determined the threshold to 60 years, which is the age for access to certain welfare benefits or accommodation facilities. Today, the number of patients in France with a dementia before the age of 65 is estimated to 32,000 as reported by the Office Parlementaire d’Évaluation des Politiques de Santé (OPEPS) report in 2005. The prevalence of dementia before the age of 65 in population studies is 80 over 100 000 on average. The causes are more numerous and the clinical presentations are more atypical compared to dementia in the elderly, including Alzheimer's disease with a predominance of instrumental difficulties. More the age of onset is earlier, more genetic and metabolic causes, potentially treatable, are common. They are expressed most often by a “dementia plus syndrome”, requiring a detailed clinical evaluation. On the medico-social, aid granted to young patients are specific and include the Prestation de Compensation du Handicap (PCH), which can be obtained from the Maison Départementale des Personnes Handicapées (MDPH), a reference to the administrative procedures of young patients with dementia.
    Full-text · Article · Sep 2012 · Pratique Neurologique - FMC
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