Early-onset dementias: diagnostic and etiological considerations

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.

Young onset dementia

“…Although Alzheimer disease (AD) is the most common type of dementia in YOD, the proportion due to AD is lower in YOD (15–40%) when compared with LOD (50–70%) . However, in people under the age of 45, there are few AD cases, and most of these are due to autosomal dominant Familial AD . Of the other degenerative dementias, frontotemporal dementia (FTD) and Huntington disease are more prominent in younger people, while dementia with Lewy bodies and Parkinson dementia are perhaps less common.…”

“…In part, due to the different profile of dementia types in YOD, clinical presentations are more varied than in LOD. While subjective and objective memory complaints are a prominent feature, other common presentations include depression, behaviour change and physical symptoms (such as gait disorder, seizures, peripheral neuropathy, visual impairment) in ‘dementia plus’ syndromes …”

“…Another factor that contributes to frustration is that although a dementia diagnosis might be provided or suggested as being highly likely, there may be uncertainty about the type of dementia. Early referral to a memory clinic is perhaps the best option, an approach recommended in Canada, in order to minimise diagnostic delay. Where memory clinics are not easily accessible, referral to a specialist with a known interest in dementia is recommended.…”

“…YOD is a relatively new term that has replaced ‘pre‐senile dementia’; early onset dementia, another term used, has also lost favour as it can be mistaken to mean early or mild dementia. YOD is defined as dementia with symptom onset before the age of 65, an age cut‐off chosen for psychosocial rather than neurobiological reasons . It has been estimated that around 8% of people with dementia in Australia are aged under 65, with the only published Australian data on the prevalence of YOD reporting a rate of 68.2/100 000 in persons aged 30–64 years in south east Sydney .…”

The Diagnostic Utility of ^99mTc-HMPAO SPECT Imaging: A Retrospective Case Series from a Tertiary Referral Early-Onset Cognitive Disorders Clinic

“…There is substantial heterogeneity in the clinical presentation and imaging findings between dementia subtypes [5]. Furthermore, individuals with early-onset AD often present atypically with progressive deficits in visuospatial function or language, often more marked than typical amnestic presentations seen in older adults [6]. …”