Young‐onset dementia (YOD) refers to any dementia where symptom onset occurs at less than 65 years of age1 and is distinct from childhood dementia, which is often diagnosed at 14 years of age or less.2 YOD accounts for about 5% of all dementias, with an estimated prevalence of 119 per 100 000.3 In Australia, about 28 000 people are living with YOD,4 with major associated personal, psychosocial and economic costs.5 While the concept of “young‐onset dementia” has been used since the 1990s, it is only in the past decade that there has been increasing recognition that the diagnostic and post‐diagnostic issues in YOD are distinct from those occurring in older people. People with YOD contend with delays to diagnosis and difficulty navigating the complex health, aged and disability care systems, while often also caring for or supporting children or young people. Improved access to assessment, timely diagnosis, and appropriate post‐diagnosis care can have important benefits for improving function and quality of life. In this narrative review, we present a clinical approach to YOD, reporting on advances in diagnosis, management, and access to care. Using our collective knowledge of YOD, combined with a PubMed search of “young‐onset dementia” and “younger‐onset dementia”, we included publications from 2002 to 2022, prioritising those from an Australian setting. We included what we considered seminal papers in the area and excluded childhood dementia and secondary causes of dementia.
Aetiology and diagnosis
As for dementias with an older onset, Alzheimer disease (AD), frontotemporal dementias (FTD)6,7 and vascular dementias8,9 are the most frequent causes of YOD. However, the aetiological profile of YOD is more diverse than in later life and is more likely to be caused by a rarer pathology or occur secondarily to another condition. In particular, alcohol‐related dementias10 usually have an onset in midlife. YOD can also occur secondarily to other causes, including neurological (eg, Huntington disease, Parkinson disease, multiple sclerosis, traumatic brain injury, motor neuron disease), infective (eg, neurosyphilis, human immunodeficiency virus) and other (eg, systemic lupus erythematosus, alcohol‐related).1 People with intellectual disability are recognised as having increased risk for developing dementia,11 and most people with Down syndrome will exhibit symptoms consistent with AD by 65 years of age.12 For Indigenous Australians, the prevalence of dementia is reported as 12.4%. This is five times greater than the Australian population rate (2.4%), with a much earlier onset of illness.13 The most common cause of dementia in an Indigenous Australian population was reported as dementia not otherwise specified (53%) and Alzheimer type (24%).13
The presenting symptoms of YOD are more variable than the initial symptoms seen in older adults. In younger people, early presenting symptoms often include behaviour, language and personality change, and executive dysfunction (Box 1). In young‐onset AD, there are several variants: (i) posterior cortical atrophy presenting with visual problems (ocular motor apraxia, simultanagnosia), apraxias and Gertsmann syndrome (acalculia, finger agnosia, agraphia, left–right disorientation); (ii) frontal variant AD or behavioural/executive AD, presenting with symptoms similar to behavioural variant FTD (bv‐FTD);14 and (iii) logopaenic variant primary progressive aphasia, presenting with language difficulties such as word‐finding difficulties and decreased repetition of sentences.15 FTD often presents with impulsive or inappropriate behaviour, executive problems, and language impairments.16 The most common genetic cause of FTD, the GGGGCC hexanucleotide repeat mutation in C9orf72,17 can present with symptoms consistent with a bv‐FTD or motor neuron disease (or both), as well as psychiatric symptoms that may predate cognitive symptoms by up to two decades.18
This variability highlights the difficulty with timely and accurate diagnosis resulting in diagnostic delay of three to five years.22,23 This is longer than time to diagnosis in older‐onset dementia.24 An accurate diagnosis of dementia early in the disease process is critically important for younger people as there are significant implications for management, access to support services, prognosis, and future planning. Guidelines recommend consideration of the possibility of YOD in a middle‐aged individual who presents with reasonably new onset psychiatric symptoms with no previous psychiatric history.25 Other reasons for referral for further investigation and assessment are listed in Box 2.
International consensus on guidelines for assessment in YOD is listed in Box 3.25 Due to the potential reversibility of secondary YODs, it is important to perform a thorough screen for reversible causes (Box 4). The Mini‐Mental State Examination (MMSE)26 may be within normal limits for an individual with a YOD such as bv‐FTD,27 and an alternative screening cognitive examination (such as Addenbrooke's Cognitive Examination III Revised28 or Neuropsychiatry Unit Cognitive Screening [NUCOG] tool29) should be considered. Identification of dementia in people with Down syndrome and other intellectual disabilities can be difficult without premorbid cognitive assessment data. Neuropsychological assessment of a person with intellectual disability in early adulthood can be useful for detecting cognitive decline,30 and mid‐ to late‐life behaviour changes reported by family and carers can be important early signs of neurodegeneration.31 For Indigenous Australians, the Kimberley Indigenous Cognitive Assessment is a reliable cognitive assessment tool for detecting cognitive impairment and can be used in rural and remote areas such as in the Kimberley, Northern Queensland and the Pilbara.32
Imaging
Brain neuroimaging, including structural and functional scans, forms part of a comprehensive assessment for YOD.25 A magnetic resonance imaging (MRI) brain scan may detect atrophy in regional areas indicative of a dementia syndrome. For example, hippocampal atrophy is seen in AD and frontotemporal atrophy in FTD. Radiological visual rating scales can be a quick, relatively accessible and practical way of improving diagnostic accuracy, although this may depend on clinical experience,33 and automated normative morphometry, if available, may improve detection of regional atrophy regardless of radiological experience.34 A neurodegenerative protocol for brain MRI would ideally include the three main planes (sagittal, coronal and axial) and include T1, T2, fluid‐attenuated inversion recovery and diffusion weighted imaging sequences in each. Functional imaging such as fluorodeoxyglucose positron emission tomography (FDG‐PET) or single‐photon emission computed tomography scans, less accurate than FDG‐PET, can identify dementia‐related changes by quantitatively demonstrating cerebral glucose hypometabolism and decreased brain activity, respectively.35 Box 5 summarises common neuroimaging changes in various dementias.
New molecular neuroimaging research technologies can provide a non‐invasive method of improved diagnostic accuracy. Amyloid‐β (Aβ) imaging can selectively identify the Aβ‐containing plaques that are the hallmark pathological feature of AD.36 Several compounds are available to accurately distinguish AD from age‐matched controls and can assist in the distinction between different types of dementia such as AD and FTD.37 The degree of amyloid accumulation on Aβ imaging may not correlate with severity of cognitive impairment, as the accumulation of amyloid likely reaches a threshold.37 A negative Aβ PET scan in a person with cognitive symptoms is helpful for differential diagnosis, because it excludes the presence of amyloid as a cause of these symptoms and can exclude AD. Tau PET scans have become useful in identifying the tau based neurofibrillary tangles, which are pathological contributors to AD.36 These PET ligands are not specific for AD as they also identify tau accumulation in other tauopathies such as some FTDs, progressive supranuclear palsy, and chronic traumatic encephalopathy.38 Regional distributions of tau can help to guide differential diagnosis.39
To lumbar puncture or not to lumbar puncture?
Analysis of cerebrospinal fluid (CSF) via lumbar puncture is another important tool in the diagnosis of dementia in younger people.25 The CSF can be analysed to determine the quantity of Aβ40 and Aβ42 and total tau (t‐tau) and phosphorylated tau (p‐tau), both indicative of AD. Although a CSF analysis via lumbar puncture may be more invasive than a brain scan, it is potentially more cost‐effective and accessible.40 CSF analysis can rule in AD and identify other neurological disorders that might also cause symptoms of confusion (eg, tumours and infections). There is very strong agreement between the CSF ratios of Aβ40 and Aβ42 with t‐tau and p‐tau with amyloid PET, with negative predictive values of at least 98% and positive predictive values of at least 77%.41 This suggests that CSF analysis for AD proteins has similar correlation in the quantification of amyloid pathology, further supporting the use of lumbar punctures, especially in younger people. The underuse of CSF analysis40 may be due to physician hesitancy in ordering a lumbar puncture, lack of confidence in performing one, perceived risk of side effects, and a perception that there are limited benefits of diagnosing AD given a lack of disease‐modifying treatments.40 In addition, CSF analysis for Alzheimer proteins requires specialised laboratories and standardised procedures, which are not easily accessible all over Australia and currently are not funded by Medicare. Despite this, given the safety, tolerability, patient acceptability and diagnosis that a lumbar puncture can provide, CSF analysis should be part of the assessment process for those suspected of having YOD.25,40
Recent research evidence suggests that neurofilament light chain, a component of the axons that is released into CSF when there is damage (eg, due to neurodegeneration or traumatic brain injury), may have utility in the diagnosis of YOD. Analysis of neurofilament light chain has been found to have 87% sensitivity and 90% specificity in differentiating between primary psychiatric disorders and dementia in younger people,42 and this can also be replicated with plasma biomarkers of neurofilament light chain, p‐tau 181, p‐tau 217, glial fibrillary acidic protein, Aβ40 and Aβ42,43 potentially improving accessibility.
Genetic factors
About 15% of all YOD cases are caused by an autosomal dominant genetic mutation.44 Genetic testing is highly recommended when dementia is diagnosed in a younger person, especially with a family history of YOD,25 onset before 45 years of age, and with a dementia type with a high heritability rate. Directly inherited cases occur in nearly 50% of people with onset before age 45 years.45 FTD is also more likely to be inherited than other dementia types, with autosomal‐dominant inheritance occurring in 20–50% of cases (usually the C9orf72 mutation).46 Other familial types of YOD include Huntington disease, Niemann–Pick disease type C, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy.
Finding a genetic cause of dementia can provide diagnostic certainty and has significant implications for the family of the affected individual. Three types of next generation sequencing techniques are currently available for clinical use: (i) targeted gene panels that only include specific genes for a particular disorder; (ii) whole exome sequencing that can read sequences from all coding regions; and (iii) whole genome sequencing that analyses sequences in coding and non‐coding regions (this may include all genetic causes of dementias and could potentially increase diagnostic accuracy).47,48 There are limitations with this technology in that large duplications and structural variations cannot be read by these techniques, nor can triplicate repeat disorders such as the CAG (cytosine, adenine, guanine) repeat in Huntington disease and disorders related to the C9orf72 mutation.48 In addition, not all genetic variants have clinical significance, and some genetic risk factors, such as the APOE risk allele, have unclear significance. Genetic counselling before testing and receiving results is therefore recommended for discussion of this complex information for families.48
Management
People with YOD usually live for many years after their diagnosis and longer than those with older‐onset dementia.49 The delivery of high quality, integrated and multidisciplinary post‐diagnosis management and care promotes quality of life and community engagement for the benefit of the person and their wider family and community.
Medical management
Medical management in the first years after a YOD diagnosis should include repeat assessments, including neuroimaging and neuropsychology, to characterise the dementia (ie, diagnostic stability, prognosis). Some dementias, such as bv‐FTD, are difficult to diagnose at one timepoint and individuals may perform within normal limits on neuropsychological testing, so are often misdiagnosed with a psychiatric condition, a different dementia,50 or phenocopy syndrome (people presenting with the neuropsychiatric symptoms that mimic bv‐FTD but who may not have frontotemporal atrophy or hypometabolism on neuroimaging, or the progression/deterioration required for a diagnosis of dementia).51 There are recommendations for differentiating bv‐FTD from psychiatric disorders,27 and regardless of the type of YOD, repeated assessments are important to confirm or specify a diagnosis.50
For young‐onset AD, treatment using cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine are indicated but do not modify disease progression.52 Management of cardiovascular risk factors and other lifestyle modification may also slow cognitive decline in people with YOD.53
Medical management is important for addressing the psychiatric symptoms and impacts of YOD. Most people with YOD experience symptom onset at a time of peak financial, familial and occupational responsibility, and their illness commonly causes profound distress. People with YOD regularly report loss of identity and role changes, feelings of hopelessness and powerlessness, and social exclusion.54,55 Recent research has found that people with YOD aged 45 to 64 years are 2.8 times more likely to die by suicide than people without dementia in the same age range.56 Although this likely represents a small number of suicide deaths overall, the risk for death by suicide declines with time from diagnosis. As such, close follow‐up soon after a diagnosis is given is recommended. Treatment for low mood and anxiety should follow general treatment guidelines, including modified psychotherapy and antidepressants with short term benzodiazepines for depression and anxiety.57 Sleep disturbances can be managed by non‐pharmacological management tailored to the individual, and melatonin or short term low dose benzodiazepines may be required.58
Post‐diagnosis care and support
In Australia, most dementia care services are embedded within the aged care system, and as such are designed and tailored for older people living with dementia.59,60 These services can lack suitability for young people with dementia and their families.60 The transferral of funding arrangements for social and allied health care services for YOD to the National Disability Insurance Scheme (NDIS) in 2017 was therefore welcomed by people with YOD and their families. However, recent research suggests that people with YOD and their families continue to have difficulty accessing the NDIS and finding suitable services with which to spend their funding.61
Post‐diagnostic care for younger people with dementia should be tailored, flexible, affordable and provide meaningful engagement.60 An assessment of the specific disabilities experienced by the person will help to guide non‐pharmacological treatment and care. People with YOD may benefit from a multidisciplinary approach including psychology or counselling, functional assessment with home modifications and help with activities of daily living (known as Supported Independent Living within the NDIS), speech pathology, physiotherapy and/or exercise physiology, home support (eg, cleaning, cooking), financial management, and assistance with advance care planning. Advance care planning should begin at the time of diagnosis and include consideration of financial affairs, care and living arrangements, end of life preferences, and eventual driving cessation. Some people with YOD with a shorter life expectancy (eg, motor neuron disease, some FTDs) may consider voluntary assisted dying if this is available in their state. Consideration should be given to the specific eligibility requirements for voluntary assisted dying that differ between states. Social support, particularly with other younger people with rare illness, can promote quality of life.62 Multi‐agency support is often needed to promote the continued employment of younger people with dementia, starting with accommodations and changes in role, before transitioning into early retirement.63
Behaviour management
Neuropsychiatric and behavioural symptoms are important causes of distress for people with YOD64 and their family members,65 and can cause premature entry to residential care.66 These symptoms occur in most individuals with YOD and can be categorised into affective (depression, apathy, anxiety, elation, irritability); psychotic (delusions, hallucinations, paranoia); hyperactivity (pacing, restlessness, disinhibition); aggression/agitation (verbal, physical); and other changes (wandering, intrusiveness, shadowing, reverse sleep–wake cycle, inappropriate behaviours such as urination).66 Complex neuropsychiatric and behavioural symptoms can lead a person with YOD to “bounce” between aged, disability and health services because of a lack of multidisciplinary management skills and services.67 Challenging behaviour and personality change is particularly common among those with frontal‐related dementias such as bv‐FTD, alcohol‐related dementias, and chronic traumatic encephalopathy.68
In some cases, behaviour changes are manifestations of an unmet need that the individual is unable to communicate (eg, temperature regulation, boredom) or a reflection of the person's lowered stress threshold.69 Recommendations for the management of behavioural symptoms endorse non‐pharmacological strategies as a first line approach.70 Assessment of the triggers, features and consequences of a behaviour can help to identify its function for the person and point to potentially effective interventions.69 Psychoeducation and training for family carers about behaviour management can effectively reduce the impact of behaviour change.69
Where pharmacological treatment is required as an adjunct to non‐pharmacological therapies, international guidelines recommend a “start low and go slow” approach to prescribing.71 Benzodiazepines may provide short term benefit for sleep disturbance, agitation and anxiety.57 Pain is a common contributor to behaviour change, and pain management should be considered as a useful addition.72 Risperidone is indicated for short term (maximum 12 weeks) management of severe psychotic symptoms or aggressive behaviour dementia,73,74 but prescribers should consider that all antipsychotic medications are associated with major risks for people with dementia, including stroke and extrapyramidal symptoms.75 There is a black box warning for some antipsychotic medications with risk of sudden death due to cardiac arrythmias, although this has been reported for those over 65 years of age.76 However, obtaining an electrocardiogram before commencement is recommended for those who have dementia and are aged under 65 years. Policy and regulatory efforts to reduce the overuse of antipsychotic medications are underway in many countries.77 Prescribing should also consider that some behaviour changes are less responsive to psychotropic medications, including wandering, vocalisations, shadowing, intrusiveness, repetitive activities, and inappropriate behaviours such as urination/defecation, undressing, and sexualised behaviour.69,78
Family
YOD has a major impact on the family of the person affected. Family carers of people with YOD experience changes to their self‐identity and relationships, and are at high risk for social isolation.54,79 Carer burden is high, particularly for spouses of people with YOD, who are sometimes also caring for children and ageing parents.80,81,82 Children of people with YOD experience disrupted emotional, psychological and social development, and are at high risk for the development of psychological illness.83 A whole‐of‐family approach to the management of YOD is needed to ensure that families have adequate access to financial resources, respite, social and educational opportunities, and psychoeducation.84 Carer and family wellbeing can be promoted via psychological or counselling support, regular respite breaks, NDIS pre‐planning and support coordination, and social support groups such as those offered by Dementia Australia.
Housing
Although younger people with dementia usually prefer to live and die at home, cognitive, functional and behaviour impairments can necessitate long term care. Traditional residential care facilities for older adults may be inappropriate for younger people and the Australian Government has pledged that no one aged under 65 years will enter or live in residential aged care by 2022 and 2025, respectively.85 However, few appropriate long term housing alternatives currently exist for people with YOD, and the establishment of YOD‐specific facilities may be financially untenable, particularly in regions where few people with YOD live. Potential solutions might include supported disability accommodation designed to accommodate cognitive disabilities, and/or hybrid models that capitalise on both the extensive experience in dementia care within the aged care sector and the strengths‐based focus of the disability sector.67
Prognosis
Accurate differential diagnosis of YOD is helpful for estimating progression and prognosis, and the course of YOD will depend on the dementia type, premorbid health, and other factors. Young people with AD experience faster cognitive decline than older people with AD, but research examining the impact of onset age on symptom progression in other dementias is inconclusive.86
Recent research found that the median survival from age of onset for younger people with AD, FTD and vascular dementia was 11.3 years, 10.6 years and 12.3 years, respectively (Loi SM, Tsoukra V, Sun E, et al. Manuscript in preparation). Dementias caused by autosomal‐dominant gene mutations (eg, MAPT‐type FTD) are usually associated with earlier age of onset and age at death,87 and FTD associated with motor neuron disease has the shortest duration of survival.88 Overall, people with YOD lose 10 to 15 years of life expectancy.89
Conclusion
Our understanding of the pathogenesis, aetiological profile, diagnosis and management of YOD has significantly improved over the past decade. We propose several actions to improve the care of people with YOD in Australia (Box 6). Younger people with dementia may live for a decade with the disease and most will remain living in the community, supported by families and community services. Thus, we also propose that a paradigm shift is needed with the concept of “dementia”, in order to decrease stigma and fear associated with this condition. Dementia ought to be considered a chronic disease which progresses over time, but with age‐appropriate interventions and services, we can continue to support and improve the quality of life of people with dementia as they deteriorate. Although there are no disease‐modifying treatments for most types of YOD, timely diagnosis and multidisciplinary care and support can have major benefits for promoting community participation and quality of life for people with YOD and their families.
Box 1 – The aetiology of young‐onset dementia
|
Dementia type |
Initial symptoms |
Genes implicated |
Proteins implicated |
Reference |
|||||||||||
|
|
|||||||||||||||
|
Alzheimer disease |
Short term memory impairment |
APOE |
Amyloid‐β |
McKhann et al19 |
|||||||||||
|
Posterior cortical atrophy |
Apraxias |
|
Amyloid‐β |
|
|||||||||||
|
Behavioural variant FTD |
Behavioural and personality changes |
MAPT |
Tau TAR DNA‐binding protein 43 |
Rascovsky criteria20 |
|||||||||||
|
FTD–MND |
Behavioural changes |
C9orf72 |
TAR DNA‐binding protein 43 |
|
|||||||||||
|
Semantic dementia |
Semantic impairment |
|
Tau |
Gorno‐Tempini et al15 |
|||||||||||
|
Progressive non‐fluent aphasia |
Progressive speech production impairment |
|
Tau |
Gorno‐Tempini et al15 |
|||||||||||
|
Progressive supranuclear palsy |
Falls, gait and balance problems |
|
Tau (four repeats) |
|
|||||||||||
|
Corticobasal syndrome |
Asymmetrical apraxia and rigidity |
|
Tau (four repeats) |
Armstrong et al21 |
|||||||||||
|
|
|||||||||||||||
|
FTD = frontotemporal dementia; MND = motor neuron disease. |
|||||||||||||||
Box 2 – Red flags and factors that may require further assessment for young‐onset dementia
- New onset (ie, in past 10 years rather than development in adolescence or young adulthood) in someone of middle age who has no previous psychiatric history
- Behaviour changes that are not consistent with previous personality
- Progressive neurological symptoms or seizures
- Cognitive/behavioural/psychiatric changes in a person with a family history of young‐onset dementia
- Minimal improvement of psychiatric symptoms following psychotherapy, counselling or psychotropic medications
Box 3 – Guidelines for assessment in young‐onset dementia*
|
Aspect of care |
Recommendations |
||||||||||||||
|
|
|||||||||||||||
|
Pre‐assessment and communication |
Many professionals required over time |
||||||||||||||
|
|
Important to convey the diagnosis to the individual and family and remain open to review and modify this diagnosis |
||||||||||||||
|
|
Important to obtain rapport |
||||||||||||||
|
|
Need to find out what supports are required |
||||||||||||||
|
|
Checking if the individual has capacity |
||||||||||||||
|
History taking |
Collateral history important |
||||||||||||||
|
|
Symptom onset and type |
||||||||||||||
|
|
Frontotemporal dementia symptoms (such as loss of empathy, apathy, behavioural changes) |
||||||||||||||
|
|
Physical health and other medical conditions |
||||||||||||||
|
|
Function: eg, activities of daily living |
||||||||||||||
|
|
Drug and alcohol history |
||||||||||||||
|
Family history |
Obtain a three‐generational history of young‐onset dementia |
||||||||||||||
|
Physical examination |
Including neurological examination |
||||||||||||||
|
Risk assessment |
Occupational risks, driving, other risky behaviour eg, gambling |
||||||||||||||
|
Psychiatric assessment |
Previous psychiatric history and symptoms |
||||||||||||||
|
|
History of learning disability or intellectual disability |
||||||||||||||
|
Neuroimaging |
Magnetic resonance imaging (at the minimum) |
||||||||||||||
|
Neuropsychological assessment |
Screening testing, not just Mini Mental State Examination (eg, ACE‐R or NUCOG) |
||||||||||||||
|
Palliative care |
Support is required from diagnosis to end of life care |
||||||||||||||
|
|
|||||||||||||||
|
ACE‐R = Addenbrooke's Cognitive Examination Revised; NUCOG = Neuropsychiatry Unit Cognitive Screening tool. * Adapted from O'Malley et al.25 |
|||||||||||||||
Box 4 – Potential reversible causes of dementia occurring in a younger person
- Inflammatory: multiple sclerosis, neurosarcoidosis, autoimmune encephalitis
- Infection: human immunodeficiency virus, neurosyphillis, Whipple disease
- Misuse of alcohol or other drugs
- Heavy metal poisoning
- Metabolic and endocrine: thyroid disease, Wilson disease
- Other causes: obstructive sleep apnoea, normal pressure hydrocephalus
Box 5 – Neuroimaging changes in some young‐onset dementias
|
Young‐onset dementia |
Magnetic resonance imaging: areas affected |
Positron emission tomography: areas affected |
Other imaging modalities |
||||||||||||
|
|
|||||||||||||||
|
Alzheimer disease |
Hippocampus |
Precuneus |
Amyloid‐β positron emission tomography |
||||||||||||
|
Posterior cortical atrophy |
Posterior/occipital regions |
Parietooccipital cortices |
Amyloid‐β positron emission tomography |
||||||||||||
|
Behavioural variant frontotemporal dementia |
Frontal (medial, orbitofrontal, anterior insula) |
Frontotemporal |
|
||||||||||||
|
Semantic frontotemporal dementia |
Anterior temporal |
Frontal midline structure (cingulate, orbitofrontal and anterior medial cortices, insula) |
|
||||||||||||
|
Progressive non‐fluent aphasia |
|
Frontotemporal region of left side: inferior frontal region, dorsolateral prefrontal, Broca and Wernicke area, and inferior temporal regions |
|
||||||||||||
|
|
|||||||||||||||
|
|
|||||||||||||||
Box 6 – Actions to improve the care of people living with young‐onset dementia and their families
- Promote pathways of care for timely diagnosis, especially for Indigenous Australians, including integration of the disability, health and aged care sections, and access to telehealth
- Improve diagnostic accuracy
- Improve pathways to research so that people with young‐onset dementia can be included
- Highlight the concept that young‐onset dementia is a condition that causes disability that requires timely access to the National Disability Insurance Scheme (NDIS), and to improve the NDIS workforce in knowledge and care of younger people with dementia
- Promote prompt advanced care planning, consideration of driving cessation, and implementation of accommodations to promote ongoing workforce participation
- Integrate age‐appropriate services for family members of people with young‐onset dementia in existing health care systems
- Enable access to appropriate accommodation and palliative care
Provenance: Commissioned; externally peer reviewed.
- Samantha M Loi1,2
- Monica Cations3
- Dennis Velakoulis1,2
- 1 University of Melbourne, Melbourne, VIC
- 2 Royal Melbourne Hospital, Melbourne, VIC
- 3 Flinders University, Adelaide, SA
Open access
Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians.
Monica Cations is supported by The Hospital Research Foundation Early Career Fellowship (ECF‐2019‐33‐25271) and a Medical Research Future Fund/National Health and Medical Research Council Investigator Grant (GNT 1194084). The funders had no role in the planning, writing or publication of the work.
No relevant disclosures.
- 1. Rossor MN, Fox NC, Mummery CJ, et al. The diagnosis of young‐onset dementia. Lancet Neurol 2010; 9: 793‐806.
- 2. Nunn K, Williams K, Ouvrier R. The Australian Childhood Dementia Study. Eur Child Adolesc Psychiatry 2002; 11: 63‐70.
- 3. Hendriks S, Peetoom K, Bakker C, et al. Global prevalence of young‐onset dementia: a systematic review and meta‐analysis. JAMA Neurol 2021; 78:1080‐1090.
- 4. Dementia Australia. Dementia prevalence data. https://www.dementia.org.au/information/statistics/prevalence‐data (viewed Nov 2022).
- 5. Draper B, Withall A. Young onset dementia. Intern Med J 2016; 46: 779‐786.
- 6. Loi SM, Eratne D, Goh AMY, et al. A 10 year retrospective cohort study of inpatients with younger‐onset dementia. Int J Geriatr Psychiatry 2021; 36: 294‐301.
- 7. Panegyres PK, Frencham K. Course and causes of suspected dementia in young adults: a longitudinal study. Am J Alzheimers Dis Other Demen 2007; 22: 48‐56.
- 8. Ikejima C, Yasuno F, Mizukami K, et al. Prevalence and causes of early‐onset dementia in Japan: a population‐based study. Stroke 2009; 40: 2709‐2714.
- 9. McMurtray A, Clark DG, Christine D, et al. Early‐onset dementia: frequency and causes compared to late‐onset dementia. Dement Geriatr Cogn Disord 2006; 21(2): 59‐64.
- 10. Withall A, Draper B, Seeher K, et al. The prevalence and causes of younger onset dementia in Eastern Sydney, Australia. Int Psychogeriatrics 2014; 26: 1955‐1965.
- 11. Evans E, Bhardwaj A, Brodaty H, et al. Dementia in people with intellectual disability: insights and challenges in epidemiological research with an at‐risk population. Int Rev Psychiatry 2013; 25: 755‐763.
- 12. Lott IT, Head E. Dementia in Down syndrome: unique insights for Alzheimer disease research. Nat Rev Neurol 2019; 15: 135‐147.
- 13. Smith K, Flicker L, Lautenschlager NT, et al. High prevalence of dementia and cognitive impairment in Indigenous Australians. Neurology 2008; 71: 1470‐1473.
- 14. Mendez MF. Early‐onset Alzheimer disease and its variants. Continuum (Minneap Minn) 2019; 25: 34‐51.
- 15. Gorno‐Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76: 1006‐1014.
- 16. Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet 2015; 386: 1672‐1682.
- 17. Ducharme S, Bajestan S, Dickerson BC, et al. Psychiatric presentations of C9orf72 mutation: what are the diagnostic implications for clinicians? J Neuropsychiatry Clin Neurosci 2017; 29: 195‐205.
- 18. Khan BK, Yokoyama JS, Takada LT, et al. Atypical, slowly progressive behavioural variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion. J Neurol Neurosurg Psychiatry 2012; 83: 358‐364.
- 19. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011; 7: 263‐269.
- 20. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011; 134: 2456‐2477.
- 21. Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology 2013; 29; 80: 496‐503.
- 22. Loi SM, Goh AMY, Mocellin R, et al. Time to diagnosis in younger‐onset dementia and the impact of a specialist diagnostic service. Int Psychogeriatr 2022; 34: 367‐375.
- 23. Draper B, Cations M, White F, et al. Time to diagnosis in young‐onset dementia and its determinants: the INSPIRED study. Int J Geriatr Psychiatry 2016; 31: 1217‐1224.
- 24. van Vliet D, de Vugt ME, Bakker C, et al. Time to diagnosis in young‐onset dementia as compared with late‐onset dementia. Psychol Med 2013; 43: 423‐432.
- 25. O'Malley M, Parkes J, Stamou V, et al. International consensus on quality indicators for comprehensive assessment of dementia in young adults using a modified e‐Delphi approach. Int J Geriatr Psychiatry 2020; 35: 1309‐1321.
- 26. Folstein MF, Folstein SE, McHugh PR. “Mini‐mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189‐198.
- 27. Ducharme S, Dols A, Laforce R, et al. Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders. Brain 2020; 143: 1632‐1650.
- 28. Mioshi E, Dawson K, Mitchell J, et al. The Addenbrooke's Cognitive Examination Revised (ACE‐R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 2006; 21: 1078‐1085.
- 29. Walterfang M, Siu R, Velakoulis D. The NUCOG: validity and reliability of a brief cognitive screening tool in neuropsychiatric patients. Aust N Z J Psychiatry 2006; 40: 995‐1002.
- 30. McKenzie K, Metcalfe D, Murray G. A review of measures used in the screening, assessment and diagnosis of dementia in people with an intellectual disability. J Appl Res Intellect Disabil 2018; 31: 725‐742.
- 31. Jamieson‐Craig R, Scior K, Chan T, et al. Reliance on carer reports of early symptoms of dementia among adults with intellectual disabilities. J Policy Pract Intellect Disabil 2010; 7: 34‐41.
- 32. LoGiudice D, Smith K, Thomas J, et al. Kimberley Indigenous Cognitive Assessment tool (KICA): development of a cognitive assessment tool for older indigenous Australians. Int Psychogeriatr 2006; 18: 269‐280.
- 33. Harper L, Fumagalli GG, Barkhof F, et al. MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post‐mortem confirmed cases. Brain 2016; 139: 1211‐1225.
- 34. Wibawa P, Matta G, Das S, et al. Bringing psychiatrists into the picture: Automated measurement of regional MRI brain volume in patients with suspected dementia. Aust N Z J Psychiatry 2021; 55: 799‐808.
- 35. Berti V, Pupi A, Mosconi L. PET/CT in diagnosis of dementia. Ann N Y Acad Sci 2011; 1228: 81‐92.
- 36. DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener 2019; 14: 32.
- 37. Villemagne VL, Barkhof F, Garibotto V, et al. Molecular imaging approaches in dementia. Radiology 2021; 298: 517‐530.
- 38. Zhang Y, Wu KM, Yang L, et al. Tauopathies: new perspectives and challenges. Mol Neurodegener 2022; 17: 28.
- 39. Stern RA, Adler CH, Chen K, et al. Tau positron‐emission tomography in former National Football League players. N Engl J Med 2019; 380: 1716‐1725.
- 40. Hampel H, Shaw LM, Aisen P, et al. State‐of‐the‐art of lumbar puncture and its place in the journey of patients with Alzheimer's disease. Alzheimers Dement 2022; 18: 159‐177.
- 41. Campbell MR, Ashrafzadeh‐Kian S, Petersen RC, et al. P‐tau/Abeta42 and Abeta42/40 ratios in CSF are equally predictive of amyloid PET status. Alzheimers Dement (Amst) 2021; 13: e12190.
- 42. Eratne D, Loi SM, Walia N, et al. A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: a ‘C‐reactive protein’ for psychiatrists and neurologists? Aust N Z J Psychiatry 2020; 54: 57‐67.
- 43. Chouliaras L, Thomas A, Malpetti M, et al. Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 2022; 93: 651‐658.
- 44. Jarmolowicz AI, Chen HY, Panegyres PK. The patterns of inheritance in early‐onset dementia: Alzheimer's disease and frontotemporal dementia. Am J Alzheimers Dis Other Demen 2015; 30: 299‐306.
- 45. Kelley BJ, Boeve BF, Josephs KA. Young‐onset dementia: demographic and etiologic characteristics of 235 patients. Arch Neurol 2008; 65: 1502‐1508.
- 46. Olszewska DA, Lonergan R, Fallon EM, et al. Genetics of frontotemporal dementia. Curr Neurol Neurosci Rep 2016; 16: 107.
- 47. Huq AJ, Thompson B, Bennett MF, et al. Clinical impact of whole‐genome sequencing in patients with early‐onset dementia. J Neurol Neurosurg Psychiatry 2022; 93: 1181‐1189.
- 48. Huq AJ, Sexton A, Lacaze P, et al. Genetic testing in dementia‐A medical genetics perspective. Int J Geriatr Psychiatry 2021; 36: 1158‐1170.
- 49. Loi SM, Tsoukra P, Chen Z, et al. Mortality in dementia is predicted by older age of onset and cognitive presentation. Aust N Z J Psychiatry 2022; 56: 852‐861.
- 50. Tsoukra P, Velakoulis D, Wibawa P, et al. The diagnostic challenge of young‐onset dementia syndromes and primary psychiatric diseases: results from a retrospective 20‐year cross‐sectional study. J Neuropsychiatry Clin Neurosci 2022; 34: 44‐52.
- 51. Devenney E, Forrest SL, Xuereb J, et al. The bvFTD phenocopy syndrome: a clinicopathological report. J Neurol Neurosurg Psychiatry 2016; 87: 1155‐1156.
- 52. Kaduszkiewicz H, Zimmermann T, Beck‐Bornholdt HP, et al. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised trials. BMJ 2005; 331: 321‐327.
- 53. Rosenberg A, Mangialasche F, Ngandu T, et al. Multidomain interventions to prevent cognitive impairment, Alzheimer's disease, and dementia: from FINGER to world‐wide FINGERS. J Prev Alzheimers Dis 2020; 7: 29‐36.
- 54. Nwadiugwu M. Early‐onset dementia: key issues using a relationship‐centred care approach. Postgrad Med J 2021; 97: 598‐604.
- 55. Johannessen A, Engedal K, Haugen PK, et al. “To be, or not to be”: experiencing deterioration among people with young‐onset dementia living alone. Int J Qual Stud Health Well‐being 2018; 13: 1490620.
- 56. Alothman D, Card T, Lewis S, et al. Risk of suicide after dementia diagnosis. JAMA Neurol 2022; 79: 1148‐1154.
- 57. Loi SM, Eratne D, Kelso W, et al. Alzheimer disease: non‐pharmacological and pharmacological management of cognition and neuropsychiatric symptoms. Australas Psychiatry 2018; 26: 358‐365.
- 58. Ooms S, Ju YE. Treatment of Sleep Disorders in Dementia. Curr Treat Options Neurol 2016; 18: 40.
- 59. Withall A. The challenges of service provision in younger‐onset dementia. J Am Med Dir Assoc 2013; 14: 230‐232.
- 60. Cations M, Withall A, Horsfall R, et al. Why aren't people with young onset dementia and their supporters using formal services? Results from the INSPIRED study. PLoS One 2017; 12: e0180935.
- 61. Cations M, Day S, Laver K, et al. Post‐diagnosis young‐onset dementia care in the National Disability Insurance Scheme. Aust N Z J Psychiatry 2022; 56: 270‐280.
- 62. Craig D, Strivens E. Facing the times: a young onset dementia support group: Facebook style. Australas J Ageing 2016; 35: 48‐53.
- 63. Ritchie L, Egdell V, Danson M, et al. Dementia, work and employability: using the capability approach to understand the employability potential for people living with dementia. Work Employ Soc 2022; 36: 591‐609.
- 64. Millenaar J, Hvidsten L, de Vugt ME, et al. Determinants of quality of life in young onset dementia ‐ results from a European multicenter assessment. Aging Mental Health 2017; 21: 24‐30.
- 65. Millenaar JK, Bakker C, Koopmans RT, et al. The care needs and experiences with the use of services of people with young‐onset dementia and their caregivers: a systematic review. Int J Geriatr Psychiatry 2016; 31: 1261‐1276.
- 66. Bakker C, de Vugt ME, van Vliet D, et al. Predictors of the time to institutionalization in young‐ versus late‐onset dementia: results from the Needs in Young Onset Dementia (NeedYD) study. J Am Med Dir Assoc 2013; 14: 248‐253.
- 67. Cations M, Loi SM, Draper B, et al. A call to action for the improved identification, diagnosis, treatment and care of people with young onset dementia. Aust N Z J Psychiatry 2021; 55: 837‐840.
- 68. Manoochehri M, Huey ED. Diagnosis and management of behavioral issues in frontotemporal dementia. Curr Neurol Neurosci Rep 2012; 12: 528‐536.
- 69. O'Connor DW, Ames D, Gardner B, et al. Psychosocial treatments of behavior symptoms in dementia: a systematic review of reports meeting quality standards. Int Psychogeriatr 2009; 21: 225‐240.
- 70. Finkel SI, Costa e Silva J, Cohen G, et al. Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Int Psychogeriatr 1996; 8 Suppl 3: 497‐500.
- 71. Kales HC, Lyketsos CG, Miller EM, et al. Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus. Int Psychogeriatr 2019; 31: 83‐90.
- 72. Husebo BS, Ballard C, Sandvik R, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ 2011; 343: d4065.
- 73. Yunusa I, El Helou ML. The use of risperidone in behavioral and psychological symptoms of dementia: a review of pharmacology, clinical evidence, regulatory approvals, and off‐label use. Front Pharmacol 2020; 11: 596.
- 74. Ballard CG, Gauthier S, Cummings JL, et al. Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 2009; 5: 245‐255.
- 75. Ballard C, Corbett A, Howard R. Prescription of antipsychotics in people with dementia. Br J Psychiatry 2014; 205: 4‐5.
- 76. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta‐analysis of randomized placebo‐controlled trials. JAMA 2005; 294: 1934‐1943.
- 77. Harrison SL, Cations M, Jessop T, et al. Approaches to deprescribing psychotropic medications for changed behaviours in long‐term care residents living with dementia. Drugs Aging 2019; 36: 125‐136.
- 78. O'Connor DW, Ames D, Gardner B, et al. Psychosocial treatments of psychological symptoms in dementia: a systematic review of reports meeting quality standards. Int Psychogeriatr 2009; 21: 241‐251.
- 79. Bannon SM, Reichman M, Popok P, et al. Psychosocial stressors and adaptive coping strategies in couples after a diagnosis of young‐onset dementia. Gerontologist 2022; 62: 262‐275.
- 80. Millenaar JK, de Vugt ME, Bakker C, et al. The impact of young onset dementia on informal caregivers compared with late onset dementia: results from the NeedYD study. Am J Geriatr Psychiatry 2016; 24: 467‐474.
- 81. van Vliet D, de Vugt ME, Bakker C, et al. Impact of early onset dementia on caregivers: a review. Int J Geriatr Psychiatry 2010; 25: 1091‐100.
- 82. Kang M, Farrand S, Walterfang M, et al. Carer burden and psychological distress in young‐onset dementia: an Australian perspective. Int J Geriatr Psychiatry 2022; 37. https://doi.org/10.1002/gps.5765 [online ahead of print].
- 83. Millenaar JK, van Vliet D, Bakker C, et al. The experiences and needs of children living with a parent with young onset dementia: results from the NeedYD study. Int Psychogeriatr 2014; 26: 2001‐2010.
- 84. Hutchinson K, Roberts C, Roach P, et al. Co‐creation of a family‐focused service model living with younger onset dementia. Dementia (London) 2020; 19: 1029‐1050.
- 85. Australian Government Department of Social Services. Young people in residential aged care. https://www.dss.gov.au/disability‐and‐carers/programmes‐services/for‐people‐with‐disability/younger‐people‐with‐disability‐in‐residential‐aged‐care‐initiative (viewed Nov 2022).
- 86. Day S, Roberts S, Launder NH, et al. Age of symptom onset and longitudinal course of sporadic Alzheimer's disease, frontotemporal dementia, and vascular dementia: a systematic review and meta‐analysis. J Alzheimers Dis 2022; 85: 1819‐1833.
- 87. Moore KM, Nicholas J, Grossman M, et al. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study. Lancet Neurol 2020; 19: 145‐156.
- 88. Loi SM, Tsoukra P, Chen Z, et al. Risk factors to mortality and causes of death in frontotemporal dementia: an Australian perspective. Int J Geriatr Psychiatry 2021; 37. https://doi.org/10.1002/gps.5668 [online ahead of print].
- 89. Gerritsen AAJ, Bakker C, Verhey FRJ, et al. Survival and life‐expectancy in a young‐onset dementia cohort with six years of follow‐up: the NeedYD‐study. Int Psychogeriatr 2019; 31: 1781‐1789.
Summary