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A2 - Loi, 2021
A2 - Loi, 2021
DOI: 10.1002/gps.5424
RESEARCH ARTICLE
- Accepted: 3 September 2020
1
Neuropsychiatry, NorthWestern Mental
Health, Melbourne Health, Royal Melbourne Abstract
Hospital, Parkville, Australia
Objectives: Younger‐onset dementia (YOD) refers to a dementia where symptom
2
Department of Psychiatry, The University of
onset occurs when the patient is less than 65 years of age. YOD is far less common
Melbourne, Parkville, Australia
3
National Ageing Research Institute, Parkville,
than late‐onset dementia (occurring when patients are over 65 years old) and more
Australia challenging to diagnose due to its heterogeneous presentation. There have been
4
Department of Psychology, Monash relatively few studies describing demographic and diagnostic characteristics of
University, Clayton, Australia
5
patients with YOD in the community, particularly with follow‐up information.
Department of Medicine, Royal Melbourne
Hospital, Parkville, Australia Methods: A retrospective cohort study was performed of inpatients admitted to a
6
Population Health and Immunity Division, The tertiary neuropsychiatry service, located in metropolitan Victoria, Australia, from
Walter and Eliza Hall Institute of Medical
2009 to 2019. Inpatients with a YOD diagnosis were identified and data regarding
Research, Parkville, Australia
7 diagnosis, demographics and investigations were obtained.
Florey Institute of Neuroscience and Mental
Health, Parkville, Australia Results: There were 849 individual inpatients who were admitted to the service in
the 10‐year period and received comprehensive assessment. There were 306 in-
Correspondence
Samantha M. Loi, Melbourne Neuropsychiatry, dividuals who received a YOD diagnosis, using contemporaneous diagnostic criteria
NorthWestern Mental Health, Royal (frequency 36%). The most common diagnoses were Alzheimer's disease (24.2%),
Melbourne Hospital, John Cade Level 2,
Parkville, VIC 3050, Australia. frontotemporal dementia (23.1%), Huntington's disease (16.7%) and vascular de-
Email: [email protected] mentia (7.8%). More than half of these inpatients were followed up and 6.5% had a
diagnostic change when reviewed.
Funding information
National Health and Medical Research Conclusions: This study reports on the largest cohort of YOD to date, with diag-
Council, Grant/Award Number: GNT1138968;
nostic breakdown similar to previous retrospective file reviews. The neuropsychi-
Yulgilbar Alzheimer's Research Program
atry service is funded to follow‐up its patients, thus allowing re‐assessment and
continuity of care. While there are limitations in this study such as the lack of
neuropathological outcomes, the findings emphasise the strengths of follow‐up and
appropriate service provision for these patients.
KEYWORDS
dementia, neuropsychiatry, younger‐onset dementia
Int J Geriatr Psychiatry. 2020;1–8. wileyonlinelibrary.com/journal/gps © 2020 John Wiley & Sons Ltd.
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1 | INTRODUCTION
Key points
There are approximately 27,247 people living with younger‐onset
� There was a 36% frequency of younger‐onset dementia
dementia (YOD) in Australia.1 YOD has a heterogeneous range of
presentations and aetiologies and is associated with significant delays over 10 years, with Alzheimer's disease and fronto-
in diagnosis.2,3 As symptoms occur before the age of 65, people with temporal dementia being the most common causes of
YOD are often employed with young families and providing financial dementia
� Repeat assessment of younger‐onset patients is impor-
support, and the diagnostic delay and uncertainty result in distress
and adverse emotional effects on the individual and their families. 4 tant in terms of reviewing diagnostic stability
� Despite comprehensive assessment, people were diag-
The prevalence and diagnostic make‐up of YOD in Australia re-
mains unclear with no Australia‐wide epidemiological data available. nosed with a dementia of unknown aetiology
5
The available data is restricted to local and international epidemio-
logical6,7 and retrospective file reviews. Most recently, Withall et al.5
reported a prevalence of 68.2 per 100,000 in the Eastern Sydney re- provides outpatient follow‐up through several YOD clinics (including
gion and alcohol‐related dementia was cited as the most frequent YOD specialist Huntington's disease and predictive genetic clinics).
(18.4%), followed by Alzheimer's disease (AD) (17.7%). Previous Patients receive comprehensive clinical assessments including
prevalence studies have reported a lower rate,6,7 and AD and vascular neuropsychiatry, neurology, allied health and nursing observations.
dementia (VaD) were the most commonly occurring YODs. Investigations typically include neuroimaging, blood and cerebrospi-
Retrospective file reviews contribute to the scientific evidence nal fluid (CSF) analysis. Multidisciplinary clinical reviews are held bi‐
base by evaluating the clinical disease characteristics and course over weekly and diagnoses are made using contemporaneous consensus
time.8 While not epidemiological samples, they have yielded crucial criteria. Formal feedback and discharge planning is provided to the
information on clinical assessment and frequency of the different patient and their family at the end of the assessments. A compre-
aetiologies of YOD. The diagnostic ‘mix’ of YOD has varied, with AD hensive summary is provided to referring clinicians.
and frontotemporal dementia (FTD) being the two most commonly The study was approved on 14 November 2017 by the Mel-
reported YOD diagnoses.9,10 As well as dementia aetiology, risk bourne Health hospital research ethics committee (2016.038).
factors such as family history of dementia and cerebrovascular risk
factors have been investigated.11
Internationally, there have been no further epidemiological or 2.1 | Data sources
file review studies in YOD since 2014. There is an urgent need to
revise the frequency of the different types of YOD, obtain de- 1. Comprehensive discharge summaries. An initial list of inpatient
mographic details and evaluate the need for services. In addition, the admissions who had a discharge diagnosis of dementia was ob-
studies which have included longitudinal follow‐up of patients re- tained by searching the electronic discharge summaries of all
ported on diagnostic change.9,11 This suggests that for the highly admissions admitted to the inpatient unit from January 1 2009 to
heterogeneous YOD group, close follow‐up of patients is crucial to September 7 2019 (n ¼ 1097). The Hospital International Clas-
monitor diagnostic stability as this can have significant implications sification of Diseases Adapted codes for discharge diagnoses of
on management.12 ‘dementia’ and for other neurodegenerative disorders were used.
The main aim of this paper is to describe the characteristics of These terms included ‘cognitive impairment’, ‘Alzheimer's dis-
YOD patients attending a neuropsychiatry service in metropolitan ease’, ‘frontotemporal dementia’ and ‘Huntington's disease’ (see
Victoria, Australia. Specifically, we report on the clinical experience Table S1).
of a dedicated YOD service in order to provide a contemporaneous 2. A database (maintained weekly) listing all the inpatients and their
description of the diagnostic and demographic characteristics of a discharge diagnoses. SL searched this database manually to
YOD cohort. A secondary aim was to provide information regarding ascertain whether the electronic search had missed any additional
longitudinal diagnostic changes. dementia diagnoses, obtaining the details of individual patients
who had their ‘index’ admission to the unit from the above dates.
T A B L E 1 Demographics of 306 inpatients diagnosed with 3.3.4 | Risk factors for dementia
younger‐onset dementia
Number (%) Missing data (%) 26.7% of inpatients had a previous or current history of heavy alcohol
intake (n ¼ 88). Vascular risk factors (Table 2) were present in 63.4%
Men 156 (51.0) ‐
(n ¼ 194) of patients. People with VaD had the highest average
Location ‐ 3 (1.0)
number of risk factors, 2.8 (SD ¼ 1.3), which was significant (p <
Metropolitan 178 (58.2) ‐ 0.0001), F (10,205) ¼ 9.508, p < 0.0001.
Rural/regional 101 (33.0) ‐
Interstate 24 (7.8) ‐
3.3.5 | Family history
Location prior to admission ‐ 4.0 (1.3)
Home 229 (74.8) ‐ Similar proportions (65%) of inpatients had a family history of de-
Hospital 20 (6.5) ‐ mentia or psychiatric disorders. In terms of a ‘new’ psychiatric
diagnosis, 39% (n ¼ 120) had a new diagnosis of depression, 21.6% (n
Psychiatric inpatient unit 27 (8.8) ‐
¼ 66) a new diagnosis of psychosis and 3.6% (n ¼ 11) had a new
Residential facility 26 (8.5) ‐
diagnosis of mania or bipolar affective disorder.
Education ‐ 31 (10.1)
Primary 2 (0.7) ‐
Ninety‐nine patients (32.4%) had a lumbar puncture for CSF analysis. 4 | DISCUSSION
One hundred and two (33.3%) had genetic testing of which 72 (HD ¼ 51,
NPC ¼ 11) (71.3%) yielded a positive result. The majority of inpatients This retrospective cohort study aimed to report on the diagnoses of
had structural imaging (92.7%) and functional imaging (90.1%). YOD over a 10‐year period. We found that 36% of all inpatients
LOI ET AL.
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Behavioural‐variant FTD 46 (15.0) HSAN1 1 (0.6) 22 (47.8) 65.5 (19.3) 1.6 (0.8)
FTD MND 14 (4.5) C9orf72 5 (1.6) 8 (57.1) 67.5 (15.6) 1.5 (1.0)
PSP 2 (0.7) ‐ 0 0 ‐ ‐
c
Other 17 (5.6) CSF1R, SPG1 13 (76.5) ‐ ‐
Abbreviations: AD, Alzheimer's disease; CBS, corticobasal syndrome; FTD, frontotemporal dementia; MND, motor neuron disease; NOS, not otherwise
specified; NUCOG, Neuropsychiatry Unit Cognitive Assessment tool; PCA, posterior cortical atrophy; PNFA, progressive non‐fluent aphasia; PSP,
progressive supranuclear palsy; VaD, vascular dementia; YOD, younger‐onset dementia.
a
Includes Parkinson's disease dementia (n ¼ 12) and dementia with Lewy bodies (n ¼ 4).
b
Mean NUCOG scores not calculated for cerebellar degeneration, CBS and PSP due to small numbers.
c
Includes adrenoleukodystrophy (n ¼ 2) multiple sclerosis (n ¼ 2) and HIV‐related dementias (n ¼ 2).
referred to a neuropsychiatry service received a diagnosis of a YOD. disorder but was a common aetiology in this study, reflecting this
This is less than reported by Fujihara et al.20 and Panygeres et al.11 Neuropsychiatry's specialist expertise in the assessment, diagnosis
who reported frequencies of YOD at 45.3% and 49.5%, respectively. and treatment of HD, with established relationships with Hunting-
Shinagawa et al.21 compared YOD and older‐onset dementia pre- ton's Victoria, the peak consumer organisation for HD.
senting to their memory clinic and found a lower frequency of YOD We found age of symptom onset to be 51 years old (SD ¼ 13.4),
at 27.7%. The differences may be due to the types of patients with Ferran et al.9 and Fujihara et al.20 also reporting mean age of
referred and the service models of the clinics. Fujihara et al. (2004) onset in the early 50s. A prevalence study of YOD in Eastern Sydney
reviewed consecutive files for 6 years of patients attending a found age of onset to be 55 years old (SD ¼ 9.5),5 and a Japanese
cognitive clinic, whereas the clinic where Panygeres et al. (2007) and study reported age of onset of YOD to be 53.4 years old (SD ¼ 7.9).7
9
Ferran et al. reviewed files of patients who attended clinics run by None of the previous studies reported on the age of symptom onset
neurologists. The neuropsychiatry service is a psychiatry‐led clinic of the different types/diagnoses of YOD.
and thus receives many more referrals of patients who have psy- An almost 50:50 gender split between men and women diag-
chiatric conditions with possible cognitive and behavioural change. nosed with YOD was found in this study, similar to others10,11 and
Psychiatric conditions such as schizophrenia can have cognitive the Eastern Sydney prevalence study,5 but was slightly less compared
22
change, but this may not be diagnosed as a dementia per se. to Ferran et al.9 and Fujihara et al.20 These two studies have gender
With regards to YOD aetiology, similar to previous studies (see results consistent with epidemiological reports that more men are
Table 4), we found the three most common to be AD, FTD (behav- affected by YOD, compared to more women are affected by older‐
ioural‐ and language‐variants) and VaD. HD is a relatively rare onset dementia.23
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Follow‐up diagnoses
Initial diagnoses (n) AD VaD bv‐FTD Other FTDa Genetic DLB, PDD, MSA Other dementiab Dementia NOS
AD (5) ‐ ‐ ‐ 1 ‐ 2 1 1
Abbreviations: AD, Alzheimer's disease; bv‐FTD, behavioural‐variant FTD; CBS, corticobasal syndrome; DLB, dementia with Lewy bodies; FTD,
frontotemporal dementia; MSA, multiple system atrophy; NOS, not otherwise specified; PDD, Parkinson's disease dementia; PSP, progressive
supranuclear palsy; VaD, vascular dementia.
a
Includes FTD semantic (n ¼ 1) and FTD motor neuron disease (n ¼ 2).
b
Includes spastic paraplegia (n ¼ 1), vasculitis (n ¼ 1), Huntington's disease (n ¼ 1) and CBS (n ¼ 1).
c
Includes CBS (n ¼ 1) and PSP (n ¼ 1).
d
Includes psychotic depression (n ¼ 1) and depression (n ¼ 2).
The second aim was to report on diagnostic stability resulting methods in YOD in order to create a national YOD registry. This will
from follow‐up of these inpatients. The changes in diagnoses over the yield much more rich data about YOD in order to more easily, timely
10‐year period presents an interesting scenario. Panegyres et al. and accurately diagnose YOD and to monitor epidemiology in order to
(2007) reported on five changes; three who had an initial diagnosis of facilitate best practice guidelines. The utility of new investigative
FTD were shown to have a psychiatric disorder and one vice versa, processes such as amyloid PET and neurofilament light chain is likely
and one patient initially diagnosed with AD who was later re‐diag- to assist in more definitive diagnoses of YOD and accurately dis-
nosed with a psychiatric disorder. Ferran et al. (1996) described 183 tinguishing YOD from non‐neurodegenerative and psychiatric disor-
patients (out of their total of 200) who were re‐assessed after 12 ders.25 Following these patients over time may also provide
months. There were changes in dementia diagnoses, with 22 patients information regarding mortality rates in the different types of YOD.
who had AD, VaD and alcohol‐related dementia, re‐diagnosed with a The strengths of this study included the use of updated
different type of dementia and depression. There were also 42 pa- consensus criteria and a high follow‐up rate of the inpatients; how-
tients who had an ‘unknown’ diagnosis and after 12 months, two of ever, there were methodological limitations. The search process was
these continued to have the ‘unknown’ diagnosis. dependent on the dementia diagnosis which was annotated and while
Similarly, our study reiterates the importance of follow‐up as- we attempted to examine as many admissions as possible, some may
sessments for diagnostic stability. We had 6.5% of inpatients who had a have been missed. Similar to previous studies, there were small
diagnostic change, mostly from one type of dementia to another, numbers people with YOD from different ethnicities, so there con-
demonstrating that repeat assessment of neuropsychiatry, cognition tinues to be a lack of information in YOD in culturally and linguistic
and neuroimaging can be helpful in confirmation of or reformulating diverse populations. In addition, this study was based in a neuro-
diagnosis, which has implications for patients, families, and ongoing psychiatry service and referral bias may affect the proportions of
clinical management and research options. For example, patients who diagnoses. Although all patients received comprehensive multidisci-
received a re‐diagnosis of AD were started on a cholinesterase inhib- plinary assessments, multimodal investigations and diagnoses were
itor and were referred to a relevant AD clinical trial. We also found 15 based on established diagnostic criteria, other limitations include the
patients who initially had a dementia diagnosis but were re‐assessed to lack of follow‐up data for the remainder of inpatients we diagnosed
have a psychiatric disorder (subsequently excluded from analysis). This with YOD and thus the potential change of diagnosis may be under‐
emphasises the importance of appropriate diagnosis and service pro- or over‐estimated. We also lacked a definitive diagnosis from
vision in order to be able to follow‐up patients over time. neuropathological confirmation. Additionally, in a retrospective
Further adding weight to the need for longitudinal repeat as- study, not all relevant risk factors have been identified and recorded,
sessments is that our study still had 17 inpatients (5.6%) with a diag- potentially affecting any reported associations between risk factor
nosis of dementia NOS, similar to Ferran et al. (1996) who reported six and outcomes. Finally, another limitation is that many health pro-
patients (6%) who had unspecified dementia. More longitudinal fessionals have been involved in patient care, making the measure-
studies of YOD with rigorous follow‐up of neuropsychiatry, neuro- ment of risk factors and outcomes less consistent than that achieved
imaging, biomarkers and cognition will shed more light on the pro- with a prospective study design.
gression and prognosis of YOD has been recommended (Loi et al. This study reports on the aetiology of YOD and demographic de-
2020).24 Further research would include harmonisation of assessment tails, with the largest number of YOD cases in the literature. We used
LOI
ET AL.
Panegyres & Frencham Shinagawa et al. Fujihara et al. McMurtray et al. Ferran et al. Kelley et al.
This studya (2007)a (2006) (2004) (2006) (1996)a,b (2008)
Location Australia Australia Japan Brazil United States United Kingdom United States
Age onset (mean, SD) 51.0 (13.4) NR NR 51 (11.4) 51.5 (10.8) 52.6 (9.4) 34.7 (7.9)
Age at admission (mean, SD) 55.8 (9.2) NR 58.3 (11.0) 53.3 (12.1) 56.5 (9.8) 56 (9.3) 36.7 (7.8)
FTD (bv þ lang) 62 (20.2) 43 (38.4) (21.4) 7 (5.0) 7 (2.5) 7 (4.0) 31 (13.2)
Abbreviations: AD Alzheimer's disease; ARD, alcohol‐related dementia; DLB, dementia with Lewy bodies; FTD, frontotemporal dementia; HD, Huntington's disease; NR not reported; VaD, vascular
dementia; YOD, younger‐onset dementia.
a
Studies which followed up some patients with YOD.
b
Reviewed 200 consecutive files.
c
Includes posterior cortical atrophy and frontal AD.
d
Three patients with VaD and total of 14 had vascular disease.
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