Abstract
Objective: To estimate the incidence of early-onset dementias in a defined area of Cambridgeshire served by Addenbrooke’s Hospital.
Methods: The area selected for the study was that covered by the local authority areas of Cambridge City, East Cambridgeshire, and South Cambridgeshire. Cases were identified from the specialist memory and dementia clinics held at Addenbrooke’s Hospital and were defined as those patients resident in the target area at the time of diagnosis, who were diagnosed with dementia before the age of 65 years between June 1, 2000, and May 31, 2006.
Results: No obvious pattern by sex was present. The incidence for all cases of primary dementia for the age range 45–64 years was estimated to be 11.5 cases per 100,000 person-years (95% CI 8.6–15.0). The incidence of frontotemporal dementia for the age range 45–64 years was estimated to be 3.5 cases per 100,000 person-years (95% CI 2.0–5.7); for Alzheimer disease the incidence for the same group was 4.2 (95% CI 2.5–6.6) and for Huntington disease the incidence rate of cases becoming affected (with or without dementia) was 0.8 (95% CI 0.2–2.3).
Conclusion: If the incidence rates were extrapolated across England and Wales, in the region of 460 new cases of frontotemporal dementia and 550 new cases of Alzheimer disease could be expected each year in the 45–64 years age group.
Glossary
- AD=
- Alzheimer disease;
- FTD=
- frontotemporal dementia;
- HD=
- Huntington disease;
- MCI=
- mild cognitive impairment;
- MND=
- motor neuron disease.
While they are uncommon, early-onset dementias (at age <65 years) place great demands on health services. Estimates of prevalence for early-onset Alzheimer disease (AD) over the last quarter of a century have varied between 15.1 and 43.9 cases per 100,000 population aged 45–65 years1–7 and for frontotemporal dementia (FTD) between 4 and 15 cases.1,8 The incidence of early-onset AD in the United Kingdom was estimated to be 7.2 per 100,000 in the 45–64 year age group in a 1993 study,7 but currently no incidence data exist for FTD in the United Kingdom.
While FTD is a rare condition, the behavioral symptoms that form part of the clinical presentation mean that this group of patients place a significant burden on caregivers and services, and so incidence data for this disorder would be very useful. We were able to identify a single study from Rochester, MN, that estimated the incidence of FTD.9 These authors identified new cases for the years 1990 through 1994 using historical diagnoses of FTD, and applying retrospectively the 1998 consensus criteria for FTD10 to all cases of dementia diagnosed during this time period. The incidence of FTD (per 100,000 person-years) was estimated to be 2.2 for 40–49 years, 3.3 for ages 50–59, and 8.9 for ages 60–69 years.
In this study, we investigated the incidence of FTD and other early-onset dementias in a geographically defined area of Cambridgeshire served by Addenbrooke’s Hospital in which we have previously established prevalence.1 The investigation covered the 6-year period between 2000 and 2006, with the advantage that all cases of FTD were diagnosed prospectively using the 1998 consensus criteria.
METHODS
Population.
This incidence study covers three local authority areas in Cambridgeshire, as described.1 The total population for these areas combined (midyear estimate 2003) is 326,200, with 75,600 aged 45–64 years. There is a balanced sex distribution across the age groups in the study and the full range of socioeconomic circumstances and urban-rural populations are represented in this area, although ethnic minority groups are underrepresented, with white ethnic groups making up 95% of the population compared to 91% of England and Wales as a whole. Cambridgeshire is an area of net population growth in working age groups and there is higher than average in and out migration due to the large student population at the university.
Patients.
The earlier prevalence study in the same geographical area used multiple sources of case ascertainment and one of the key findings was that all prevalent cases of early-onset AD and FTD in the target area were already known to the specialist memory and early-onset dementia clinics held at Addenbrooke’s Hospital. These specialist clinics were established in 1990 and evaluate 300 new patients per annum drawn from the Eastern region of England. Half of the referrals are from general practitioners in Cambridgeshire and the other half come from other specialists in the East of England. Based on our extensive prevalence survey it is extremely unlikely that incident cases would be referred out of the area given the reputation of the clinics both for service provision and for research particularly in the field of younger onset dementia.11 Moreover, there are close links between the neurology-based clinics and the psychiatry services so that patients presenting to psychiatric services with suspected dementia are referred for evaluation to the neurology clinics. All referrals undergo a comprehensive evaluation involving neurologic, psychiatric, and neuropsychological evaluation plus an MRI scan with coronal images to detect patterns of atrophy associated with FTD and AD. Diagnosis was reached by consensus at a multidisciplinary meeting and all cases were kept under review in the clinic. A multidisciplinary Huntington disease (HD) clinic that supports patients and carers in the Eastern Region of the United Kingdom has also been established at the hospital since 1991. The primary sources of case identification were therefore the databases of the early-onset, memory, and HD clinics. Secondary sources of case ascertainment were the clinical psychology services and the community-based early-onset dementia coordinators of the study and surrounding areas. Data were not sought from other hospitals as Addenbrooke’s is the regional center and referral of patients in the study area to hospitals outside the region is unlikely for the reasons outlined above.
Cases were those patients, resident in the target area at the time of diagnosis, who were diagnosed with dementia between June 1, 2000, and May 31, 2006, when aged less than 65 years. Additionally, patients were identified who were diagnosed by the specialist clinics when aged 65 years and over, but who gave a history of symptom onset during the study period when they were aged under 65 years. Collection of data for this second group allowed the investigation to be aware of the greatest possible number of incident cases during the period of investigation, however, the diagnostic uncertainty around these patients meant that they were not added to the main group for analysis.
Diagnosis.
Standard diagnostic criteria were applied in the clinic for AD,12 FTD,10 progressive supranuclear palsy,13 dementia with Lewy bodies,14 vascular dementia,15 alcoholic dementia,16 Parkinson disease,17 multisystem atrophy,18 and dementias secondary to specific causes. The presence of apraxia or alien hand and asymmetric parkinsonism was required for the diagnosis of corticobasal degeneration. FTD cases were further subcategorized into the following variants in keeping with other studies from Cambridge: behavioral variant FTD, FTD with motor neuron disease (MND), progressive nonfluent aphasia, and semantic dementia.
Patients with HD were considered affected if the Unified Huntington’s Disease Rating Scale19 score was greater than 5 and were further classified according to whether dementia was present or absent.
Analysis.
Incidence rates for the age group 45–64 years were calculated. The number of person-years at risk was estimated from census population estimates from 2003, the midpoint of the study. Ninety-five percent CIs were calculated using the Poisson distribution.
RESULTS
A total of 79 potential cases were identified from the primary sources. Fifteen patients who had a diagnosis of mild cognitive impairment (MCI) were excluded. Nine patients were diagnosed with dementia when aged 65 years or over, but gave a history of onset of symptoms between the ages of 45 and 64 years. These cases were comprised of one man and three women with AD, two women with FTD, two men with parkinsonian syndromes, and one woman with vascular dementia. Dementia is often of insidious onset, and due to uncertainty about the date and location at which these patients first became ill, these patients were excluded from the analysis. One case who did not have a final diagnosis was also excluded. A total of 54 cases were therefore identified from the primary sources. No additional cases were identified by secondary sources. Of the cases identified, 28 were men and 26 women (tables 1 and 2).
Table 1 Diagnosis by sex for incident cases of dementia, Cambridgeshire, 2000–2006
Table 2 Incident cases of dementia by sex and 5-year age bands
No obvious pattern by sex was present. The incidence of primary dementia (new cases per 100,000 person-years, men and women together) for the age range 45–64 years was estimated to be 11.5 (95% CI 8.6–15.0). The incidence of AD was estimated to be 4.2 (95% CI 2.5–6.6). The incidence of FTD for the same age range was estimated to be 3.5 (95% CI 2.0–5.7). Of the 16 patients with FTD, the majority (12) had behavioral variant FTD, 1 had FTD associated with MND, and 3 had language predominant FTD (2 semantic dementia and 1 progressive nonfluent aphasia). The incidence rate of HD (with or without dementia) was 0.8 per 100,000 person-years (95% CI 0.2–2.3). Many patients at risk of having HD do not go for testing; therefore the number of new cases may be higher than that cited here, although patients with HD dementia would present to medical attention.
DISCUSSION
The incidence of FTD of 3.5 per 100,000 person-years (45–64 year age group) was remarkably consistent with the earlier Rochester, MN, study that found an overall incidence rate for the population aged 40–69 years of 4.1 per 100,000 person-years (95% CI 1.1–10.4). We have not calculated age-specific incidence rates due to the small number of cases identified in our study. The incidence of early-onset AD of 4.2 per 100,000 person-years (45–65 years) (95% CI 2.5–6.6) was comparable to the earlier UK estimate of 7.2 per 100,000.
The study was limited to a small geographic area and yielded, therefore, a relatively small number of cases. It has the benefit of being based on a well established and very busy early-onset dementia clinical service and the fact that all patients were diagnosed prospectively in a specialist clinic using standard protocols, neuropsychological evaluation, and imaging, allowing us to accurately subclassify dementia types.
In this study we undertook an extensive reiterative approach to case ascertainment involving multiple secondary sources but failed to find cases with primary dementias that were not already known to the specialist clinic, which is perhaps not surprising given the centralization of services in Cambridgeshire and the longstanding reputation of the memory and early-onset dementias clinics.
The ratio of incident cases of AD to FTD was 1.2:1. This is similar to the ratio of 1.6:1 found in the prevalence study at this center. Other studies have reported the ratio of AD to FTD to be in the region of 4:1, and as discussed in the earlier article, this difference may be attributable to methods of case ascertainment, with the comprehensive assessment at the clinics excluding patients with memory problems due to depression or those given a diagnosis of MCI. Fifteen patients with MCI were excluded from our analysis, and it is possible that some of these cases would have been included as cases in earlier studies of AD. If these are incorporated into the current analysis, the incidence of AD per 100,000 person-years (45–65 years) increases to 7.5. This would put the ratio of AD to FTD as 2.3:1.
Estimates of the prevalence and incidence of young onset dementia allow for the appropriate provision and planning of services for patients and their families. If the incident rates from the main analysis were extrapolated across England and Wales, then we could expect in the region of 460 new cases of FTD in the 45–64 years age group each year and 550 new cases of AD.
ACKNOWLEDGMENT
The authors thank Jing Xie, Marie Breedon, Cath Burley, Jo Clark, Liz Carter, Lynne Denton, Jim Leadbetter, Sarah Mason, Ann Kershaw, Nick Oliver, Rachel Wenman, and the Young Onset Dementia Service at Cambridge and Peterborough Mental Health Partnership NHS Trust.
Footnotes
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Disclosure: The authors report no disclosures.
Received March 29, 2008. Accepted in final form August 5, 2008.
REFERENCES
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