Young Onset Dementia in Central Norway

Background and objective Dementia is one of the most frequent causes of illness and death in the world, and has social and economic impact on people and communities worldwide. Alzheimer’s disease is the leading cause of all dementia, a syndrome caused by cognitive impairment interfering with the performance of everyday activities. It is characterized by a slowly progressive deterioration of cognitive functions such as memory, orientation and speech. As is the case for all neurodegenerative dementia disorders, Alzheimer’s disease develops over decades before eventually disrupting a person’s independency. Alzheimer pathology progresses in the brain at least a decade before signs of cognitive impairment appear. Often, several years pass before symptoms are recognized as such. For many years, the presence of dementia was obligatory for the diagnosis of Alzheimer’s disease. More recent diagnostic criteria have made it possible to diagnose the disease in the stage of mild cognitive impairment, a predementia phase characterized by cognitive impairment with preserved independency. In this stage, application of biomarkers was of particular importance. Diagnostic criteria for other neurodegenerative cognitive disorders have since developed in a similar way, with the positive effects of patients being recognized in an earlier phase, and researchers being able to identify dementing pathology at less advanced stages. Identification of disease as early as possible will be crucial in the event of medical treatment emerging in the future. Research on the epidemiological aspects of cognitive disorders can be challenging. As age is the major risk factor for dementia, the majority of research on cognitive disorders has focused on late onset dementia, characterized by symptoms appearing after the age of 65. However, dementia is not limited to older populations. Although research is scarce, younger persons can also be affected. Young onset dementia is defined as dementia occurring before the age of 65. As young onset dementia is a low frequency condition, research on epidemiological aspects is especially laborious, and requires a larger catchment area compared to studies on older populations. A majority of studies presenting epidemiological estimates of dementia have typically been designed to target disabilities among persons above the age of 60 to 70 years, leading to the specific bias of low numbers in younger subgroups. The estimates of young onset dementia provided in these studies are therefore of lower precision, though frequently cited in research, and by governments budgeting the costs of healthcare. There have only been a few publications focusing on the prevalence and incidence of dementia in younger persons. In these studies, estimates vary substantially. Differences in study design, cultural attitudes, as well as disparities within the healthcare systems, account for most of the discrepancies. Importantly, some studies are based on high quality dementia registries or tertiary clinics, others are community based; the former providing better diagnostics and higher specificity, the latter a lower level of diagnostic verification but higher sensitivity. Though young patients are likely to be assessed in hospitals, consensus exists that a population-based approach is preferred. The main object of “UngDemens I Trøndelag” was to explore epidemiological aspects of young onset dementia in a defined catchment area in central Norway (Trøndelag). A large population, in combination with a multiple sourced case ascertainment process, the routine employment of biomarkers such as magnetic resonance imaging and cerebrospinal fluid analysis in hospitals, and a meticulous review of every participant included, provided us with a relatively large dataset of high clinical accuracy. The first and second publication provided estimates on the prevalence, incidence and subtypes of dementia, while the third article focused on the diagnostic delays and the pathway to diagnosis for young onset Alzheimer’s disease, a frequent cause of dementia among people under the age of 65. Material and methods. Materials and methods The project was performed in Trøndelag, a geographically and administratively defined area with a population of almost 450 000. Trøndelag is heterogeneous in the distribution of urban and rural areas, hospital sizes, and the population is representative of that of the rest of the country. Healthcare in Norway is largely publicly organized, and readily accessible. All patients are assigned to a general practitioner, usually responsible for all referrals to hospitals. Though a diagnosis of dementia in the elderly is frequently made by community healthcare services, patients with suspected cognitive impairment under the age of 65 are evaluated by a qualified hospital physician. The primary source of patient identification was the Department of Neurology, University Hospital of Trondheim, and the memory clinic of the Department of Psychiatry, Levanger Hospital. Both departments are main referral sites of YOD in their catchment area, covering over 90 % of the target area. Secondary sources were hospital records from all three hospitals in the target area, specialized outpatient services for individuals with intellectual disabilities in both Trondheim and Levanger, and collaborating physicians in relevant hospital departments in Trøndelag. At a community level we worked closely with dementia coordinators and other relevant healthcare workers in frequent contact with young patients with cognitive disorders. Healthcare workers at every nursing home were individually contacted by telephone to ensure patients at all stages of the disease were identified. A regional centre for Huntington’s disease provided information on patients with dementia. The inclusion period was between July 2014 and July 2018. The project accepted all patients diagnosed with young onset dementia or mild cognitive impairment due to Alzheimer’s disease. Patients were individually verified by researchers either by personal assessment, or by reviewing referrals from the general practitioner and relevant hospital notes. A telephone interview with a close family member was conducted. The project collected various data on demographics, time lags, initial symptoms, and results of hospital investigations. Included patients were either consenting or non-consenting. In cases where patients did not consent, the Regional Committee for Medical and Health Research Ethics allowed the project to include participants to the extent that we only collected data on age, sex and diagnosis. Validated diagnostic criteria were applied for all diagnoses. Results The project identified a total of 410 patients who met the inclusion criteria. Of these, 390 patients had a diagnosis of dementia on census day. Close to 80 % of dementias were caused by a neurodegenerative disease in an otherwise heterogeneous group of dementia subtypes, identifying 17 different causes in total. Alzheimer’s disease was the most frequent cause of dementia, accounting for approximately 55 % of all dementias. There were no significant differences in sex. A total of 171 of the prevalent cases were between the age of 30 and 64 on census date, yielding a prevalence of 85.5 per 100 000 persons at risk in the age category of 30-64 years, and 143.1 per 100 000 in the age category of 45-64 years. The prevalence of the most common subtypes of dementia were calculated, Alzheimer’s disease being the largest displaying a prevalence of 37.0 and 65.4 per 100 000 persons at risk in the respective age categories. The project also produced prevalence rates for both dementia and most prevalent subtypes according to age (in five-year bands) and sex. To provide incidence rates for the same age groups, we identified patients diagnosed with dementia in the years 2015, 2016 and 2017. A total of 89 incident cases of dementia were identified, resulting in an incidence of 14.8 and 25.0 per 100 000 person-years for the age range 30-64 and 45-64, respectively. Corresponding incidence rates for Alzheimer’s disease were 6.7 and 11.8 per 100 000 person-years. The distribution of subtypes was similar to the prevalent cases; diverse, dominated by neurodegenerative disease, and AD causing almost half of all dementias. A total of 41 males and 48 females were identified, resembling the sex distribution in the prevalence study. A total of 223 patients diagnosed with typical young onset Alzheimer’s disease were included in a study of the diagnostic delays among these patients. Patients with mild cognitive impairment were included if biomarkers displayed signs of Alzheimer’s pathology, fulfilling 2007 International Work Group criteria for Alzheimer’s disease. The diagnosis of mild cognitive impairment due to Alzheimer’s disease was more frequent after 2012, accounting for 43 of the total 45 patients who received a diagnosis in the pre-dementia phase. Time from onset of symptoms to diagnosis was 5.5 years. The time from onset to initial contact with the healthcare system, mainly through the general practitioner, was almost three and a half years. Time from contact to first visit at the hospital exceeded ten months, resulting in a period of almost 15 months of clinical investigations, and over five visits, before AD was diagnosed. Mini Mental Status Evaluation was normal in most patients, or only marginally pathological when performed for the first time. The analysis of cerebrospinal fluid core biomarkers was performed eight months after the patient’s first visit to the hospital