Amsterdam Dementia Cohort: Performing Research to Optimize Care

Abstract

The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients forming the Amsterdam Dementia Cohort number almost 6,000 individuals. In this cohort profile, we provide an overview of the results produced based on the Amsterdam Dementia Cohort. We describe the main results over the years in each of these research lines: 1) early diagnosis, 2) heterogeneity, and 3) vascular factors. Among the most important research efforts that have also impacted patients' lives and/or the research field, we count the development of novel, easy to use diagnostic measures such as visual rating scales for MRI and the Amsterdam IADL Questionnaire, insight in different subgroups of AD, and findings on incidence and clinical sequelae of microbleeds. Finally, we describe in the outlook how our research endeavors have improved the lives of our patients.

Keywords: Alzheimer’s disease; Amsterdam Dementia Cohort; dementia; diagnosis; heterogeneity; mild cognitive impairment; prognosis; vascular factors.

Fig.1

The pie charts show initial diagnoses in the Amsterdam Dementia Cohort, according to age-at-onset. The pie charts are based on 5,960 patients who formed the Amsterdam Dementia cohort in September 2017. At younger age, the most frequent diagnosis is SCD, followed by AD. In the older age group, AD and MCI are the two most frequent diagnoses. Due to the relatively young age of the patients visiting our center, more rare diagnoses such as frontotemporal dementia are relatively frequent. AD, probable and possible Alzheimer’s disease; VaD, vascular dementia; FTLD, frontotemporal lobar degeneration, includes both behavioral variant FTD and primary progressive aphasia; DLB, dementia with Lewy bodies; Dementia other include other types of dementia such as Creutzfeldt-Jakob disease, corticobasal degeneration, progressive supranuclear palsy, and alcohol dementia; MCI, mild cognitive impairment.

Fig.2

In this cohort profile, we provide an overview of the results produced using data from the Amsterdam Dementia Cohort. We follow the structure of our research lines and describe the main results over the years, ending each part with a wrap up describing what has been achieved, and which are the open questions we are working on. Finally, we describe in the outlook whether and how our research endeavors have improved the lives of our patients.

Fig.3

When we compared CSF Aβ between older and younger patients, we found that early and late onset AD patients had similarly low levels of Aβ. Discriminatory value seems better in younger patients, but this is attributable to younger controls having higher concentrations of Aβ than older controls. In view of the limited associations between amyloid burden and severity of disease, limited associations with phenotypic variation could be expected. Indeed, when we used [¹¹C]PIB PET to estimate global amyloid-burden in younger and older AD patients, we found no differences between groups [119]. However, when we looked at the regional distribution of amyloid we found a subtle difference, with younger AD patients having a higher amyloid load in the parietal cortex than older patients. We found a similar effect when we compared AD subgroups based on APOE ɛ4 genotypes, with ɛ4 noncarriers having more frontal amyloid binding [120].

Fig.4

An axial MRI image of a susceptibility weighted image (SWI) that provides information on the presence of microbleeds (arrows; occipital part of the cortex). This is an image of a 68-year-old male with a diagnosis of Alzheimer’s disease. On presentation, he had an MMSE of 23. On MRI, there was evidence of moderate atrophy of the medial temporal lobe, mild global cortical atrophy, beginning confluent white matter hyperintensities and multiple microbleeds (mostly with a lobar location).