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This project comprises of two complementary parts. One part is aimed at the development of innovative diagnostic techniques to detect molecular signatures of AD based on disturbances of amyloid metabolism and glutamate neurotransmission. In this part, the focus is on the two most promising diagnostic approaches in AD: (molecular) imaging techniques and molecular diagnostic tests of CSF. In the second part of this study, techniques for which proof-of-concept has been found in humans are applied in a large group of AD patients. These patients are recruited in an established network of 4 collaborating memory clinics in The Netherlands, which use a standardized diagnostic protocol and share an extensive common database. Furthermore, more mature molecular, structural, and functional imaging and molecular diagnostic CSF techniques as well as the conventional diagnostic work-up will be applied from the start of the study in patients from the same network of memory clinics.

Current evidence on older adults is derived from population-based cohort studies and randomized controlled trials, which may not include frail individuals. Data are lacking on older outpatients, a potentially diverse population. To bridge the gap between current evidence and clinical practice needs, the Milan Geriatrics 75+ Cohort Study was designed as an observational hospital-based outpatient cohort study. This study included 1861 new consecutive outpatients aged ?75 years who attended a first comprehensive visit at the Geriatric Unit of ‘I.R.C.C.S. Ca’ Granda’ in Milan, Italy, in the period between January 3, 2000 and March 25, 2004. These participants routinely underwent an extensive standardized structured medical examination and comprehensive geriatric assessment with trained physicians. At baseline, data were collected on reason for referral, demographics, physiological anamnesis, past and present medical history and medication use. Moreover, medical examination and anthropometric measurements were performed. Cognitive function was assessed using the 30-item Mini-Mental State Examination (MMSE). Functional status was evaluated using Katz’ Activities of Daily Living (ADL) and Lawton’ Instrumental Activities of Daily Living (IADL) questionnaires. At 10-year follow-up, all-cause mortality was assessed by collecting data from the Register Office of Milan or other town of residence.

Last Update 21/09/2017

Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia in older people. The aim of LewyPro is to examine and characterise symptoms and brain changes during the prodromal period of LBD. Earlier diagnosis is important because it facilitates care planning, leads to earlier treatment of cognitive symptoms and enables earlier identification of other symptoms, including parkinsonism.

Lewy Pro is recruiting a group of people with mild cognitive impairment (MCI) and prodromal symptoms suggestive of Dementia with Lewy Bodies (DLB) and following them up annually to assess biomarker changes and clinical course. The initial assessment will include a detailed clinical assessment, a blood sample, a lumbar puncture for cerebrospinal fluid, and a DaTSCAN.

Last Update 21/09/2017

The ADC was setup in 2004 by including all patients who come to the Alzheimer Center for diagnostic work up and who consent to give all data, collected as part of the routine diagnostic work up, for research. The aim is and was to facilitate research into new and existing biomarkers in the broadest sense, to establish diagnostic, prognostic and theragnostic values and further insight into the pathogenesis of neurodegenerative dementias. The data are collected on a weekly basis and consist of baseline data and annual follow up data. Since it is conception it has grown into one of the largest clinical databases in the dementia field. More info on setup, characteristics and data collection can be found in van der Flier WM, Pijnenburg YA, Prins N, Lemstra AW, Bouwman FH, Teunissen CE, van Berckel BN, Stam CJ, Barkhof F, Visser PJ, van Egmond E, Scheltens P.

Optimizing patient care and research: the Amsterdam Dementia Cohort. J Alzheimers Dis. 2014;41(1):313-27. doi: 10.3233/JAD-132306. PubMed PMID: 24614907.

Last Update 21/09/2017

In this epidemiological study we examined the prevalence of medical comorbidity in elderly subjects with cognitive deficits and dementia. The ReGAl Project (Rete Geriatrica Alzheimer- Geriatric Network on Alzheimer’s disease) collected data in 33 Italian Geriatric memory clinics from January 2001 to December 2005. A total of 4,075 patient were recruited.

Last Update 21/09/2017

The Swedish BioFINDER Study consists of four cohorts where patients are included prospectively and followed longitudinally (www.biofinder.se). At baseline, these individuals undergo detailed and standardized cognitive, neurological and psychiatric examinations. Plasma, blood, CSF and samples for cell biology studies are collected. Most also have also undergone advanced Magnetic Resonance Imaging, and in many of the non-demented cases Amyloid and Tau positron emission tomography (PET) imaging have also been done.

The subcohorts include:
i) Healthy volunteers. Ca 350 volunteers aged 60-100 years old from the population-based Malm’ EPIC cohort (380 participants as of Feb 2016). Follow-up time: at least 8 years with investigations repeated every second year. In this cohort, appr. 20% is expected to have preclinical AD.
ii) Patients with Mild Cognitive Impairment (MCI) or Subjective Cognitive Decline (SCD). Ca 500 patients with MCI/SCD aged 60-80 years. Follow-up time: at least 6 years with investigations repeated every year. In this cohort, appr. 50% is expected to have prodromal AD.
iii) Patients with different dementia disorders. We include ca 250 dementia cases aged 40-100 years with AD, VaD, DLB, PDD or FTD. Follow-up time: at least 2 years with investigations repeated every year.
IV) Patients with Parkinson’s disease (PD) and PD-related disorders. Ca 300 patients with Parkinson-like symptoms. Follow-up time: at least 6 years with investigations repeated every year.

Last Update 21/09/2017

The German Study on Ageing, Cognition, and Dementia (AgeCoDe) in primary care patients is an ongoing multicenter prospective study in elderly individuals with a focus on the identification of risk factors and predictors of cognitive decline and dementia.
Between January 1, 2003 and November 30, 2004 a total of 3327 subjects free of dementia at baseline were recruited from general practitioner (GP) registries and assessed with structured clinical interviews and cognitive tests. Since then, participants as well as their proxies were interviewed by trained staff every 1.5 years. In 2016 follow-up 9 was completed.
Main inclusion criteria were ages greater than 75 years, native German language, absence of severe hearing or vision impairments, and residing at home rather than in an institution.
The approval of this study was provided by the local ethics committees of the Universities of Bonn, Hamburg, D’sseldorf, Heidelberg/Mannheim, Leipzig, and Munich. All subjects gave written informed consent before the participation in this study.

Of the 3,327 patients interviewed at baseline, 84.8% (n = 2,820) could be personally interviewed 1.5 years later and 73.9% (n = 2,460) 3 years later. For the vast majority of subjects who could not be personally interviewed, systematic assessments, focusing particularly on dementia, were obtained from GPs, relatives or caregivers.

Last Update 21/09/2017

AIBL is a study of over 2,000 people assessed over a long period of time (over 10 years) to determine which biomarkers, cognitive characteristics, and health and lifestyle factors determine subsequent development of symptomatic Alzheimer’s Disease (AD).

The baseline inception cohort consisted of:
i. 211 individuals with AD as defined by NINCDS-ADRDA (McKhann et al, 1984);
ii. 133 individuals with Mild Cognitive Impairment (MCI)
iii. 768 healthy individuals without cognitive impairment. This group included volunteers with at least one copy of the ApoE ?4 allele, volunteers without a copy of the ApoE ?4 allele and 396 volunteers who expressed subjective concern about their memory function.

The enrichment cohort consists of:
i. 142 individuals with AD
ii. 220 individuals with MCI
iii. 582 individuals with without cognitive impairment.

The data was collected through clinics and questionnaires.

Last Update 21/09/2017

The Irish Longitudinal Study on Ageing (TILDA) is a large-scale, nationally representative, longitudinal study on ageing in Ireland, the overarching aim of which is to make Ireland the best place in the world to grow old.
TILDA collects information on all aspects of health, economic and social circumstances from people aged 50 and over in a series of data collection waves once every two years. TILDA is unique amongst longitudinal studies in the breadth of physical, mental health and cognitive measures collected. This data, together with the extensive social and economic data, makes TILDA one of the most comprehensive research studies of its kind both in Europe and internationally.

Last Update 21/09/2017

The aim of the Alfa Study is to focus on the processes taking place before the initiation of Alzheimer’s symptoms in order to design interventions to prevent or delay the onset of dementia. Inclusion criteria were being cognitively normal Spanish and/or Catalan-speaking persons aged between 45 and 74 years that agreed with the study procedures and tests: clinical interview and questionnaires associated to risk factors, cognitive tests, a blood sample extraction for DNA analysis, and MRI.

A subset (n=450) of the ALFA parent cohort participants are currently being recruited / undergoing a nested longitudinal long-term study, named the ALFA+ study, in which a more detailed phenotyping will be performed. On top of a similar characterization as in the ALFA parent cohort, it will entail the acquisition of both wet (CSF, blood, and urine sample collection) and imaging (magnetic resonance imaging [MRI] and PET) biomarkers. Furthermore, ALFA parent cohort participants may also be invited to participate in other BBRC studies such the ALFAlife primary intervention study (n=400) or the full genetic and neuroimaging characterisation study referred to as ALFAgenetics (n=2000).

Last Update 21/09/2017