The 90+ Study|
|- candidate number||24382|
|- NTR Number||NTR5867|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||20-mei-2016|
|- Secondary IDs||2015.374 NL53756.029.15|
|- Public Title||The 90+ Study|
|- Scientific Title||Study to identify factors associated with resilience to clinical dementia at old age|
|- ACRONYM||90+ Study|
|- hypothesis||The main outcome is the identification of clinical, biochemical, and genetic factors associated with resilience to cognitive decline in extreme elderly subjects. At baseline we will test the association between cognitive resilience and amyloid aggregation, neuropsychological, clinical, and physical markers, brain connectivity as assessed by electroencephalography (EEG), magnetoencephalography (MEG) or Magnetic Resonance Imaging (MRI), brain atrophy as assessed by MRI, vascular changes as assessed by MRI, retinal imaging or duplex of the carotid arteries, genetic markers, and CSF and blood (plasma, serum, RNA, DNA) markers.|
|- Healt Condition(s) or Problem(s) studied||Alzheimer, Dementia, Aged|
|- Inclusion criteria||To be eligible for this study, candidates must meet all of the following criteria:|
• Age ≥ 90 years
• Candidate is able to walk 400 meter independently (with or without walking aid)
• No significant visual or hearing impairment (as judged by clinician)
Cognitively intact group (cases):
o MMSE ≥ 27 points
o Clinical Dementia Rating (CDR) = 0.0 points
Demented group (control):
o MMSE: 20-28 points inclusively
o Clinical Dementia Rating (CDR) ≥ 1 point(s)
o Determination that this dysfunction is due to cognitive functional loss and not physical impairment, as judged by a neurologist or internist-geriatrician.
|- Exclusion criteria||A potential participant who meets any of the following criteria will be excluded from participation in this study:|
• Clinical diagnosis of severe AD
• Severe head trauma, with loss of consciousness
• Brain tumour (past, present)
• Schizophrenia, bipolar disorder, or recurrent psychotic disorders
• Stroke resulting in physical impairment
• Non-AD neurodegenerative disorders (e.g. Huntington disease, cortical basal degeneration, multiple system atrophy, CreutzfeldtJacob disease, primary progressive aphasia, Parkinson’s disease, diffuse Lewy body disease, frontotemporal dementia, primary vascular dementia)
• Epilepsy, currently using antiepileptic drugs (AEDs)
• Brain infections (e.g. herpes simplex encephalitis)
• Cancer with terminal life expectancy (life expectancy <12 months)
• Cancer chemotherapy or radiotherapy within the last 3 months
• Known B12 vitamin deficiency without treatment
• Uncontrolled diabetes mellitus (last measure HbA1c >80 mmol/mol)
• Known thyroid disease without treatment
• History of recreational drug use
• Alcohol consumption: >35 units per week (1 unit = 10ml of pure alcohol)
• Physical morbidity or illness which will not permit attendance at visit sessions
• Contraindication for MRI (e.g. metal implants, pacemaker etc.)
• Medications that may impair cognition, at the discretion of the investigator, e.g.:
o Benzodiazepine with known effects on cognitive functioning
o Lithium carbonate
o Antipsychotics including atypical agents
o Antidepressants with known effects on cognitive functioning
o Parkinson’s disease medicines
|- mec approval received||yes|
|- multicenter trial||no|
|- planned startdate ||17-mei-2016|
|- planned closingdate||31-dec-2017|
|- Target number of participants||74|
|- Primary outcome||The primary objectives are:|
1. To understand how clinical markers and biomarkers previously identified (and published) in younger and older dementia cohorts apply to the extreme elderly.
2. To identify novel biomarkers linked with resilience to developing AD in extreme elderly subjects.
|- Secondary outcome||The secondary objectives are:|
1. Generate normative data for the oldest old.
2. To measure the concordance between amyloid pathology as assessed in CSF and by PET in the oldest old.
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| N. Legdeur|
|- CONTACT for SCIENTIFIC QUERIES|| N. Legdeur|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale: It is estimated that 35.6 million people over age 60 years lived with dementia worldwide in 2010. In the US, the oldest old individuals (85+ years old) represent the fastest growing segment of the population; the number of oldest old living with dementia in the US could grow from 1-2 million in 2010 to more than 8 million by 2050 or 2060. Thus, improved diagnostic criteria and neuropsychological norms are urgently needed to ensure accurate diagnosis in this specific population. A full understanding of the prevalence of dementia among the oldest old of different socioeconomic, ethnic, and racial backgrounds is also required. Of specific interest to us is the need to gain a better understanding of the characteristics/traits/biomarkers associated with resilience to dementia to a fraction of the oldest old who are able to maintain age appropriate cognitive function. |
Patients/volunteers will be asked to participate in a study evaluating their cognitive function, amyloid load (analysis of biomarkers in the CSF obtained via lumbar puncture and amyloid PET imaging), genotyping, and phenotyping across a number of visits.
Objective: The main objectives are to understand how clinical markers and biomarkers previously identified in younger and older dementia cohorts apply to the extreme elderly (90+ years old) and to identify novel biomarkers linked with resilience to developing Alzheimer’s disease (AD) in extreme elderly subjects.
Study population: We will enrol 60 cognitively normal subjects and 60 subjects suffering from cognitive impairment, 90+ years old, from EHR, the Manchester and Newcastle Aging Study (MNAS), and the VUmc.
Main study parameters/endpoints: The main outcome is the identification of clinical, biochemical, and genetic factors associated with resilience to cognitive decline in extreme elderly subjects. At baseline we will test the association between cognitive resilience and amyloid aggregation, neuropsychological, clinical, and physical markers, brain connectivity as assessed by electroencephalography (EEG), magnetoencephalography (MEG) or Magnetic Resonance Imaging (MRI), brain atrophy as assessed by MRI, vascular changes as assessed by MRI, retinal imaging or duplex of the carotid arteries, genetic markers, and CSF and blood (plasma, serum, RNA, DNA) markers.
|- Main changes (audit trail)|
|- RECORD||20-mei-2016 - 6-jul-2016|
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