Population & Study Design

Overview

Healthy elderly individuals

ENROLLMENT

Up to 600 cognitively healthy elderly are being included in this prospective, longitudinal cohort study between 2010 and 2016. The aim is to recruit a well-characterized control group for use in case-control studies within the field of dementia and parkinsonian disorders research. The study also aims to investigate neurodegenerative changes in preclinical stages of dementia disorders prior to the onset of symptoms. The participants were recruited by random sampling from a longitudinal population-based community cohort study in Malmö, Sweden (Malmö Diet and Cancer Study) and from this study epidemiological data, clinical examination, food-frequency questionnaire and blood sampling have been collected since the early 1990’s.

INCLUSION CRITERIA

• Absence of cognitive symptoms as assessed by a physician with special interest in cognitive disorders.
• Age ≥60 years
• MMSE score 28-30 at screening visit (27-30 at baseline visit).
• Do not fulfill the criteria for MCI or any dementia.
• Speaks and understands Swedish to the extent that an interpreter was not necessary for the patient to fully understand the study information and cognitive tests.

EXCLUSION CRITERIA

• Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
• Current significant alcohol or substance misuse.
• Refusing lumbar puncture.
• Refusing MRI.
• Significant neurological or psychiatric illness.

FOLLOW-UP FOR 8 YEARS

Every 24 months for up to 10 years full clinical, cognitive, neurological, and psychiatric evaluation as well as CSF/blood collection are performed. MRI is performed every 24 months for up to 6 years.

A subset of participants does not have repeated follow-ups but instead performs one follow-up at 6-8 years after inclusion, consisting of full clinical, cognitive, neurological, and psychiatric evaluation as well as CSF/blood collection.

Mild cognitive complaints (SCD & MCI)

ENROLLMENT

Within prospective, longitudinal study, 500 patients with mild cognitive complaints (either subjective cognitive disorder [SCD] or mild cognitive impairment [MCI]) have been consecutively included between 2010 and 2015 from the Memory clinic at Skåne University Hospital and Ängelholm Hospital in southern Sweden. All patients have been referred to the memory clinics due to subjective or objective cognitive impairment as part of routine clinical practice. Approximately 40-60% of the patients are expected to develop a dementia disorder such as Alzheimer’s disease, vascular dementia, dementia with Lewy bodies or Parkinson’s disease dementia.

INCLUSION CRITERIA

• Referred to the memory clinic at Skåne University Hospital or Ängelholm hospital in Sweden due to cognitive symptoms experienced by the patient and/or informant. These symptoms did not have to be memory complaints, but could also be executive, visuo-spatial, language, praxis or psychomotor complaints.
• Age between 60 and 80 years.
• MMSE score of 24 – 30 points at baseline visit.
• Do not fulfill the criteria for any dementia.
• Speaks and understands Swedish to the extent that an interpreter not was necessary for the patient to fully understand the study information and neuropsychological tests.

EXCLUSION CRITERIA

• Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
• Current significant alcohol or substance misuse.
• Refusing lumbar puncture or neuropsychological assessment.
• The cognitive impairment at baseline visit can with certainty be explained by another condition or disease such as normal pressure hydrocephalus, major cerebral hemorrhage, brain infection, brain tumor, multiple sclerosis, epilepsy, psychotic disorders, severe depression, alcohol abuse the last five years, on-going medication with drugs that invariably cause cognitive impairment (such as high-dose benzodiazepines).

CLASSIFICATION OF MCI

The patients are classified into MCI subtypes based on the neuropsychological assessment results. The normative standard scores are all transformed into z-scores and a mean z-score for each cognitive domain score is calculated. The main principle is that an impaired function is defined as a mean score ≤ -1.5 z-score. However, a higher performance can also be classified as MCI if this is considered to be significantly below estimated premorbid level of intellectual function (as determined by a neuropsychologist’s judgment based on the patients’ education and the results of the other tests).

CRITERIA FOR THE DIFFERENT SUBTYPES

• Amnestic single domain MCI: Impaired performance on tests of episodic memory.
• Amnestic multi-domain MCI: Impaired performance on test of at least one cognitive domain in addition to episodic memory.
• Non-amnestic single-domain MCI: Impaired performance in only one cognitive domain except episodic memory.
• Non-amnestic multi-domain MCI: Impaired performances in at least two non-memory cognitive domains.
• Subjective cognitive decline (SCD): No significant impairment in any test.

FOLLOW-UP FOR 8 YEARS

Every 12 months for up to 6 years full clinical, cognitive, neurological, and psychiatric evaluation are performed. CSF/blood collection and MRI are performed every 24 months. Year 8 and year 10 only full clinical, cognitive, neurological, and psychiatric evaluation are performed.

Dementia

ENROLLMENT

The dementia cohort have, between 2010 and 2015, consecutively included 300 patients diagnosed with dementia after a thorough clinical investigation at the Memory Clinic, Skåne University Hospital, Sweden. The cohort prospectively includes dementia patients with Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), frontotemporal dementia (FTD) or other dementias as well as 50 patients with familial Alzheimer’s disease.

INCLUSION CRITERIA

• Fulfills the criteria of dementia due to either Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, Parkinson’s disease with dementia or frontotemporal dementia.

EXCLUSION CRITERIA

• Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
• Current significant alcohol or substance misuse.

FOLLOW-UP FOR 6 YEARS

Participants are followed with repeated clinical and cognitive assessments every 12 months for at least 3 years to determine disease progression rate and clinical phenotype.

Parkinsonian disorders

ENROLLMENT

The study prospectively includes 400 patients since 2008 with parkinsonian symptoms, including de novo subjects, from the Neurology clinic at the Skåne University Hospital in Lund, Sweden.

INCLUSION CRITERIA

• Fulfills the criteria of Parkinson’s disease, Parkinson’s disease with dementia, progressive supranuclear palsy or multiple system atrophy. De novo patents with early parkinsonian symptoms are also included.

EXCLUSION CRITERIA

• Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
• Current significant alcohol or substance misuse.

FOLLOW-UP FOR 2 YEARS

Every 12 months for up to 4 years full clinical, cognitive, neurological, and psychiatric evaluation are performed. CSF/blood collection and MRI are performed every 24 months. Thereafter full clinical, cognitive, neurological, and psychiatric evaluation as well as CSF/blood collection are performed every 24 months up to year 10.

Table Healthy elderly

* A subset of participants performs [18F]Flutemetamol PET or [18F]AV1451-PET at one or repeated times during follow-up.  p.r.n.: pro re nata, when needed.

Table Mild cognitive complaints

* A subset of participants performs [18F]Flutemetamol PET or [18F]AV1451-PET at one or repeated times during follow-up. ** Derived from the Neuropsychological Assessment at some visits

Table Dementia

p.r.n.: pro re nata, when needed.

Table Parkinsonian disorders