Overview of baseline assessments

Area Test / Scale Baseline
Biosamples CSF X
Plasma/serum X
Clinical impact of BBMs Assessment of diagnosis, management and treatment before and after BBM and CSF results X
Executive function and attention
TMT B (If MMSE>19) X
Memory ADAS-cog 10-word free immediate and delayed recall and recognition X
Recall of Picture Test X
Verbal ability
Letter S fluency X
Animal fluency X
BNT 15 (Mack ver 4) X
Global cognition MMSE X
MoCA x
RBANS (complete battery) X
Digital In-house developed tablet battery (BioCog) X
Mezurio Gallery Game and Tilt Task X
Digital Clock Test X
Speech recognition testing (ki elements) x
Cognitive and ADL questionnaires BAS+ X
Amsterdam iADL x
Cognitive reserve CRI-q X
Sleep RBD X
Quality of Life DemQoL X

B.   Clinical Evaluation and Cognition

Assessment of the clinical impact of using blood-based biomarkers (BBMs)

Primary Care Physicians

We document detailed information on diagnosis, certainty of diagnosis, patient management plans (including additional examinations, referrals, etc.), and changes in treatment after each step in the diagnostic process. The steps are as follows: step-1: care-as-usual without AD biomarkers; step-2: addition of plasma AD biomarkers; and step-3: addition of advanced work-up using a CSF/PET AD biomarker. Step 1-2 is performed by primary care physicians and step 1-3 by dementia experts at the memory clinic (as part of the reference standard). Through this process, we determine how the implementation of plasma biomarkers might improve diagnosis and management when no other AD biomarker is available, and also whether the results from plasma AD biomarkers yield diagnostic accuracy, certainty of diagnosis, and patient care that are comparable to more expensive and invasive CSF/PET biomarkers.

Cognitive testing

The cognitive battery is outlined in the table above. These include tradition and novel pen and paper tests, iPad tests, smartphone-based tests for homebased testing and the use of a digital pen. All cognitive tests (except for the RBANS battery) are performed blinded to the dementia experts at the memory clinic (reference standard) to avoid circular reasoning.

Assessments of symptoms and ADL

Cognitive symptoms

All subjects rate their memory and attention/executive function relative to others of the same age according to the Brief Anosognosia Scale (BAS). We have also added similar questions to cover the other cognitive domains. These questions have been validated against neuropsychological testing but there are data indicating that self-reported cognitive complaints are only valid in a lesser degree of cognitive impairment. Cognitive and associated symptoms are assessed using the Cognitive Impairment Questionnaire (CIMP-QUEST), filled out by an informant. Both participants and informant fill out the Cognitive Function Index (CFI).

Functional ability

This is evaluated with the informant-based Functional Activities Questionnaire (FAQ) focusing on instrumental activities of daily living (IADL). In addition, the digital Amsterdam iADL scale is filled out by an informant (results blinded to the dementia experts).

Global function

Participants are classified as having SCD, MCI or dementia based on the neuropsychological battery, clinical symptoms and loss of independence in ADL. In addition, the Clinical Dementia Rating (CDR) is performed by the dementia experts as part of the reference standard.

Depression and anxiety

Mood and anxiety levels are assessed using the Hospital Anxiety and Depression Scale (HADS).


The presence of REM sleep behavior disorder will be evaluated with a single validated composite question derived from the Mayo Sleep Questionnaire. Sleep quality is also assessed using questions from the Sleep Scale from the Medical Outcomes Study (MOS).

Cognitive reserve

Premorbid cognition and cognitive reserve are estimated using the Cognitive Reserve Index questionnaire (CRI-q), specifically the subitems “Education” and “Working Activity” (excluding “Leisure Time”).

Quality of Life

Quality of Life is assessed using both participant and informant-based ratings on the DemQoL scale.

C.  Cerebrospinal fluid (CSF) and blood sampling and analyzes

Lumbar CSF samples are collected according to a standardized protocol, adhering to the Alzheimer’s Association Flow Chart for CSF biomarkers. Lumbar punctures are performed between 8-12 am. 20 ml of CSF is collected in low binding tubes and stored on ice for 5-20 minutes before being centrifuged (2000g, +4°C, 10 min). Subsequently, the CSF is aliquoted in approximately 1 ml portions into low binding polypropylene tubes and then stored at -80°C until batch analyses.

About 0.5 ml of CSF from each individual at both baseline and follow-up is analyzed directly as part of routine clinical measurements for Aβ42, Aβ40, Tau, P-tau, and NfL using Lumipulse.

Plasma is collected two times, at the primary care unit and during the same visit as the lumbar puncture at the memory clinic. Blood is drawn into tubes containing either EDTA or Lithium heparin. Following centrifugation (2000g, +4°C, 10 min), plasma samples are aliquoted into low binding tubes and stored at -80°C pending biochemical analyses. Plasma from primary care is sent bi-weekly to C2N Diagnostics for analysis using the PrecivityAD2 test (mass spectrometry analysis of plasma Aβ42, Aβ40, p-tau217 and non p-tau217).

D.  Amyloid PET

For participant the do not undergo lumbar puncture, either unwilling to do so or because of contraindications, 18F-flutemetamole PET is performed to determine presence of amyloid pathology. All scans are assessed visually according to a standardized protocol.

E.    Enrollment in BioFINDER-2

After the baseline assessments, a subsample of participants are enrolled in BioFINDER-2 undergoing BioFINDER-2 baseline assessments and longitudinal follow-ups as described here.