Sietske Sikkes

DR., (Principal Investigator)


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    Personal profile

    Research interests

    My main mission is to find optimal measurement methods for cognition, everyday functioning and behavior in neurodegenerative disorders, both as early diagnostic markers and markers for disease progression.

    I’ve been making use of my background in clinical neuropsychology and epidemiology to study this in Alzheimer’s disease (AD)¸ which is characterized by cognitive decline and impairments in everyday functioning. My main research themes focus on (I) the early detection of functional and cognitive decline, (II) clinical outcome measures, (III) diversity in measurement and (IV) non-pharmacological interventions, with a focus on prevention. Breakthroughs in diagnosing AD based on biological characteristics, led to the possibility of diagnosing the disease before the onset of cognitive decline. In consequence, diagnosis and treatments are targeting these preclinical stages. 

    (I)                 Everyday functioning

    By performing a systematic review into instruments measuring everyday functioning, I demonstrated that existing tools were out-of-date, and had limited psychometric properties which would limit the ability to detect early functional changes. I then tackled this problem by developing the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire, a computerized and adaptive questionnaire. This questionnaire was developed with input from experts, clinicians, patients and their caregivers, to ensure content validity, and was then extensively psychometrically evaluated for optimizing  reliability and validity. Item Response Theory modeling was used to score the questionnaire, which allows taking into account that everyday activities differ in their cognitively complexity. The questionnaire is implemented in research studies worldwide, as well as in clinical trials and in clinical practice (>16 translations and cross-cultural adaptations). My future work targets making further use of algorithms for optimizing individualized measurements by computerized adaptive testing, and linking everyday functioning to biologically defined AD disease stages. By this work, I ultimately aim develop a functional biomarker.

    (II)               Cognition

    One of the key issues in addressing early AD disease stages, is tracking cognition. That is, how can we measure the clinical meaningfulness of a treatment when cognitive decline is not yet present? I targeted this key issue by studying the sensitivity of cognitive tests in detecting change over time in different preclinical AD disease stages, and by developing a composite measure of cognition and function: the cognitive-functional composite (CFC). This composite was tested in a prognostic cohort of patients with AD and mild cognitive impairment (MCI) and subjective cognitive decline, in one of the first studies providing a direct head-to-head comparison of several cognitive outcome measures in which we demonstrated the superiority of the CFC. The CFC is currently implemented in clinical trials as well as in clinical practice. My future work in cognition is targeting further improvement of cognitive measures by making use of novel assessment methods such as mobile phones, digital assessments and by making use of cognitive phenomena such as practice effects for the detection of early cognitive decline. The ultimate aim is to develop a cognitive biomarker.

    (III)             Subjective cognitive decline & behavior

    Subjective cognitive decline (SCD), that is experiencing cognitive decline in the absence of abnormal neuropsychological test scores, is increasingly recognized as an at-risk symptom for AD. In an international effort, we linked SCD to clinical progression to AD and other types of dementia, identified all measures used for the detection of SCD, identified main themes targeted and provided recommendations for the measurement of SCD. In a next step, we linked all SCD measurement items using item response theory, and I used this linked score to link SCD to biological characteristics of AD and clinical progression. In my collaboration with the Harvard Aging Brain Study, I linked individual SCD items to amyloid and tau in order to identify which complaints relate to AD. As SCD is closely linked to depressive symptoms, I also set up a study where we included depressive symptoms and looked at their link with AD characteristics. I also studied behavioral symptoms by translating the Mild Behavioral Inventory and by including this in the Catch-Cog study. My ultimate aim is to identify relevant cognitive complaints that relate to AD.

    (IV)             Diversity

    By studying IADL and cognition, looking at diversity is inevitable, as cultural differences influence which daily activities are performed. In my post-doctoral fellowship, I studies cross-cultural differences showing that those need to be taken into account when developing translations. As a results, I developed a cross-cultural validation procedure, which was used for the translation of the Amsterdam IADL Questionnaire. In a recent study, we studied item bias in everyday activities using differential item functioning. Despite differences in endorsement of activities, we found limited item bias. Another diversity theme is assessing sex differences, for which we initially studied sex differences in AD biomarkers. My future work is assessing diversity, cross-cultural and gender/sex differences within the cognitive and functional assessments, which the ultimate aim to provide valid measurements for all.

    (V)               Non-pharmacological interventions and prevention through lifestyle changes

    By optimizing the measurement of cognition and function, the next step is to improve cognition and function, in which I focus on non-pharmacological interventions. In an international effort, in my role as vice-chair of the non-pharmacological interventions professional interest area (NPI-PIA), we are conducting a scoping review of the entire field of non-pharmacological interventions, ranging from cognitive training, to reminiscence, music therapy, physical training and meditation. This work is proving that, despite its potential, the quality can be improved. Lifestyle is increasingly recognized to play an important role in AD and related disorders. In the EURO-SCD project (JPND) we demonstrated that there is a high need for brain health information in those with SCD, and that it is necessary to tailor lifestyle brain health information to contribute effectively to the prevention of dementia

    Education/Academic qualification

    PhD, Measuring IADL in dementia, VU University medical center

    Award Date: 14 Oct 2011

    External positions

    Assistant professor, VU University

    1 Aug 2019 → …

    research fellow, Massachusetts General Hospital/Harvard Medical School

    1 Dec 20171 Dec 2018


    • BF Psychology
    • Neuropsychology
    • HA Statistics
    • Psychometrics
    • RZ Other systems of medicine
    • Neurology

    Collaborations and top research areas from the last five years

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