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Multidomain strategies to prevent cognitive decline and dementia should be efficiently targeted at different at-risk populations

Engaging in a multidomain lifestyle program prevents cognitive decline, and this type of an intervention benefits many older adults who are at increased risk of developing a dementing disorder, such as Alzheimer’s disease (AD). Once early clinical symptoms are already present, the risk of disease progression is increased regardless of the extent of AD-typical brain changes, according to the doctoral dissertation of Anna Rosenberg, MSc. The public examination can be followed online on Friday, October 23 2020 starting at 12 noon.

Dementia is an enormous global health challenge, and with no cure in sight, the current research focuses on developing strategies to prevent or delay its onset in at-risk individuals. In her thesis, Rosenberg used data from large, completed, pioneering randomized controlled dementia prevention trials as well as a memory clinic, with the aim to inform the future design and conduct of prevention trials. The aim was to investigate who the preventive strategies should ideally be directed at and who is most likely to benefit from them. By combining quantitative and qualitative methods, Rosenberg also studied older adults’ motivation and attitudes towards dementia prevention as well as their reasons to participate in a prevention trial.

In the Finnish landmark trial FINGER, a multidomain lifestyle intervention overall improved the cognitive performance of individuals with an increased risk of cognitive decline. Rosenberg found that the lifestyle program was effective irrespective of the participants’ sex, age, level of education, socioeconomic status, baseline cognitive performance, and vascular risk factors and risk profile. Cognitive benefits were evident in the entire study population, as opposed to being limited to certain subgroups of participants. The results indicate that the multidomain preventive strategies are effective, and they should be targeted specifically at those with an increased risk of cognitive decline. The results also support the implementation of the FINGER intervention in clinical practice.

With respect to early symptomatic AD, the current prevention trials often focus on individuals with clear AD-typical brain pathology, i.e., those with multiple abnormal AD-type biomarkers. The newer research diagnostic criteria for AD are strict and based on more invasive assessments, and it is increasingly difficult to identify and recruit suitable participants for trials. Rosenberg discovered in her thesis that the use of pragmatic and less restrictive criteria may be appropriate and preferred in certain prevention trials, as most individuals still meet the more restrictive criteria. In the multinational LipiDiDiet trial, participants were mainly recruited based on neuropsychological testing and a brain MRI scan due to feasibility reasons, and only a third of them underwent a lumbar puncture to measure the cerebrospinal fluid (CSF) biomarkers. When these samples were analyzed afterwards, the CSF biomarkers were often indicative of AD (e.g., the beta-amyloid (Aβ) levels were decreased). It is noteworthy that the disease progression appeared to be similar among those with multiple abnormal biomarkers as well as those with brain atrophy on MRI but unknown CSF biomarkers.

Another key finding in the dissertation was that AD cannot be definitely ruled out in early symptomatic individuals even if the CSF biomarkers are classified as normal. In a sample of Karolinska Institute memory clinic patients with CSF Aβ levels within the normal range based on the laboratory cut-offs, nearly 40% of the patients developed dementia, often the AD-type, within a fairly short follow-up period. Lower normal Aβ levels were associated with a higher dementia risk, suggesting that the classification based on sharp, dichotomous cut-off values is not an ideal strategy to assess and predict an individual’s risk of disease progression.

Willingness to help and personal benefits motivate older adults to participate in prevention trials

Using data from the multinational lifestyle-based prevention trial HATICE, Rosenberg also investigated older adults’ reasons to participate in prevention trials. Based on questionnaires and interviews with the study participants in Finland, France, and the Netherlands, the most important reasons for participation were a desire to contribute to science, the possibility to improve lifestyle, and access to additional medical monitoring. Medical monitoring was emphasized particularly in Finland where access to regular health care was perceived as limited. Individuals with a family history of dementia or other experiences with affected people were worried about their cognition and dementia risk but also motivated towards improving their lifestyles. Cognitive assessments and blood tests in HATICE were sometimes thought to facilitate the early detection of a dementing disorder. Knowledge about dementia and risk factors was limited overall, and dementia was often considered a part of normal aging. The results highlight the importance of increasing the public awareness of dementia and the means to reduce its risk. Better understanding of older adults’ motivations and expectations will help design even more effective interventions.

A lot of progress has been made in the dementia prevention research, but more knowledge is urgently needed about the most feasible and effective prevention strategies in different at-risk populations. The findings of this thesis are useful when planning new prevention trials. Such trials are currently ongoing or being planned around the world, for example within the World Wide FINGERS (WW-FINGERS) global network including already over 30 countries.

The doctoral dissertation of Anna Rosenberg, MSc, entitled Dementia prevention in at-risk individuals: Focus on selection and engagement of target populations, will be examined at the Faculty of Health Sciences on Friday, October 23 2020 starting at 12 noon. The opponent will be Professor John O’Brien, University of Cambridge, and the Custos will be Professor Miia Kivipelto, University of Eastern Finland and Karolinska Institute. The public examination will be held in English.

Rosenberg, Anna. Dementia prevention in at-risk individuals: Focus on selection and engagement of target populations

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