S2.4 Alzheimer disease - new treatment strategies

Wednesday    16:45-18:00    S2.4         Auditoriet

Alzheimer disease - new treatment strategies

Chair: Bengt Winblad

Aims: This symposium contains four presentations covering recent findings regarding pharmacological treatment and preventive strategies.  Methods: New results from Nordic studies, literature reviews and new reports will be presented and future directions in the field discussed. Results: Dementia is a huge human, societal and economic burden worldwide. FINGER is the first large, multi-domain RCT indicating that prevention of cognitive decline may be possible. It has been challenging to find disease-modifying treatments for AD but new trial designs, better characterization of AD, and new treatments targets give reasons for optimism that new treatment and/or combinations of treatments may be achieved in the close future. Important is the diagnostic process to include well defined patients in future clinical trials. Conclusions: The Nordic countries are well placed to take the world lead in partnership with international organisations, to develop new approaches to prevent and effectively treat AD and other dementias and to provide models of compassionate care for patients and support for caregivers. Prevention and AD drug development should be a major public health priority where increased collaboration between academia, industry and policy makers is crucial.

S2.4.1 Comparison between new clinical and research diagnostic criteria in AD –

implications for our health care system and for inclusion in clinical trials

Tormod Fladby

University of Oslo, Norway

Background: To intervene in AD progression we need early identification of at-risk cases. Patients suffer long pre-dementia periods with increasing brain damage, but only criteria for the late stage mild cognitive impairment (MCI) are established. MCI is encompassed within the DSM-5 category “neurocognitive impairment”, with neither normal cognition, nor dementia. MCI is often preceded by subjective cognitive decline (SCD). MCI-AD is the earliest well-defined AD-stage, patients having biomarker changes consistent with AD neuropathology (amyloid plaques, Tau-containing neurofibrillary changes etc.). Criteria for earlier AD stages have been suggested e.g. employing combinations of biomarker changes (A/T/N, amyloid deposition (A), Tau-pathology (T), neuronal injury (N). We compare recruiting strategies for inclusion of cases with MCI-AD, and with A/T/N-category evidence of AD pathology, asking which is the best predictor for progression. Methods: We recruited cases to a Norwegian multi-center study, from either memory clinics or following advertisements and news broadcasts. Examinations included standardized CRFs, cognitive testing and laboratory protocols, cerebrospinal fluid A/T/N biomarkers and MRI. Results: 401 participants 40-80 years old were classified as controls (n = 102) or symptom cases, consisting of cases with SCD (n = 163) and MCI (n = 136). We compared cognition and A/T/N-classification in memory clinic-referrals (n = 86) to self-referred participants responding to advertisements and news bulletins (n = 179) at baseline and 2year follow-up. Both SCD and MCI cases had reduced cognition compared to controls. A/T/N classification according to recruiting category and available follow-up data will be presented. Conclusion: Results will be discussed related to diagnostic criteria and efficient recruiting of at-risk cases for AD progression.

S2.4.2 Innovative approaches in prevention trials for dementia and alzheimer: from

finger to world-wide fingers

Tiia Ngandu

            National Institute for Health and Welfare, Finland

Background: Prevention can be pivotal in halting the increase of dementia and Alzheimer´s disease (AD) cases. Given the multifactorial etiology of dementia and late-onset AD, multi-domain interventions targeting several vascular and lifestyle-related risk factors are most likely to be effective. Methods: Recent Nordic and international prevention trials will be presented. Results: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a pioneering trial providing the first evidence from large RCT that a multi-domain lifestyle intervention may prevent cognitive impairment. FINGER represents a successful pragmatic model, which is now being tested in diverse population-based settings (Europe, USA, China, Singapore, Australia). Novel approaches include combination of lifestyle intervention with pharmacological intervention (e.g. Multimodal preventive trials for AD) and use of modern technology (e.g. Healthy Aging Through Internet Counselling in the Elderly). To promote synergy across these studies and optimize efforts towards dementia prevention, we launched the World-Wide FINGERS network to share experiences and data, and plan joint initiatives. Conclusions: There is increasing evidence that it is possible to prevent or postpone the onset of late-life cognitive impairment and dementia with multi-domain lifestyle interventions. Tailored multimodal interventions combing non-pharmacological and pharmacological intervention are most likely to be most effective strategy to prevent AD dementia.

S2.4.3 Present and future treatment possibilities in alzheimer disease

Bengt Winblad

Karolinska institutet, Sweden

Background: In 2015, the number of people affected by dementia worldwide was estimated to almost 49 million, with an estimated cost of approx 818 bUSD. The prevalence of dementia is expected to reach 132 million in 2050, with an equivalent cost increase. So far, no cure or highly significant symptom relieving treatment is available. Methods: Increased understanding of the pathophysiology of Alzheimer disease (AD) has given us new therapeutic targets. Many clinical and experimental studies are ongoing, mainly based on anti-amyloid-β (Aβ) strategies, but the exact role played by Aβ in AD pathogenesis is not clear. Lately, also active immunotherapy studies on tau are introduced. Still, we need to acknowledge that a single cure for AD is unlikely to be found. Preclinical research is constantly providing us with new information of the complex AD puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Results: The last drug to enter the market place was in 2002. Since then, many products in different development phases have failed. Why? Wrong molecules, inappropriate animal models, inappropriate proof-of-concept studies, heterogeneous patient groups, too advanced disease, non-relevant outcome measures, between-center variability in increasingly globalised multi-center trials? Conclusion: Our hope for the future is not only to give the patient an early symptomatic relief but that new therapies could potentially slow or even halt the progression of the disease. Increased global collaboration between academia, industry and regulatory authorities is a vital step for a successful drug development.

S2.4.4 Treatment of behavioral and psychiatric symptoms in dementia

Knut Engedal

Norwegian National Advisory Unit on Ageing and Health, Oslo University Hospital, Norway

Background: The behavior of persons with dementia will change and many will have comorbid psychiatric disorders or psychiatric symptoms. Psychotropic drugs, which has limited effect and many side effects are too often used. This presentation will focus on effects and side effects of psychotropic drugs to people with dementia and discuss non-pharmacological treatments.

Methods: An unsystematic search in Medline was done and the results were compared with the recommendation in the Norwegian guidelines for dementia and own experiences. Results: The use of psychotropic drugs in Nordic nursing homes is frequent. The evidence of an effect of antidepressants is good if the person has dementia due to Alzheimer’s disease and if depression is severe. Otherwise the evidence is poor, and even not existent if antidepressants are used to treat behavioral symptoms. The evidence an effect of antipsychotics is poor and only existent in people have “real” psychotic symptoms, severe agitation and aggression. The risk for severe side effects is however large, both for typical and atypical antipsychotics, and only people with severe symptoms should be treated with such drugs and the treatment period should be short, less than 3 months. Individualized daily activities and person centered care are good alternatives to drug treatment and should be the first line treatment of behavioral problems in people with dementia living in nursing homes. Conclusions: Psychotropic drugs for behavioral and psychiatric symptoms in dementia should be limited to treatment of severe symptoms and the treatment period should be short.