The Alzheimer’s Association International Conference (AAIC) 2014 took place in the wonderful city of Copenhagen, with the global Alzheimer’s research community converging to discuss the latest results and findings in the field, whilst determining our next steps on the path to discovering methods of treatment and prevention. On the Saturday, a preconference day was held, during which nine different Professional Interest Area groups, including Neuroimaging and Blood-based biomarkers, met to discuss emerging topics. The plenary session was given by Professor Philip Scheltens, who gave an enlightening talk on the progress made during the 10 years of the multicentre Alzheimer’s Disease Neuroimaging Initiative (ADNI).

The main conference began on the Sunday. Each day followed the same structure, with there being a morning session containing several parallel series of talks, before all attendees convened for the plenary session. Then after lunch, and a two hour poster session, two further sessions of parallel talks followed in the afternoon. The plenary session on Sunday was given by Professor Bruno Vellas, who discussed how best to optimise design of preventative drug trials in Alzheimer’s. Professor Vellas emphasised the importance of specific targeted intervention, with the best target likely to change depending on the stage of the disease. On the first evening of the conference a welcome reception was held at the delightful Tivoli Gardens, the world’s second oldest amusement park, where researchers were able to network and socialise in beautifully scenic surroundings, whilst also being able to enjoy the numerous fairground rides on offer.

Monday’s plenary session involved two talks; the first of which was given by Dr Francine Godstein, who discussed the potential benefits of nutritional intervention in reducing the incidence of dementia. Dr Wiesje van der Flier then gave an interesting talk on subjective cognitive decline and emerging evidence to support its value in predicting clinical progression, which was a theme that recurred several times during the conference.

On Tuesday Dr Kenneth Langa gave a thought-provoking talk on the epidemiology of Alzheimer’s; highlighting the fact that, with better treatment of vascular risk factors and improved education (which is thought to increase congnitive reserve), the age-specific risk of dementia in high income countries is now beginning to decline. However, the opposite is true in poorer countries, where increasingly unhealthy lifestyles are causing an increase in risk factors, particularly those relating to vascular disease. Therefore, with the over 65 population expected to more than double globally over the next 35 years, the projected cost of dementia care at a global level could treble by 2050. The second plenary talk on Tuesday was given by Professor Kari Stefansson, who prior to his talk was presented with the Inge Grundke-Iqbal Award for Alzheimer’s Research. Professor Stefansson gave a very engaging presentation, in which he discussed recent genetic advances in Alzheimer’s disease, including his own discovery of the protective A673T mutation in APP, which have given us further insight with regards to disease mechanisms.

A particular highlight of the parallel sessions on Wednesday morning was a series of talks on initial findings from Tau PET imaging, with results from several different PET tracers being discussed. This is an area that may have the potential to provide a sensitive and specific marker of early neurodegenerative change, and a potential trial endpoint, whilst at the same time improving our understanding of the disease’s natural history. The plenary talks on Wednesday included an update from Dr Rosa Rademakers on research relating to the C9ORF72 gene repeat expansion, which is now known to be the most common genetic cause of FTLD. There was also an informative talk on the clinical evolution of dementia with Lewy bodies form Dr Bradley Boeve. A further highlight, from Wednesday afternoon, was a talk given by Professor Keith Josephs, who presented evidence from a large series of post-mortem cases that suggests that TDP-43 deposition amplifies memory loss and hippocampal atrophy in Alzheimer’s, and also appears to be able to overpower what has been termed “resilient cognition” in AD. The results suggest therefore that TDP-43 may be a key player in the Alzheimer’s neurodegenerative process, in addition to A-beta amyloid and tau, and could potentially be a therapeutic target for the treatment of AD.

The conference concluded on Thursday, with two interesting talks on CSF A-beta amyloid accumulation and kinetics, firstly from Professor Colin Masters, followed by Professor Randall Bateman. It is hoped that improvements in understanding and measurement techniques relating to these parameters will lead to greater ability to detect the earliest molecular pathological changes, which can be utilised both for diagnosis and to measure efficacy of new anti-amyloid drugs.

Overall, almost 500 oral presentations and 1,500 poster presentations were given during the five day main conference, with a vast array of diverse areas covered. A key message throughout the conference was the importance of focusing our attention, in terms of both developing treatments and developing and refining novel biomarkers, to early in the disease process, ideally in the period before the onset of any progressive cognitive symptoms, when the minimum of irretrievable neuronal loss has occurred. Numerous oral sessions on therapeutic trials were held, focusing on both drug development and trial design; but a positive clinical trial outcome is as yet still elusive. A lot of work was presented that aimed to identify novel therapeutic targets, including increasing evidence of the important role of inflammatory pathways in the pathological process of AD. In terms of biomarkers, work investigating both neuroimaging and liquid (both CSF and blood-based) measures continues to advance. In particular, the conference contained a number of sessions devoted to combining imaging modalities, both molecular and structural, with CSF measures to achieve a more comprehensive and reliable understanding of an individual’s disease stage.

Research into dementia stands at the doorstep of major breakthroughs in the field, and whilst further work is clearly needed, the work presented at AAIC allows one to be optimistic that effective disease-modifying treatments can be found.

ACNR Published online 10/9/14