Neuropsychiatric Impairments and Neurotransmitter-related Functional Alterations in Alzheimer’s Disease

Depressed mood, agitation, false beliefs, lack of motivation and other alterations in behaviour, usually named with the umbrella term of neuropsychiatric symptoms (NPS), are commonly observed in people with Alzheimers disease (AD). NPS are highly prevalent in people with AD (35-85%) and increase the risk of dementia by up to 10 times. The onset of NPS may even precede that of cognitive deficits and predict subsequent cognitive decline. Although not all patients experience NPS and some experience only very mild symptoms, clarifying AD aetiology is of primary importance to improve early diagnosis, provide better care and mitigate the economic burden of dementia. The neural changes associated with NPS in AD are still unclear and, consequently, wide consensus on the best treatment strategies is lacking. Since the earliest accumulation of AD pathology is observed in the nuclei involved in the production of neurotransmitters, the NINFA-AD project aims to investigate whether alterations in brain functioning influenced by abnormalities in different neurotransmitter pathways may be associated with NPS in people either with or at risk for AD. This aim will be pursued by applying an innovative interdisciplinary approach combining functional magnetic resonance with positron emission tomography imaging, fluid AD biomarkers and cognitive data. The NINFA-AD project will provide novel hypothesis-based insights on the cause of these symptoms that will lead to more efficient treatments and improvements in patients' prognosis. Moreover, the findings could be exploited to develop more informative biomarkers to be used in trials to test the mechanisms of action and effectiveness of novel interventions targeting behavioural problems in AD.