Psychiatric Symptoms in Alzheimer’s Disease

Summary: Like cognitive deficits, psychiatric symptoms such as depression, apathy, and anxiety associated with Alzheimer’s disease appear to be a direct consequence of underlying brain changes as a result of increased amyloid-beta accumulation.

Source: Lund University

In addition to memory problems and other cognitive symptoms, most people with Alzheimer’s disease also suffer from mental health issues. It has long been unclear whether these occur because of tissue changes in the brain, or whether they represent psychological reactions to cognitive symptoms.

A study from Lund University in Sweden has provided new insight, and is published in Biological Psychiatry.

Cognitive symptoms combined with elevated levels of certain proteins form the basis for diagnosis of Alzheimer’s disease. At the same time, researchers and physician alike have, over the past decade, recognised that changes in mood and behaviour are often very early signs of the disease. Yet, these symptoms have not received as much scientific attention as cognitive ones. 

Now, researchers from Lund University have investigated the complex relationships between psychological symptoms, Alzheimer’s proteins and cognitive symptoms. This was done within the framework of the internationally renowned BioFINDER study, led by Professor Oskar Hansson. 

The study examined 356 people over the age of 65 with no cognitive symptoms at the start of the research. In addition to analysing the levels of the Alzheimer’s proteins amyloid beta and phosphorylated tau in their cerebrospinal fluid, participants’ levels of anxiety, apathy and overall cognitive function were also assessed on a biannual basis. Participants were followed for a total of eight years. 

When data was analyzed, the researchers found a clear link between elevated levels of amyloid beta at the start of the study and future development of anxiety and apathy. 

Maurits Johansson, physician and lead author of the study, explains: “Alzheimer’s disease affects large parts of the brain, including the regions that control our emotional life. Our study shows that psychiatric symptoms, just like cognitive symptoms, occur mainly as a direct consequence of the underlying changes to the brain, due to increased levels of amyloid beta.”

The researchers further demonstrated that amyloid beta drives the development of apathy predominately through direct effects, and that apathy only to a limited extent evolves secondary to cognitive decline.  Anxiety was not linked to cognitive change. 

This shows an older lady crying on a train
When data was analyzed, the researchers found a clear link between elevated levels of amyloid beta at the start of the study and future development of anxiety and apathy. Image is in the public domain

“The findings thus argue against the idea that these early changes in emotion and motivation in Alzheimer’s disease are primarily psychological reactions to cognitive decline. Instead, the results suggest that for apathy and anxiety at least, these occur due to the pathological accumulation of amyloid beta,” clarifies Professor Oskar Hansson.

“Our findings imply that psychiatric symptoms in Alzheimer’s disease could be used as alternative outcome measures in treatment trials. Ultimately, this could lead to more effective study design,” he continues.  

“A previous BioFINDER study suggested that the presence of anxiety or apathy among elderly people who continued to show no signs of dementia may point to an increased risk of future cognitive impairment.

“As a next step, studies are needed to clarify how these symptoms may contribute to the established clinical diagnosis in the early stages of disease, possibly even before cognition has been affected,” they conclude.

About this Alzheimer’s disease and psychiatry research news

Author: Lotte Billing
Source: Lund University
Contact: Lotte Billing – Lund University
Image: The image is in the public domain

Original Research: Open access.
Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer’s Disease Pathology and Cognitive Decline” by Maurits Johansson et al. Biological Psychiatry


Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer’s Disease Pathology and Cognitive Decline


The impact of Alzheimer’s disease (AD) pathology and cognitive deficits on longitudinal neuropsychiatric symptoms is unclear, especially in early disease stages.


Cognitively unimpaired older adults (N = 356) enrolled in the prospective Swedish BioFINDER study were examined. Neuropsychiatric assessments encompassed the Apathy Evaluation Scale and the Hospital Anxiety and Depression Scale, performed biennially (together with tests of global cognition) for up to 8 years. Biomarkers were measured in cerebrospinal fluid or plasma at baseline. Magnetic resonance imaging quantified white matter lesions. We used linear mixed-effect models to test associations between baseline AD biomarkers (for amyloid-β [Aβ], tau, and neurodegeneration) and white matter lesions with longitudinal neuropsychiatric symptoms (apathy, anxiety, and depressive symptoms). We also tested associations between changes in cognition and changes in neuropsychiatric symptoms. Finally, we tested if change in cognition mediated the effects of different brain pathologies on neuropsychiatric symptoms.


Aβ pathology at baseline was associated with increasing levels of apathy (β = −0.284, p = .005) and anxiety (β = −0.060, p = .011) longitudinally. More rapid decline of cognition over time was related to increasing levels of apathy. The effects of baseline Aβ pathology on longitudinal apathy were partly mediated by changes in cognitive performance (proportion mediated 23%).


Aβ pathology may drive the development of both apathy and anxiety in very early stages of AD, largely independent of cognitive change. The effect of Aβ on apathy is only partially conveyed by worse cognition. Together, these findings highlight certain neuropsychiatric symptoms as early manifestations of AD.

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