Neuropsychiatric Symptoms in Alzheimer's Disease

Neuropsychiatric symptoms are common in Alzheimer’s disease, encompassing psychosis, agitation, apathy, depression and sleep disturbances. These manifestations often arise early in the disease course, predating marked cognitive deficits, and contribute substantially to caregiver burden and accelerated functional decline. Pathophysiological mechanisms involve distributed network dysfunction across frontal, limbic and subcortical regions, underpinned by synaptic loss, protein aggregation, neuroinflammation and small-vessel pathology. Different symptom clusters—such as delusions and hallucinations versus affective or apathetic presentations—reflect distinct circuit disruptions and molecular profiles. Recognising and characterising these symptoms is vital for prognostic stratification, personalised management and the development of targeted therapies.

Research from Nature Portfolio

Recent studies have identified alterations in the postsynaptic density proteome in individuals with Alzheimer’s disease who develop psychotic symptoms. Quantitative proteomic analyses of dorsolateral prefrontal cortex tissue revealed a broad reduction in synaptic proteins regulating cytoskeletal dynamics and kinase signalling. Computational drug-repurposing approaches predicted that inhibition of the chemokine receptor CCR5 could reverse these proteomic changes. Administration of a CCR5 antagonist in adult mice led to normalisation of synaptic protein levels, nominating this pathway as a promising target to alleviate psychosis in Alzheimer’s disease.

Neuropsychiatric Symptoms in Alzheimer's Disease publication trend

The graph below shows the total number of articles in neuropsychiatric symptoms in alzheimer's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Neuropsychiatric symptoms (NPS): Non-cognitive manifestations of Alzheimer’s disease, including psychosis, mood disturbances and behavioural changes.

Postsynaptic density (PSD) proteome: The collection of proteins located at the postsynaptic membrane critical for synaptic signalling and structural integrity.

White matter hyperintensities (WMH): Areas of increased signal on magnetic resonance images indicating small vessel disease and demyelination.

Cortical thickness: A measure of the thickness of the cerebral cortex, often used as an indicator of grey matter atrophy.

Behavioural and psychological symptoms of dementia (BPSD): A term encompassing the range of neuropsychiatric symptoms experienced by individuals with dementia.

References

1. Targeting the post-synaptic proteome has therapeutic potential for psychosis in Alzheimer Disease. Communications Biology (2023).
2. Unique transcriptional signatures correlate with behavioral and psychological symptom domains in Alzheimer’s disease. Translational Psychiatry (2024).
3. White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases. Alzheimer's Research & Therapy (2023).
4. Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort. Acta Neuropathologica Communications (2023).