Researchers at Inje University Ilsan Paik Hospital have discovered that neuropsychiatric symptoms such as delusions, anxiety, and apathy in Alzheimer's disease are connected to specific pathological protein accumulations in the brain. Led by Professor Lee Young-gun from the Department of Neurology, the team conducted the study using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
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ADNI is an international project that compiles brain imaging, clinical, and biomarker data to track the progression of Alzheimer’s disease and changes in biomarkers. The researchers analyzed brain imaging and clinical data from 336 individuals positive for amyloid-beta (Aβ), which included cognitively normal participants and those with mild cognitive impairment or early-stage dementia.
The analysis revealed that increased tau protein accumulation in the brain was linked to a higher incidence of symptoms such as delusions, agitation, irritability, and disturbances in eating or appetite. Region-specific assessments indicated that tau accumulation in regions like the temporal lobe, insula, and anterior cingulate cortex was particularly associated with delusions.
Additionally, the study considered the role of alpha-synuclein, a protein associated with Lewy body pathology. This analysis included 238 participants who underwent a cerebrospinal fluid alpha-synuclein seed amplification assay (SAA). Those with alpha-synuclein pathology exhibited significantly higher chances of experiencing delusions (5.52 times more likely), anxiety (2.25 times), apathy (3.45 times), and sleep disturbances (2.10 times). These associations remained significant even after adjusting for amyloid beta and tau levels.
The findings indicate that tau and Lewy body pathologies may exert different influences on neuropsychiatric symptoms in Alzheimer’s patients. Professor Lee emphasized the need to understand these behavioral and psychiatric symptoms in relation to brain pathology, rather than simply as consequences of cognitive decline. He called for further investigation to assess various biomarkers to improve the evaluation and management of symptoms in individual patients, particularly noting the possibility of Alzheimer's coexisting with other neurodegenerative conditions.
The study, titled "Effect of tau burden and Lewy pathology on neuropsychiatric symptoms in Aβ-positive individuals," was published in the most recent issue of the journal Alzheimer’s & Dementia.