Neuroinflammation May Influence Neuropsychiatric Symptoms in Alzheimer Disease

Neuroinflammation associated with abnormal microglial activation was indicated as a potential biomarker for the development of neuropsychiatric symptoms (NPSs) in patients with Alzheimer disease (AD), according to a recent study published in JAMA Network Open.

Healthy vs Inflamed Brain Concept | image credit; gankevstock - stock.adobe.com

NPSs include nighttime disturbances, agitation, irritability, and more, and are very common in AD. Authors of the present study cited that NPSs occur in upwards of 60% of cases of AD. These symptoms can have serious consequences for these patients as they are linked to higher rates of mortality, hospitalization, caregiver distress, worse quality of life, earlier institutionalization, and increases in health care expenditure.

Previous research has associated NPSs with amyloid-β (Aβ) and tau pathologies, but there is increasing evidence suggesting that neuroinflammation could be an early contributor of this sort of disease progression. Microglial cells and astrocytes—which play a part in the brain’s immunity—could be responsible for an array of inflammatory responses that influence degrees of cognitive decline in patients with AD.

Furthermore, the current authors point to studies that suggest microglial activation highly correlated with the development of depression, anxiety, mania, and psychosis in a wide variety of psychiatric conditions. Yet, despite these connections, the relationship between microglial activation and NPS related to AD is an understudied subject. To address this knowledge gap, researchers conducted a study to investigate relationship between NPS and glial markers in patients with AD.

Data were collected from January to June 2023 for 109 individuals. Participants were recruited through the Translational Biomarkers in Aging and Dementia (TRIAD) cohort at McGill University in Canada. Of the 109, 39 were cognitively impaired (CI; 14 with AD and 25 with mild cognitive impairment [MCI]) and 70 were cognitively unimpaired (CU). Neuropsychological assessments were completed for all patients with the use of the Neuropsychiatric Inventory Questionnaire (NIP-Q), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR). Positron emission tomography (PET) was used to assess biomarkers of Aβ, tau, and microglial activation. Additionally, astrocyte reactivity was measured through plasma glial fibrillary acidic protein (GFAP).

Aβ-PET positivity was observed in 30% (n = 21) CU and 79% (n = 31) of CI individuals. NIP-Q severity cores (where higher scores indicate more severe symptoms) demonstrated that microglial activation was linked to the parietal, temporal, and frontal cortices (β = 7.37; 95%CI, 1.34-13.41; P = .01). Additionally, the researchers witnessed that the NPI-Q domain that was most closely related to microglial activation in the brain and subsequent NPSs was irritability (22.8%; β = 6.86; 95%CI, 1.77-11.95; P = .008), followed by nighttime disturbance (19.3%), agitation (14.1%), and then eating or appetite disturbances (12.4%). No significant associations were found between NPSs and astrocyte reactivity.

Researchers conclude by emphasizing the implications of their results and how they show that microglial activation could have damaging consequences on disease progression in patients with AD. As research and evidence grows in this area, this study suggests that identifying microglial activation biomarkers could be useful for pinpointing NPSs and, furthermore, that the development of drugs that target these biomarkers may mitigate the effects of NPSs on patients with AD.

Reference

Aguzzoli CS, Ferreira PCL, Povala G, et al. Neuropsychiatric symptoms and microglial activation in patients with Alzheimer disease. JAMA Netw Open. 2023 Nov 1;6(11):e2345175. doi:10.1001/jamanetworkopen.2023.45175