Neuropsychiatric and neural correlates of subjective cognitive complaint

Journal article

Background: Subjective cognitive complaint (SCC) has been reported in normal elderly (NE) and Mild Cognitive Impairment (MCI). Aims: We investigated the neuropsychiatric predictors of SCC in NE and MCI, and the biomarkers abnormalities, and neural correlates of SCC in MCI. Methods: Clinical, cognitive and imaging data of 233 MCI and 419 NE were obtained from the Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI-3) database. SCC was assessed by the Cognitive Change Index (CCI) and Everyday Cognition (ECog). Neuropsychiatric symptoms were evaluated through the Neuropsychiatric Inventory (NPI). Brain amyloid and tau status were obtained from [18 F]Florbetapir-PET and [18 F]Flortaucipir-PET SUVR in predefined target regions, and brain and grey matter volumes from structural MRI. Results: SCC was significantly correlated with depression, anxiety, apathy, irritability, and sleep disorders, in MCI. Linear regression showed that depression and anxiety were significantly associated to SCC index, in MCI. SCC was neither significantly different in amyloid positive vs. negative, nor in tau positive vs. negative MCI. MCI with SCC showed significantly lower Braak 3–4 region volume and reduced amygdala volume, compared to MCI without SCC. MCI with SCC and NPI showed lower posterior cingulate cortex volume compared to MCI without SCC or NPI, whereas MCI with SCC but without NPI had lower anterior cingulate cortex volume, compared to MCI without SCC or NPI. Conclusions: These findings recommend the crucial role of psychological therapies focused on anxiety and depression, to prevent the worsening of the subjective cognitive complaint that represent a strong factor of conversion to objective cognitive disorders.

Authors: De Lucia, N; Thayanandan, T; Palomba, S; Komici, K; Maldonato, NM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Aging Clinical and Experimental Research
• Volume: 38
• Issue: 1
• Article number: 123
• Publication date: 2026-03-23
• Acceptance date: 2026-03-11
• DOI: 10.1007/s40520-026-03378-4
• EISSN: 1720-8319
• ISSN: 1594-0667
• Language: English
• Keywords: Mild cognitive impairment; Depression; Subjective cognitive complaint; Anxiety; Brain amyloid