Integrated approaches to geriatric mental disorders: pathophysiology, interventions, and precision medicine horizons

The global aging demographic has precipitated a surge in late-life mental disorders (LMDs)-including late-life depression (LLD), anxiety, and behavioral and psychological symptoms of dementia (BPSD)-posing critical public health challenges. This review synthesizes current evidence on the unique pathophysiology, clinical management, and emerging frontiers of geriatric mental health, emphasizing the interplay of neurobiological aging, multimorbidity, and psychosocial stressors. Key pathophysiological mechanisms include "inflammaging" (microglial overactivation), cerebral small vessel disease (CSVD), and senescence of monoaminergic systems, which collectively reduce neural resilience and complicate diagnosis. Clinical challenges-such as atypical symptom presentation (e.g., somatic masking of depression), polypharmacy risks, and diagnostic ambiguity between LLD and pseudodementia-necessitate tailored interventions. Notably, caregiver burden represents an independent predictor of patient institutionalization. Multiple systematic reviews and meta-analyses have consistently identified caregiver burden and distress as significant predictors of nursing home admission, with carer stress sometimes serving as the single determining factor for this transition. This underscores the critical need to integrate caregiver well-being into routine clinical assessment. Pharmacological strategies prioritize SSRIs/SNRIs but require cautious dosing due to age-related pharmacokinetic alterations (e.g., reduced renal clearance) and cardiovascular/metabolic risks. Emerging targets (e.g., ketamine for treatment-resistant LLD, anti-inflammatory agents guided by biomarker profiling) highlight a shift toward precision. Psychotherapeutic adaptations-including modified cognitive behavioral therapy (CBT), problem-solving therapy (PST), and life review therapy-address cognitive and psychosocial needs, while integrated care models (e.g., Collaborative Care Model [CoCM]) demonstrate superior outcomes over fragmented care. Lifestyle interventions (exercise) and neuromodulation (rTMS) further expand treatment options. Critical gaps remain, including underrepresentation of older adults in clinical trials and pervasive polypharmacy. Future directions emphasize pharmacogenomics, AI-driven early detection, and culturally equitable care to advance precision psychiatry for LMDs. This synthesis provides clinicians and researchers with a roadmap to navigate the complexities of geriatric mental health, advocating for multidisciplinary, patient-centered approaches to improve outcomes in aging populations.