Skin Biopsy Diagnosis of Late-Onset Psychosis as Prodromal Dementia With Lewy Bodies: A Case Series.

OBJECTIVE

Severe psychiatric symptoms beginning in late life warrant evaluation for secondary causes, including neurodegenerative disorders. When neurodegenerative disorders manifest initially with isolated psychiatric features, they may be clinically indistinguishable from primary psychiatric illnesses such as late-onset schizophrenia. Accurate diagnosis is critical, especially for patients with underlying dementia with Lewy bodies (DLB), a synucleinopathy marked by early psychiatric symptoms, in particular psychosis, and extreme sensitivity to antipsychotic medications. Although clinically available biomarker tests are used in neurology to support the diagnosis of synucleinopathy, they have not been systematically applied in psychiatric populations.

METHODS

This case series describes five consecutive psychiatric inpatients (four with psychosis) who, over a 3-month period, received testing with a clinically approved skin biopsy to detect phosphorylated alpha-synuclein in cutaneous nerves as part of neurological and neuropsychiatric evaluations for late-onset severe psychiatric symptoms.

RESULTS

Two of the four patients with psychosis tested positive for synucleinopathy, and a third had multiple DLB features but tested negative. None of the patients met proposed clinical criteria for prodromal DLB, underscoring the need for updated criteria.

CONCLUSIONS

DLB may underlie a substantial proportion of late-onset psychosis. Clinically available biomarker tests, routinely used in neurology to diagnose DLB and other neurodegenerative disorders with motor or cognitive symptoms, can also identify these disorders when they begin with psychiatric symptoms. Prospective biomarker-based research is essential to improve recognition of psychiatric-onset DLB, refine diagnostic criteria, and guide appropriate treatment.