Neuropsychiatric Features in Patients With Idiopathic Normal Pressure Hydrocephalus: A Systematic Review and Meta-Analysis.

Purpose of Review: Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition characterized by impaired gait, cognition, and bladder function. Neuropsychiatric symptoms may be important in iNPH but are poorly understood. We report the first systematic review and meta-analysis estimating the prevalence, severity, and treatment responsiveness of neuropsychiatric symptoms and diagnoses in iNPH. We searched PubMed, CINAHL, Embase, Ovid, MEDLINE, Cochrane, and PsycINFO from inception until October 23, 2024, for peer-reviewed, original studies in adults with definite, probable, or possible iNPH that reported neuropsychiatric features using validated tools or clinician diagnosis (PROSPERO CRD42021287293). Case studies and series, as well as studies where diagnostic criteria for iNPH were unclear, were excluded. Study quality assessment and data extraction were independently performed by 2 authors, according to a proforma developed iteratively. Random-effects meta-analysis was used to pool proportions and standardized mean differences. Meta-regression, subgroup analysis, and sensitivity analysis were performed. Recent Findings: Twenty-two studies were included, of which 1 was a randomized-controlled trial. For our primary outcome, we found a high prevalence of apathy (69.2%, 95% CI 63.1-74.6, n = 293) and depression (30.1%, 20.1-42.3, n = 7,670) in iNPH. Agitation (22.6%, 11.8-39.1), anxiety (21.9%, 13.2-34.2), disinhibition (21.0%, 11.8-34.7), and psychotic syndromes (8.0%, 3.3-18.3) were relatively less prevalent. Depression scores were higher in patients with iNPH than in controls (Hedge's g 1.31, 0.39-2.23). Treatment of iNPH was associated with a reduction in depression scores (-0.30, -0.62 to 0.01), although the confidence interval contained the null. A total of 12 of 22 studies were rated 'low' quality. Summary: Apathy and depression are highly prevalent in iNPH, maybe more so than in other neurodegenerative conditions. Little is known about other neuropsychiatric features in iNPH. Treatment of iNPH may reduce neuropsychiatric symptoms, particularly depression. However, our study was limited by heterogeneity in populations and assessment tools and a lack of baseline data on neuropsychiatric symptoms before iNPH diagnosis. These findings highlight the urgent need for further research into neuropsychiatric features in iNPH, their mechanisms, and their potential response to treatment.