The Nature and Magnitude of Cognitive Impairment in Narcolepsy and Idiopathic Hypersomnia: A Meta-analysis
Paul Maruff1, Robert D. Latzman2, James Gattuso3, Giuseppe Plazzi4, Thomas E Scammell5, Brian Harel2
1Cogstate, 2Takeda Development Center Americas, Inc, 3The University of Melbourne, 4Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 5Department of Neurology, Beth Israel Deaconess Medical Center
Objective:
To quantify the nature and magnitude of cognitive impairment in narcolepsy and idiopathic hypersomnia (IH).
Background:
Narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and Idiopathic hypersomnia (IH) are rare central disorders of hypersomnolence with high disease burden, including cognitive complaints. Neuropsychological models provide a strong brain-behavior framework for identification of the nature and magnitude of cognitive impairment and integration into etiological models of NT1, NT2, and IH.
Design/Methods:
Following PRISMA guidelines, we performed a meta-analysis (MA) of neuropsychological studies of NT1, NT2 and IH conducted between 2000 and 2022. Each cognitive test comparing patient and control groups was classified by the neuropsychological domain it assessed. For each test, the difference between patient and control groups was expressed as a standardized mean difference (Cohen’s d). The MA estimated Cohen’s ds for cognitive domains pooled according to clinical disease group.
Results:
87 studies were identified and screened for inclusion; 39 satisfied inclusion criteria, yielding 35 comparisons (k): NT1: k=25; NT2: k=5; IH: k=5. Data were sufficient to compute pooled performance estimates for attention, executive function, and memory domains. The MA indicated impaired performance for all domains. For attention, a large magnitude impairment was found for NT1 (d=-0.90) and IH (d=-0.97), and moderate magnitude impairment for NT2 (d=-0.60). Moderate magnitudes of impairment were identified in executive function for NT1 (d=-0.30) and NT2 (d=-0.38), and in memory for NT1 (d=-0.33).
Conclusions:
The MA confirmed that cognitive impairments are present in NT1, NT2, and IH with impairment in the attention domain largest in each group. Moderate impairment was also found in executive function and memory. These results provide a quantitative confirmation of reports of cognitive difficulties made by patients and clinicians and provide a basis for the future design of studies to determine whether cognitive impairments can be ameliorated by treatments for narcolepsy and IH.