Alzheimer’s Research & Therapy (Apr 2024)

Neuropsychiatric symptoms with focus on apathy and irritability in sporadic and hereditary cerebral amyloid angiopathy

  • Kanishk Kaushik,
  • Anna M. de Kort,
  • Rosemarie van Dort,
  • Reinier G.J. van der Zwet,
  • Bob Siegerink,
  • Sabine Voigt,
  • Erik W. van Zwet,
  • Maaike C. van der Plas,
  • Emma A. Koemans,
  • Ingeborg Rasing,
  • Roy P.C. Kessels,
  • Huub A.M. Middelkoop,
  • Floris H.B.M. Schreuder,
  • Catharina J.M. Klijn,
  • Marcel M. Verbeek,
  • Gisela M. Terwindt,
  • Ellis S. van Etten,
  • Marieke J.H. Wermer

DOI
https://doi.org/10.1186/s13195-024-01445-4
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 11

Abstract

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Abstract Background Neuropsychiatric symptoms (NPS) may affect cognition, but their burden in cerebral amyloid angiopathy (CAA), one of the main causes of intracerebral hemorrhage (ICH) and dementia in the elderly, remains unclear. We investigated NPS, with emphasis on apathy and irritability in sporadic (sCAA) and Dutch-type hereditary (D-)CAA. Methods We included patients with sCAA and (pre)symptomatic D-CAA, and controls from four prospective cohort studies. We assessed NPS per group, stratified for history of ICH, using the informant-based Neuropsychiatric Inventory (NPI-Q), Starkstein Apathy scale (SAS), and Irritability Scale. We modeled the association of NPS with disease status, executive function, processing speed, and CAA-burden score on MRI and investigated sex-differences. Results We included 181 participants: 82 with sCAA (mean[SD] age 72[6] years, 44% women, 28% previous ICH), 56 with D-CAA (52[11] years, 54% women, n = 31[55%] presymptomatic), and 43 controls (69[9] years, 44% women). The NPI-Q NPS-count differed between patients and controls (sCAA-ICH+:adj.β = 1.4[95%CI:0.6–2.3]; sCAA-ICH-:1.3[0.6-2.0]; symptomatic D-CAA:2.0[1.1–2.9]; presymptomatic D-CAA:1.2[0.1–2.2], control median:0[IQR:0–3]), but not between the different CAA-subgroups. Apathy and irritability were reported most frequently: n = 12[31%] sCAA, 19[37%] D-CAA had a high SAS-score; n = 12[29%] sCAA, 14[27%] D-CAA had a high Irritability Scale score. NPS-count was associated with decreased processing speed (adj.β=-0.6[95%CI:-0.8;-0.4]) and executive function (adj.β=-0.4[95%CI:-0.6;-0.1]), but not with radiological CAA-burden. Men had NPS more often than women. Discussion According to informants, one third to half of patients with CAA have NPS, mostly apathy, even in presymptomatic D-CAA and possibly with increased susceptibility in men. Neurologists should inform patients and caregivers of these disease consequences and treat or refer patients with NPS appropriately.

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