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Timing of cognitive decline in CLN3 disease
Author(s) -
Kuper Willemijn F. E.,
Alfen Claudia,
Rigterink Roeliene H.,
Fuchs Sabine A.,
Genderen Maria M.,
Hasselt Peter M.
Publication year - 2018
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-018-0143-x
Subject(s) - cognitive decline , neurocognitive , pediatrics , cohort , cognition , medicine , psychology , disease , psychiatry , dementia
Background CLN3 disease is a major cause of childhood neurodegeneration. Onset of visual failure around 6 years of age is thought to precede cognitive deterioration by a few years, but casuistic reports question this paradigm. The aim of our study is to delineate timing of cognitive decline in CLN3 disease. Methods Early neurocognitive functioning in CLN3 disease was analyzed using age at onset of visual and cognitive decline and IQ scores from literature‐derived patient descriptions, supplemented with IQ scores and school history from a retrospective referral center cohort. We analyzed protracted and classical CLN3 separately and added a control group of patients diagnosed with juvenile onset macular degeneration (early onset Stargardt disease) to control for possible effects of rapid vision loss on neurocognitive functioning. Results Onset of cognitive decline at a mean age of 6.8 years (range 2–13 years, n = 19) paralleled onset of visual deterioration at a mean age of 6.4 years (range 4–9 years, n = 81) as supported by an early decline in IQ scores in classical CLN3 disease. Onset and course of vision loss was similar in patients with protracted CLN3. The decreased IQ levels at diagnosis (mean 68.4, range 57–79, n = 9) in the referral cohort were consistently associated with an aberrant early school history contrasting normal school history and cognition in Stargardt disease patients. Conclusions Cognitive dysfunction is universally present around diagnosis in classical CLN3 disease.