The reliability and validity of DSM 5 diagnostic criteria for neurocognitive disorder and relationship with plasma neurofilament light in a down syndrome population

Abstract

The validity of dementia diagnostic criteria depends on their ability to distinguish dementia symptoms from pre-existing cognitive impairments. The study aimed to assess inter-rater reliability and concurrent validity of DSM-5 criteria for neurocognitive disorder in Down syndrome. The utility of mild neurocognitive disorder as a distinct diagnostic category, and the association between clinical symptoms and neurodegenerative changes represented by the plasma biomarker neurofilament light were also examined. 165 adults with Down syndrome were included. Two clinicians independently applied clinical judgement, DSM-IV, ICD-10 and DSM-5 criteria for dementia (or neurocognitive disorder) to each case. Inter-rater reliability and concurrent validity were analysed using the kappa statistic. Plasma neurofilament light concentrations were measured for 55 participants as a marker of neurodegeneration and between group comparisons calculated. All diagnostic criteria showed good inter-rater reliability apart from mild neurocognitive disorder which was moderate (k = 0.494). DSM- 5 criteria had substantial concurrence with clinical judgement (k = 0.855). When compared to the no neurocognitive disorder group, average neurofilament light concentrations were higher in both the mild and major neurocognitive disorder groups. DSM-5 neurocognitive disorder criteria can be used reliably in a Down syndrome population and has higher concurrence with clinical judgement than the older DSM-IV and ICD-10 criteria. Whilst the inter-rater reliability of the mild neurocognitive disorder criteria was modest, it does appear to identify people in an early stage of dementia with underlying neurodegenerative changes, represented by higher average NfL levels.

Blood Biomarkers for Alzheimer’s Disease in Down Syndrome

“…NfL levels were increased in individuals diagnosed with NCD compared with those without NCD, despite no significant age differences between groups. This study points to the potential synergistic role of NfL and clinical criteria in improving the dementia diagnostic procedure in DS [99].…”

Common mental health disorders and cognitive decline in a longitudinal Down syndrome cohort

“…Some of these challenges are related to difficulties with self-report of symptoms, diminished communication skills and differences in psychopathology presentation. 41 Others are driven by the reliance on data from informants who may have limited historical knowledge of an individual. 42 A significant consideration for clinicians is whether symptoms of cognitive decline in those with a history of mental health issues are related to a CMD rather than early symptoms of Alzheimer's disease.…”

Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome

“…While verbal fluency has been identified as a robust measure of cognitive decline and dementia onset in people with DS, the associations with the development of underlying neuropathology has not been established. Plasma biomarkers such as neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are associated with AD and show promise as diagnostic/prognostic biomarkers of AD in DS 22–26 . In DS, NfL levels have been found to be predictive of AD 26,27 and higher GFAP levels have been observed in response to abnormal brain amyloid beta (Aβ) accumulation 28 .…”

“…Plasma biomarkers such as neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are associated with AD and show promise as diagnostic/prognostic biomarkers of AD in DS. [22][23][24][25][26] In DS, NfL levels have been found to be predictive of AD 26,27 and higher GFAP levels have been observed in response to abnormal brain amyloid beta (Aβ) accumulation. 28 Determining the relationship between verbal fluency and these plasma biomarkers would help illustrate how this task reflects changes in underlying neuropathology.…”