Cerebrospinal Fluid Biomarkers for Alzheimer Disease Among Patients With Dementia

The defining pathological features of Alzheimer disease (AD) may also be contributing factors in other dementias.

To examine the prevalence of β-amyloid (Aβ) and tau pathophysiological changes as indicated by cerebrospinal fluid biomarkers, as well as their association with clinical disease progression, across a broad range of dementias.

In this cross-sectional study with a duration of 12 years (October 5, 2010, to August 31, 2022), clinical data from the Swedish registry for cognitive disorders and dementia (SveDem) were merged with clinical routine biomarker measurements of the core cerebrospinal fluid biomarkers of AD: Aβ1-42, total tau (t-tau), and phosphorylated tau 181 (p-tau181). Participants were individuals with a dementia diagnosis who had a complete set of cerebrospinal fluid Aβ1-42, t-tau, and p-tau measurements registered less than 3 years after the date of diagnosis. Data were analyzed from April to November 2023.

Age, sex, and dementia diagnosis.

Biomarker profiles in relation to diagnosis and cognitive status as indicated by Mini-Mental State Examination (MMSE) scores.

Among 15 004 individuals with a dementia diagnosis in the SveDem database, 13 882 were included in this study (7328 females [53%], 6554 males [47%]; median [IQR] age, 74 [68-79] years). Apart from the AD groups (early-onset AD, 1150 [68%]; late-onset AD, 3392 [65%]; mixed AD and vascular dementia, 1038 [52%]), the dementia not otherwise specified group had the most patients (443 [25%]) with a clear AD-like biomarker profile, while Parkinson disease dementia and the frontotemporal dementia groups had the smallest shares (15 [9%] and 51 [8%], respectively). MMSE score was associated with cerebrospinal fluid Aβ1-42 in late-onset AD, vascular dementia, frontotemporal dementia, and dementia not otherwise specified; with t-tau in late-onset AD, early-onset AD, and dementia not otherwise specified; and with p-tau181 in early-onset AD.

Aβ-related pathology is a defining feature of AD, and most patients clinically diagnosed with AD have biomarker evidence of this process, but the same is found in other dementias, although less commonly. Cerebrospinal fluid biomarker concentrations of AD-like pathology were associated with cognitive function but mainly in patients with an AD-related diagnosis (early- and late-onset AD).