Brain atrophy subtypes are increasingly recognized in Alzheimer’s disease (AD) dementia. However, their relevance across the real-world memory clinic spectrum, from subjective cognitive impairment (SC Show more
Brain atrophy subtypes are increasingly recognized in Alzheimer’s disease (AD) dementia. However, their relevance across the real-world memory clinic spectrum, from subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) to AD and non-AD dementias, remains unclear. This cross-sectional study aimed to identify MRI-based atrophy subtypes in a relatively young memory clinic and examine associations with demographic, cerebrospinal fluid (CSF) biomarkers, and cerebrovascular burden to inform precision medicine approaches. We included all consecutive patients (SCI to dementia), evaluated at the Karolinska University-Hospital Memory Clinic (Stockholm, Sweden) between 2018 and 2023 with available clinical and 3T MRI data. Subtypes were defined using FreeSurfer-derived volumetric measures and a validated algorithm combining categorical classification (typical, limbic predominant, cortical predominant, minimal atrophy) with continuous indices of typicality (cortical predominant–limbic predominant) and severity (minimal atrophy–typical). Demographics, cognitive profiles, Among 809 patients (median age 60.0 years [interquartile-range 56.0–63.0], 56.1% female), 38.2% had SCI, 44.4% MCI, and 17.4% dementia. CSF biomarkers were available in 596 (73.7%). Limbic predominant and typical subtypes had more males (59.3% and 50.0%, respectively; group-wise p < 0.001), higher APOE ε4 frequency (47.7% and 41.0%, p = 0.02), greater cerebrovascular burden, and poorer memory. These subtypes were more often Aβ positive (46.1% and 46.5%, p = 0.01). A cortical predominant pattern was frequent in females (66.0%, p < 0.001), while minimal atrophy was associated with milder cognitive impairment (49.0% SCI, 45.5% MCI) and higher depressive symptoms. In Aβ-positive patients (n = 231), typical and limbic subtypes had higher p-tau181 (median: 83.0 and 84.5 pg/mL, respectively; p < 0.001), NFL (1120.0 and 1125.0 pg/mL, p < 0.001), and lower Aβ42/40 ratios (0.051 and 0.049, p = 0.02). Findings remained consistent across continuous atrophy measures and in the 14.9% (n = 89) eligible for anti-Aβ therapy. MRI-based atrophy subtypes exhibit distinct clinical and biomarker profiles, consistently observed in Aβ-positive and anti-Aβ-therapy-eligible patients. These findings support their diagnostic utility in memory clinics and relevance for biologically targeted AD trials. The online version contains supplementary material available at 10.1186/s13195-026-01972-2. Show less
Lecanemab and donanemab are the first anti-Aβ treatments to receive approval in Europe. Eligibility criteria are strict, eg., APOE ε4/4 carriers are excluded. Successful implementation in public healt Show more
Lecanemab and donanemab are the first anti-Aβ treatments to receive approval in Europe. Eligibility criteria are strict, eg., APOE ε4/4 carriers are excluded. Successful implementation in public healthcare hinges on accurate estimates of eligibility rates in settings which will be the first to roll out the treatments (specialized memory clinics with early disease stages). We applied the appropriate use recommendations (AUR) to assess treatment eligibility in a Swedish tertiary memory clinic where Aβ and APOE assessments are routinely performed. Of the full cohort (N = 410), 26 and 25 patients met the AUR criteria for lecanemab and donanemab, respectively (6 %; partial overlap between the groups). After excluding APOE ε4/4 carriers in line with the European guidelines, only 14 and 13 patients remained eligible (3 %). In clinics with younger populations, a significant percentage of potentially eligible patients are likely to have the APOE ε4/4 genotype. These findings are important to inform the implementation of anti-Aβ treatments. Show less