Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts

Introduction Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach. Methods We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters. Results In each cohort, a two-clusters solution best fitted the data (cophenetic correlation >0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%–52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P <.05). Conclusions We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics

Hypometabolism of the posterior cingulate cortex is not restricted to Alzheimer's disease

When differential diagnosis of dementia includes both Alzheimer's disease (AD) and the behavioural variant of frontotemporal dementia (bvFTD), distribution of cerebral glucose metabolism as measured using [18F]‑2‑fluoro‑2‑deoxy‑D‑glucose positron emission tomography ([18F]FDG-PET) may be helpful. One important clue for differentiation is the presence of hypometabolism in the posterior cingulate cortex (PCC), usually associated with AD. PCC hypometabolism however, could also be present in bvFTD. Therefore, the specificity of PCC hypometabolism was examined. Based on visual reading PCC hypometabolism was present in 69–73/81 probable AD patients, in 10–16/33 probable bvFTD patients, and in 0–1/22 cognitive normal (CN) subjects. Findings were validated using a PCC to reference tissue [18F]FDG standard uptake value ratio (SUVr) cut-off, which was derived from the receiver operating characteristic (ROC) separating probable AD from CN, resulting in 9–14/33 bvFTD patients having PCC hypometabolism, depending on the reference tissue used. In conclusion, PCC hypometabolism is not restricted to AD