Box 3.

Early-onset Alzheimer Disease (Eo-AD: “not just an AD at a younger age”)

Generals	– The most common cause of early-onset (< 65 yo) neurodegenerative dementia [41] – AD with clinical onset younger than 65 yo – Better memory but worse attention/language/executive functions/visuospatial skills than Lo-AD
Clinical features and diagnosis	Up to two-thirds of patients with non-amnestic phenotypic variants:  – Logopenic variant primary progressive aphasia ┼ lvPPA (most common): progressive decline in language (word-finding difficulty with hesitations in repetition) with relatively spared memory and cognition  – Posterior cortical atrophy—PCA (second most common): progressive and disproportionate loss of visuospatial/visuoperceptual functions up to Gerstmann ¶ or Balint Δ syndrome  – Behavioral/dysexecutive (aka Frontal variant): early apathy/abulia or disinhibition and impulsivity  – Acalculia variant ◊ and other parietal syndromes (anomia, ideomotor apraxia, Gerstmann syndrome)  – Corticobasal syndrome (CBS) [see Box 7]	MRI:  – Hippocampal sparing and less mesial temporal lobe disease than Lo-AD  – Focal cortical atrophy  – Greater posterior (parietal, temporoparietal junction, posterior cingulate cortex) neocortical atrophy than Lo-AD  – Parieto-occipital and posterior temporal lobe involvement (PCA)  – Left posterior temporal cortex and the inferior parietal lobule involvement (lvPPA)  – Involvement of bilateral temporoparietal regions along with milder involvement in the frontal cortex (frontal variant)  – Biparietal involvement, greater on the left (parietal syndromes) FDG-PET: mirrors MRI findings, with gross correspondence between hypometabolic and atrophic areas Ioflupane-SPECT (DaTscan): normal Amyloid-PET: as in Lo-AD [see Box 2] τ-PET:  – Relatively distinct areas of uptake (tau uptake correlates with clinical symptoms [6, 79])  – Possible more uptake than Late-onset-AD due to increased Tau burden in posterior neocortices
Pitfall: if suspicious of PCA is clinically high, the absence of marked parieto-occipital atrophy should not exclude the diagnosis

┼ Other forms of PPA, such as the nonfluent/agrammatic and semantic variants, are non-Alzheimer syndromes due to FTLD [see Box 6]

^¶ Gerstmann syndrome: acalculia, left–right disorientation, finger agnosia, and agraphia

Δ Balint syndrome: ocular motor apraxia, optic ataxia, and simultanagnosia

◊ These patients overlap with or may eventually meet current criteria for posterior cortical atrophy or corticobasal syndrome