Box 2.

Late-onset Alzheimer Disease (Lo-AD)

Generals	– The most common cause of late-onset (≥ 65 yo) dementia [52]  – Incidence and prevalence increase with age (growing up because of an aging population) [1]  – Cerebrovascular disease frequently coexists with AD  – Cerebral amyloid angiopathy (CAA) can co-occur with AD  – General neurological examination is substantially normal  – Neuropsychiatric symptoms are common
Clinical features and diagnosis	Typical presentation:  – Early and prominent episodic memory loss (recent events) plus  – Executive, language, and visuospatial impairment	MRI  – Disproportionate bilateral (or mild asymmetric) temporoparietal cortical atrophy with (early) prevalent involvement of entorhinal cortex/ medial temporal lobes (± hippocampus ┼) and (more later) precuneus ¶ and posterior cingulate gyrus  – Relative sparing of the primary motor&somatosensory (pericentral) and occipital cortex FDG-PET: mirrors MRI findings, with gross correspondence between hypometabolic and atrophic areas Δ Ioflupane-SPECT (DaTscan): normal Amyloid-PET: abnormal diffuse cortex uptake with loss of gray-white differentiation (cerebellum spared) τ-PET: hippocampal-body and precuneus abnormal τ uptake in early-stage
	Atypical presentation/non-amnestic syndromes (more common in early-onset disease [42]):  – Visual variant—posterior cortical atrophy (PCA)  – Logopenic variant primary progressive aphasia (lvPPA)  – Progressive executive dysfunction		[For clinical overview and imaging findings see Box 3]
Pitfalls:  – Iron-sensitive sequences should be performed to assess for hemorrhages associated with CAA (see Box 9) [22]  - SVD associated WMHs frequent coexist with AD findings

┼ Compared to early-onset AD, patients with late-onset disease show greater medial temporal atrophy and less cortical atrophy

^¶ The involvement of precuneus is a late feature of lo-ad or an early feature of eo-AD [see Box 3]

Δ Usually the FDG-PET findings correspond to the MRI atrophic changes, but in some cases the molecular findings may be more severe than structural findings