heimer’s disease if they survive to midlife. Multiple vascular risk factors influence risk for
Alzheimer’s disease and may act by increasing  cerebrovascular pathology or also through
direct effects on Alzheimer pathology. 
Culture-Related Diagnostic Issues
Detection of an NCD may be more difficult in  cultural and socioeconomic settings where
memory loss is considered normal in old age, where older adults face fewer cognitive de-
mands in everyday life, or where very low educational levels pose greater challenges to
objective cognitive assessment.
Diagnostic Markers
Cortical atrophy, amyloid-predominant neuritic plaques, and tau-predominant neurofibril-
lary tangles are hallmarks of the pathological diagnosis of Alzheimer’s disease and may be
confirmed via postmortem histopathological examination. For early-onset cases with auto-
somal dominant inheritance, a mutation in on e of the known causative Alzheimer’s disease
genes—amyloid precursor protein (APP), presen ilin 1 (PSEN1), or presenilin 2 (PSEN2)—
may be involved, and genetic testing for such mutations is commercially available, at least
for PSEN1. Apolipoprotein E4 cannot serve as a diagnostic marker because it is only a risk
factor and neither necessary nor sufficient for disease occurrence.
Since amyloid beta-42 deposition in the br ain occurs early in the pathophysiological
cascade, amyloid-based diagnostic tests such  as amyloid imaging on brain positron emis-
sion tomography (PET) scans and reduced leve ls of amyloid beta-42 in the cerebrospinal
fluid (CSF) may have diagnostic value. Signs of neuronal injury, such as hippocampal and
temporoparietal cortical atrophy on a magnetic resonance image scan, temporoparietal