Major or Mild Frontotemporal Neurocognitive Disorder 617
left side usually being more affected. Nonfluent la nguage–variant major or mild fronto-
temporal NCD is associated with predominantly left posterior fr ontal-insular atrophy.
The logopenic variant of major or mild fron totemporal NCD is associated with predomi-
nantly left posterior perisylvian or parietal atrophy. Functional imaging demonstrates hy-
poperfusion and/or cortical hypometabolism in the corresponding brain regions, which
may be present in the early stages in the abse nce of structural abno rmality. Emerging bio-
markers for Alzheimer’s disease (e.g., cerebrospinal fluid amyl oid-beta and tau levels, and
amyloid imaging) may help in the differential  diagnosis, but the dist inction from Alzhei-
mer’s disease can remain difficult (the logopeni c variant is in fact often a manifestation of
Alzheimer’s disease).
In familial cases of frontotemporal NCD, the identification of genetic mutations may
help confirm the diagnosis. Mutations associated with frontote mporal NCD include
the genes encoding microtubule-associated protein tau (MAPT) and granulin (GRN),
C9ORF72, transactive response DNA-binding  protein of 43 kDa (TDP-43, or TARDBP),
valosin-containing protein (V CP), chromatin modifying protein 2B (CHMP2B), and fused
in sarcoma protein (FUS). 
Functional Consequences of Major or Mild 
Frontotemporal Neurocognitive Disorder
Because of the relative early age at onset of the disorder, the disorder oftens affects work-
place and family life. Because of the involvem ent of language and/or behavior, function is