Positive family history of dementia (FH+) is a significant risk factor for clinical Alzheimer’s disease (AD), particularly
when there is a maternal history. Recent studies of clinically normal (CN) adult offspring have linked maternal history
of AD to reduced gray matter volume and FDG hypometabolism. However, little is known about the relationship of
family history to amyloid pathology, particularly in the absence of clinical symptomatology. We tested whether FH+
CN subjects had greater amyloid deposition and whether this was more evident in those with a maternal history.
We evaluated PiB PET data from a total of 58 CN (CDR 0) individuals (mean age 72±8) who stated that they knew
the cognitive status of their parents after the age of 63. Of these, 29 (mean age 70±7) reported they were FH+ and
29 (mean age 75±8) were FH-. Within the FH+ group, 21 subjects reported maternal histories of dementia (mFH+),
5 reported paternal histories (pFH+), and 3 reported dementia in both parents. We evaluated our hypothesis in 12
ROIs, covarying age.
Compared to FH-, FH+ subjects had greater cortical PiB retention in widespread frontal lateral, frontal, and parietal
ROIs (p<0.05). The subset of mFH+ subjects had increased PIB retention in frontal ROIs (p<0.05), whereas pFH+
did not differ from FH- CN. When the presence of the APOE4 allele was added to the model, the association of
PiB retention with mFH+ remained significant. (p<0.05).
Self-reported parental history of dementia is associated with increased amyloid deposition in clinically normal
individuals. The association appears to be driven by maternal history of dementia, and it is observed independently
of APOE status. These findings are consistent with the hypothesis that amyloid deposition occurs prior to any
clinical symptoms, and that family history is a significant risk factor for the development of AD pathology.