Right prosubiculum amyloid plaque density correlates with anosognosia in Alzheimer's disease.
BACKGROUND
Anosognosia is a common manifestation of Alzheimer's disease. There is an association between impaired awareness and frontal-executive cognitive deficits. Anosognosia is also correlated with decreased metabolism in the right hemisphere, particularly in frontal lobe regions.


OBJECTIVE
To investigate pathological correlates of anosognosia in Alzheimer's disease.


METHODS
41 subjects followed longitudinally in the University of Pittsburgh memory disorders clinic and with necropsy verified Alzheimer's disease were divided into two groups, based on previous clinical assessment: +Aware (n = 23) and -Aware (n = 18). A subset analysis matching subjects for dementia severity using mini-mental state examination scores was also carried out (13 +Aware; 13 -Aware). Histopathological data from necropsy brain tissue consisted of senile plaque (SP) and neurofibrillary tangle (NFT) counts (regional density) from four different brain regions in the right and left hemispheres: superior and middle frontal gyri (SMF), superior temporal isocortex (ST), the prosubiculum of the hippocampus (PRO), and the entorhinal cortex (EC).


RESULTS
SP density was greater in the right PRO region of -Aware subjects (F = 6.54, p = 0.015) than +Aware subjects. Significant differences between SP or NFT density were not observed in any other regions. In the subset analysis matching for dementia severity, SP density was again greater in the right PRO region of -Aware subjects than in the other regions (F = 12.72, p = 0.002).


CONCLUSIONS
Increased SP density in the right PRO region suggests that selective pathological involvement of this area contributes to awareness deficits in Alzheimer's disease. The putative role of the PRO in self appraisal may reflect its interconnections with other medial temporal and prefrontal regions.
Marshall
G A
GA
Department of Neurology, University of Pittsburgh, Pennsylvania, USA.
Kaufer
D I
DI
Lopez
O L
OL
Rao
G R
GR
Hamilton
R L
RL
DeKosky
S T
ST
D000368:Aged; D000377:Agnosia / Q000209:etiology*; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009460:Neurologic Examination; D010465:Perception; D058225:Plaque, Amyloid / Q000473:pathology*