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1 Department of Neurology, University of Pittsburgh and Pittsburgh VA Medical Center, Pittsburgh, Pennsylvania, USA
2 Department of Pathology (Neuropathology), University of Pittsburgh and Pittsburgh VA Medical Center
3 Alzheimer’s Disease Research Center, University of Pittsburgh and Pittsburgh VA Medical Center
4 Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USA
Correspondence to:
Correspondence to:
Dr D Kaufer
UNC School of Medicine, CB# 7025, 3114 Bioinformatics Bldg, Chapel Hill, NC 27599, USA; kauferd{at}glial.med.unc.edu
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.
Design: 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.
Keywords: Alzheimer’s disease; anosognosia; acetylcholine
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