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J Neurol Neurosurg Psychiatry. 2004 October; 75(10): 1396–1400.
PMCID: PMC1738763

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.

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.

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Selected References

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  • Lopez OL, Becker JT, Somsak D, Dew MA, DeKosky ST. Awareness of cognitive deficits and anosognosia in probable Alzheimer's disease. Eur Neurol. 1994;34(5):277–282. [PubMed]
  • Michon A, Deweer B, Pillon B, Agid Y, Dubois B. Relation of anosognosia to frontal lobe dysfunction in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1994 Jul;57(7):805–809. [PMC free article] [PubMed]
  • Ott BR, Lafleche G, Whelihan WM, Buongiorno GW, Albert MS, Fogel BS. Impaired awareness of deficits in Alzheimer disease. Alzheimer Dis Assoc Disord. 1996 Summer;10(2):68–76. [PubMed]
  • Migliorelli R, Tesón A, Sabe L, Petracca G, Petracchi M, Leiguarda R, Starkstein SE. Anosognosia in Alzheimer's disease: a study of associated factors. J Neuropsychiatry Clin Neurosci. 1995 Summer;7(3):338–344. [PubMed]
  • Starkstein SE, Sabe L, Chemerinski E, Jason L, Leiguarda R. Two domains of anosognosia in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1996 Nov;61(5):485–490. [PMC free article] [PubMed]
  • Starkstein SE, Chemerinski E, Sabe L, Kuzis G, Petracca G, Tesón A, Leiguarda R. Prospective longitudinal study of depression and anosognosia in Alzheimer's disease. Br J Psychiatry. 1997 Jul;171:47–52. [PubMed]
  • Starkstein SE, Vázquez S, Migliorelli R, Tesón A, Sabe L, Leiguarda R. A single-photon emission computed tomographic study of anosognosia in Alzheimer's disease. Arch Neurol. 1995 Apr;52(4):415–420. [PubMed]
  • Reed BR, Jagust WJ, Coulter L. Anosognosia in Alzheimer's disease: relationships to depression, cognitive function, and cerebral perfusion. J Clin Exp Neuropsychol. 1993 Mar;15(2):231–244. [PubMed]
  • Ott BR, Noto RB, Fogel BS. Apathy and loss of insight in Alzheimer's disease: a SPECT imaging study. J Neuropsychiatry Clin Neurosci. 1996 Winter;8(1):41–46. [PubMed]
  • Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. [PubMed]
  • Moossy J, Zubenko GS, Martinez AJ, Rao GR. Bilateral symmetry of morphologic lesions in Alzheimer's disease. Arch Neurol. 1988 Mar;45(3):251–254. [PubMed]
  • Zubenko GS, Moossy J, Martinez AJ, Rao GR, Kopp U, Hanin I. A brain regional analysis of morphologic and cholinergic abnormalities in Alzheimer's disease. Arch Neurol. 1989 Jun;46(6):634–638. [PubMed]
  • Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. [PubMed]
  • Hyman BT, Van Hoesen GW, Damasio AR. Memory-related neural systems in Alzheimer's disease: an anatomic study. Neurology. 1990 Nov;40(11):1721–1730. [PubMed]
  • Turner BH, Knapp ME. Consciousness: a neurobiological approach. Integr Physiol Behav Sci. 1995 Apr-Jun;30(2):151–156. [PubMed]
  • Arikuni T, Sako H, Murata A. Ipsilateral connections of the anterior cingulate cortex with the frontal and medial temporal cortices in the macaque monkey. Neurosci Res. 1994 Nov;21(1):19–39. [PubMed]
  • Carter CS, Braver TS, Barch DM, Botvinick MM, Noll D, Cohen JD. Anterior cingulate cortex, error detection, and the online monitoring of performance. Science. 1998 May 1;280(5364):747–749. [PubMed]
  • Johnson Sterling C, Baxter Leslie C, Wilder Lana S, Pipe James G, Heiserman Joseph E, Prigatano George P. Neural correlates of self-reflection. Brain. 2002 Aug;125(Pt 8):1808–1814. [PubMed]
  • Frith Chris. Attention to action and awareness of other minds. Conscious Cogn. 2002 Dec;11(4):481–487. [PubMed]
  • Green RC, Mesulam MM. Acetylcholinesterase fiber staining in the human hippocampus and parahippocampal gyrus. J Comp Neurol. 1988 Jul 22;273(4):488–499. [PubMed]
  • Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999 Jun;22(6):273–280. [PubMed]
  • Kaufer Daniel I. Cholinesterase-inhibitor therapy for dementia: novel clinical substrates and mechanisms for treatment response. CNS Spectr. 2002 Oct;7(10):742–750. [PubMed]
  • Geula C. Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation. Neurology. 1998 Jul;51(1 Suppl 1):S18–S67. [PubMed]
  • Morris JC, Heyman A, Mohs RC, Hughes JP, van Belle G, Fillenbaum G, Mellits ED, Clark C. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989 Sep;39(9):1159–1165. [PubMed]
  • Santillan Concepcion E, Fritsch Thomas, Geldmacher David S. Development of a scale to predict decline in patients with mild Alzheimer's disease. J Am Geriatr Soc. 2003 Jan;51(1):91–95. [PubMed]
  • Derouesné C, Thibault S, Lagha-Pierucci S, Baudouin-Madec V, Ancri D, Lacomblez L. Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type. Int J Geriatr Psychiatry. 1999 Dec;14(12):1019–1030. [PubMed]

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