Episodic memory loss is related to hippocampal-mediated -amyloid deposition in elderly subjects

Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Brain (Impact Factor: 10.23). 12/2008; 132(Pt 5):1310-23. DOI: 10.1093/brain/awn320
Source: PubMed

ABSTRACT Although beta-amyloid (Abeta) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via 'Pittsburgh Compound-B' (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Abeta and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P < 0.0001), as well as between aHV and EM (P < 0.0001). When both aHV and PIB were included in the same model to predict EM, aHV remained significant (P = 0.0015) whereas PIB index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Abeta deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Abeta deposition as the primary event in this cascade. This pattern suggests that declining EM in older individuals may be caused by Abeta-induced hippocampus atrophy.

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Available from: Chester A Mathis, Aug 22, 2015
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    • "This finding is consistent with the early accumulation of tau-related pathology in the mesial temporal regions in AD compared to the relatively diffuse deposition of A␤ [7]. In a previous study, Mormino and colleagues reported that the relationship between cortical A␤ deposition and memory function was mediated by hippocampal volume [18]. Although a direct measure of tau-related pathology was not included in their study, the authors speculated that hippocampal volume might have acted as an indirect measure of NFT load. "
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    • "Decline in memory performance , particularly episodic memory, is a major characteristic of dementia, particularly in early-middle stages. However, it is also well established that there is normal aging-associated decline of episodic memory in the absence of dementia (Mormino et al., 2009). Therefore, with aging populations, it is not only important to investigate strategies to delay dementia onset, but also to increase resistance to aging-related cognitive decline. "
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    • "This cutoff is extrapolated from a previously validated PiB-PET SUVR cutoff of 1.47, by combined assessment of PiB-and AV45-PET in 21 ADNI subjects who underwent both types of amyloid-PET scanning. These methods are described in greater detail by the group (Jagust et al., 2009; Mormino et al., 2009) and on the ADNI web site (http://adni.loni. "
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