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

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.

Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease

“…Mormino and collaborators demonstrated a re-lationship between Aβ deposition (as measured with PIB imaging), hippocampal atrophy and episodic memory. They concluded that a decline in episodic memory in older individuals may be caused by Aβ 1−42 -induced hippocampus atrophy, with Aβ 1−42 deposition as the primary event in this cascade [50]. In line with this explanation, longitudinal hippocampal volume losses in individuals with MCI appear to be closely associated with a decrease in CSF Aβ 1−42 levels and increasing hyperphosphorylated tau [51].…”

Cortical phase changes in Alzheimer's disease at 7T MRI: A novel imaging marker

“…PET studies using PiB have shown the possibility of detecting cerebral amyloid accumulation, although the diagnostic utility is limited [47], and numbers on sensitivity and specificity are sparse. Mormino and colleagues [48] showed high sensitivity (90%) and specificity (90%) in differentiating AD patients from control subjects. However, within the group of healthy subjects, the specificity drops with increasing age, because the percentage of positive PiB-PET scans increases rapidly, with 12% of the people in their 60s, 30% in their 70s, and 50% in their 80s giving false-positive results [45,49,50].…”

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

“…Some remarkable works have resulted from this database, allowing to increase our understanding about the disease. For example, thanks to ADNI, it is currently known that AD starts to develop many years before symptoms are manifested [305,306], as well as the order in which biomarkers become abnormal [307,308] or the order in which atrophy of the brain occurs [309,310]. Identification of new biomarkers (in blood [311], ˛-Synuclein [312],.…”