Detection of Prodromal Alzheimer’s Disease in Patients with Depression and Mild Cognitive Impairment Using 11C-PIB PET: Preliminary Study
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Background: There is increasing evidence of an empirical link between late-life depression and cognitive impairment. Depressive symptoms may be the earliest identifiable clinical stage of dementia. In contrast, depression may represent an independent risk factor predisposing to dementia disorders, including Alzheimer’s disease (AD). Among individuals with amnestic mild cognitive impairment and depression (aMCID), it is largely unknown who has brain amyloid deposition and will progress to AD. We employed the amyloid PET imaging using 11C-Pittsburgh Compound B (11C-PiB) to determine the presence of AD pathology in patients with aMCID. We examined differences in the clinical or radiological features between subjects with aMCID with amyloid deposition and those without. Methods: Twelve patients with aMCID (10 multiple-domain aMCID, 2 single-domain aMCID) underwent 11C-PiB PET, brain MRI, and neuropsychological test. Depressive symptoms were measured with the Geriatric Depression Scale (GDS) and those with the GDS score being 18 and over were designated as aMCID. By calculating the mean cortical PiB uptake ratio, we divided patients with aMCID into PiB-positive and PiB-negative groups. Results: Eight (66.7%) of 12 patients with aMCID were positive for cortical PiB binding. There was a significant difference between PiB-positive and PiB-negative groups in terms of the apolipoprotein E (ApoE) ε4 allele frequency (100% vs. 0%, p=0.006) and GDS score (24.2 vs. 28.2, p=0.03). The neuropsychological assessment revealed that patients with 11C-PiB-negative aMCID performed better on the recognition of visual memory test than those with PiB-positive. Conclusions: In patients with aMCID, the presence of cortical amyloid was strongly associated with the APOE ε4 allele. This finding suggests that those with aMCID and ApoE4 genotype may be a prodromal state to AD.
Abstract
Background: There is increasing evidence of an empirical link between late-life depression and cognitive impairment. Depressive symptoms may be the earliest identifiable clinical stage of dementia. In contrast, depression may represent an independent risk factor predisposing to dementia disorders, including Alzheimer’s disease (AD). Among individuals with amnestic mild cognitive impairment and depression (aMCID), it is largely unknown who has brain amyloid deposition and will progress to AD. We employed the amyloid PET imaging using 11C-Pittsburgh Compound B (11C-PiB) to determine the presence of AD pathology in patients with aMCID. We examined differences in the clinical or radiological features between subjects with aMCID with amyloid deposition and those without. Methods: Twelve patients with aMCID (10 multiple-domain aMCID, 2 single-domain aMCID) underwent 11C-PiB PET, brain MRI, and neuropsychological test. Depressive symptoms were measured with the Geriatric Depression Scale (GDS) and those with the GDS score being 18 and over were designated as aMCID. By calculating the mean cortical PiB uptake ratio, we divided patients with aMCID into PiB-positive and PiB-negative groups. Results: Eight (66.7%) of 12 patients with aMCID were positive for cortical PiB binding. There was a significant difference between PiB-positive and PiB-negative groups in terms of the apolipoprotein E (ApoE) ε4 allele frequency (100% vs. 0%, p=0.006) and GDS score (24.2 vs. 28.2, p=0.03). The neuropsychological assessment revealed that patients with 11C-PiB-negative aMCID performed better on the recognition of visual memory test than those with PiB-positive. Conclusions: In patients with aMCID, the presence of cortical amyloid was strongly associated with the APOE ε4 allele. This finding suggests that those with aMCID and ApoE4 genotype may be a prodromal state to AD.
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