Dataset Information

Diminution of context association memory structure in subjects with subjective cognitive decline.

ABSTRACT: Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.

SUBMITTER: Fan LY

PROVIDER: S-EPMC6866359 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Diminution of context association memory structure in subjects with subjective cognitive decline.

Fan Ling-Yun LY Lai Ya-Mei YM Chen Ta-Fu TF Hsu Yung-Chin YC Chen Pin-Yu PY Huang Kuo-Zhou KZ Cheng Ting-Wen TW Tseng Wen-Yi Isaac WI Hua Mau-Sun MS Chen Ya-Fang YF Chiu Ming-Jang MJ

Human brain mapping 20180308 6

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selecti ...[more]

PMID: 29516634

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Project description:Importance:The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical ?-amyloid [A?] and tau) provides an important opportunity to understand the basis of SCD and AD risk. Objective:To examine associations between SCD and global A? and tau burdens in regions of interest in clinically healthy older adults. Design, Setting, and Participants:This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for A?. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Main Outcomes and Measures:Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The A? level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of A?, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Results:Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high A? burden. Greater SCD was associated with increasing entorhinal cortical tau burden (??=?0.35; 95% CI, 0.19-.52; P?<?.001) and A? burden (??=?0.24; 95% CI, 0.08-.40; P?=?.005), but not inferior temporal tau burden (??=?0.10; 95% CI, -0.08 to 0.28; P?=?.27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for A? burden (??=?0.36; 95% CI, 0.15-.58; P?=?.001), and no interaction influenced SCD (??=?-0.36; 95% CI, -0.34 to 0.09; P?=?.25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Conclusions and Relevance:Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of A?. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

Dataset Information

Diminution of context association memory structure in subjects with subjective cognitive decline.

Publications

Diminution of context association memory structure in subjects with subjective cognitive decline.

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