Disconnection of the right superior parietal lobule from the precuneus is associated with memory impairment in oldest-old Alzheimer's disease patients

Abstract

There is a wide range of onset age in Alzheimer's disease (AD). Emerging evidence indicates variation of AD manifestations in oldest-old AD (OOAD); however, the pattern of cognitive dysfunctions remains unclear. We aimed to reveal cognitive performance characteristics and changes in brain functional connectivity in OOAD patients by a resting-state fMRI (rs-fMRI) study. We enrolled AD patients who had been referred to Kyushu University Hospital (KUH) or Sanno Hospital, and classified them into middle-old AD (MOAD) (65–79 years old) and OOAD (≥80 years old) according to the age of onset. Our subjects consisted of 19 OOAD, 17 MOAD, and 8 normal subjects. Cognitive performance was evaluated using Mini Mental State Examination-Japanese (MMSE-J) and Clinical Dementia Rating (CDR). rs-fMRI scanning and independent component analysis (ICA) were performed on Sanno Hospital patients and MOAD vs. OOAD patients were compared. The resulting significant regions were used as seeds for ROI-to-ROI analysis of the KUH dataset. Collectively, MMSE-J delayed recall sub-scores were significantly lower in OOAD patients compared with MOAD patients. ICA of the Sanno Hospital data indicated significant connectivity decrease in the default mode network (DMN) in the OOAD group compared with the MOAD group in the right superior parietal lobule (SPL). ROI-to-ROI analysis of the KUH dataset indicated significant disconnection in the OOAD group of the right SPL from the precuneus (p < 0.01). The functional connectivity from the right SPL to the precuneus was positively correlated with the MMSE-J delayed recall sub-score (p = 0.03) and negatively correlated with the CDR memory sub-scale (p = 0.04). These findings indicate that disconnection between the right SPL and the precuneus may contribute to worse memory capability in OOAD compared with MOAD.

Bridging patterns of neurocognitive aging across the older adult lifespan

“…The cross-sectional study also found greater bilateral frontoparietal connectivity that predicted better visuospatial performance for the oldestold (Jiang et al, 2020), whereas the longitudinal study observed age-related increases in connectivity between the insula and supplementary motor area, with precuneus connectivity relating to changes in general cognitive performance (Li et al, 2020). Results of both studies were independent of whole brain volume and comparable to findings within younger-old and oldest-old adults with Alzheimer's disease (e.g., in the default mode network; Prawiroharjo et al, 2020), suggesting that they are not driven by cognitive dysfunction.…”

Bridging Patterns of Neurocognitive Aging Across the Older Adult Lifespan

“…The cross-sectional study also found age-related increases in bilateral frontoparietal connectivity that predicted better visuospatial performance for the oldest-old (Jiang et al, 2020), whereas the longitudinal study observed age-related increases in connectivity between the insula and supplementary motor area, with precuneus connectivity relating to general cognitive performance (Li et al, 2020). Results of both studies were independent of whole brain volume loss and comparable to findings within younger-old and oldest-old adults with Alzheimer's disease (e.g., in the default mode network; Prawiroharjo et al, 2020), suggesting that they reflect normal aging processes.…”

Cognitive Reserve Modulates Brain Structure and Cortical Architecture in the Alzheimer’s Disease

“…In particular, AD-HCR patients compared with AD-LCR showed reduced thickness in a cluster included the post-central gyrus (BA3), the precuneus (BA7) and the posterior cingulate cortex (BA31). The precuneus and the posterior cingulate cortex have been previously recognised as involved in memory functioning [48][49][50]. AD-HCR patients showed also thinner thickness in the BA44 (i.e., Broca's area), which is implicated in speech production.…”