# The precuneus and posterior cingulate gyrus support temporal orientation in Alzheimer’s disease

## TL;DR

This study shows that Alzheimer's disease affects the brain's ability to understand time, with changes in blood flow in specific brain regions linked to this decline.

## Contribution

The study identifies the bilateral pericallosal region as critical for temporal orientation in Alzheimer's disease.

## Key findings

- Healthy participants could distinguish past, present, and future, while those with AD and MCI showed impaired temporal orientation.
- Cerebral blood flow in the bilateral pericallosal region predicted cluster membership with 75% accuracy.
- Most AD participants belonged to a cluster with the poorest temporal orientation performance.

## Abstract

Although the classifications of ‘past,’ ‘present,’ and ‘future’ are considered abstract concepts, we naturally understand them. Those classifications were named ‘A-series’ time by McTaggart in 1908. Alzheimer's disease (AD) is the most common type of dementia, with initial symptoms generally including temporal disorientation. This study aims to (1) elucidate the impairment process of temporal cognition in AD by administering A-series temporal tasks to individuals with AD, mild cognitive impairment (MCI), and healthy controls, and (2) clarify the relationship between temporal cognition at each stage of impairment and cerebral blood flow (CBF). A diagnosis of AD (n = 37), MCI (n = 10), and no dementia (ND) (n = 10) took part. The ‘A-series’ task consisted of eleven short sentences that were grammatically correct using seven-time qualifiers (last week, yesterday, today, now, tomorrow, this week, or next week). The participants were required to respond when the events in the sentences happened or would happen in nine stages. We compared the pattern of their responses, the scores of the Japanese version of the Mini-Mental State Examination (MMSE-J), and the regional CBFs performed by 99mTc-ethyl cysteinate dimer Single Photon Emission Computed Tomography. We found that ND was intact in the ability to distinguish between the past, present, and future, on the other hand, AD and MCI showed a diminished ability in temporal orientation when we sorted the 11 sentences in the ascending order of the mean response scores among the ND participants, they were generally ordered according to the time represented by adverbs of time. We also found that the participants could be best classified into three clusters. All ND participants (10/10) and half of the MCI participants (5/10) belonged to Cluster 1, whereas only 19% of the AD participants belonged to the cluster (7/37). Cluster 2 was contributed by three MCI participants (3/10) and 30% of the AD participants (11/37). Finally, most of the AD participants (51%) belonged to cluster 3 (19/37) with a few MCI participants (2/10). We compared CBFs across the three clusters and found the CBF in the pairs of the left and the right pericallosal region could predict whether a participant belonged to either cluster at the largest hit rate of 75%. Our findings suggest that the bilateral pericallosal region, including the posterior cingulate gyrus and precuneus cortex, is associated with temporal orientation.

Futamura et al. report that the progression of temporal cognitive dysfunction in Alzheimer’s disease is associated with cerebral blood flow in the bilateral pericallosal regions, as measured by responses to verbal tense and temporal adverb stimuli.

Graphical Abstract