Characteristics of Neural Network Changes in Normal Aging and Early Dementia

Hirohisa Watanabe; Epifanio Bagarinao; Satoshi Maesawa; Kazuhiro Hara; Kazuya Kawabata; Aya Ogura; Reiko Ohdake; Sayuri Shima; Yasuaki Mizutani; Akihiro Ueda; Mizuki Ito; Masahisa Katsuno; Gen Sobue

doi:10.3389/fnagi.2021.747359

Characteristics of Neural Network Changes in Normal Aging and Early Dementia

Front Aging Neurosci. 2021 Nov 22:13:747359. doi: 10.3389/fnagi.2021.747359. eCollection 2021.

Authors

Hirohisa Watanabe^{1

2}, Epifanio Bagarinao^{2

3}, Satoshi Maesawa^{2

4}, Kazuhiro Hara⁵, Kazuya Kawabata⁵, Aya Ogura⁵, Reiko Ohdake^{1

2}, Sayuri Shima¹, Yasuaki Mizutani¹, Akihiro Ueda¹, Mizuki Ito¹, Masahisa Katsuno⁵, Gen Sobue^{2

6}

Affiliations

¹ Department of Neurology, Fujita Health University, Toyoake, Japan.
² Brain and Mind Research Center, Nagoya University, Nagoya, Japan.
³ Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁶ Aichi Medical University, Nagakute, Japan.

Abstract

To understand the mechanisms underlying preserved and impaired cognitive function in healthy aging and dementia, respectively, the spatial relationships of brain networks and mechanisms of their resilience should be understood. The hub regions of the brain, such as the multisensory integration and default mode networks, are critical for within- and between-network communication, remain well-preserved during aging, and play an essential role in compensatory processes. On the other hand, these brain hubs are the preferred sites for lesions in neurodegenerative dementias, such as Alzheimer's disease. Disrupted primary information processing networks, such as the auditory, visual, and sensorimotor networks, may lead to overactivity of the multisensory integration networks and accumulation of pathological proteins that cause dementia. At the cellular level, the brain hub regions contain many synapses and require a large amount of energy. These regions are rich in ATP-related gene expression and had high glucose metabolism as demonstrated on positron emission tomography (PET). Importantly, the number and function of mitochondria, which are the center of ATP production, decline by about 8% every 10 years. Dementia patients often have dysfunction of the ubiquitin-proteasome and autophagy-lysosome systems, which require large amounts of ATP. If there is low energy supply but the demand is high, the risk of disease can be high. Imbalance between energy supply and demand may cause accumulation of pathological proteins and play an important role in the development of dementia. This energy imbalance may explain why brain hub regions are vulnerable to damage in different dementias. Here, we review (1) the characteristics of gray matter network, white matter network, and resting state functional network changes related to resilience in healthy aging, (2) the mode of resting state functional network disruption in neurodegenerative dementia, and (3) the cellular mechanisms associated with the disruption.

Keywords: MRI; aging; anatomical networks; dementia; energy failure; network hub; resting state network (RSN).

Publication types

Review