Circadian Rhythm Changes in Healthy Aging and Mild Cognitive Impairment

Abstract

Disruptions in circadian rhythms can occur in healthy aging; however, these changes are more severe and pervasive in individuals with age-related and neurodegenerative diseases, such as dementia. Circadian rhythm alterations are also present in preclinical stages of dementia, for example, in patients with mild cognitive impairments (MCI); thus, providing a unique window of opportunity for early intervention in neurodegenerative disorders. Nonetheless, there is a lack of studies examining the association between relevant changes in circadian rhythms and their relationship with cognitive dysfunctions in MCI individuals. In this review, circadian system alterations occurring in MCI patients are examined compared to healthy aging individuals while also considering their association with MCI neurocognitive alterations. The main findings are that abnormal circadian changes in rest-activity, core body temperature, melatonin, and cortisol rhythms appear in the MCI stage and that these circadian rhythm disruptions are associated with some of the neurocognitive deficits observed in MCI patients. In addition, preliminary evidence indicates that interventions aimed at restoring regular circadian rhythms may prevent or halt the progress of neurodegenerative diseases and mitigate their related cognitive impairments. Future longitudinal studies with repeated follow-up assessments are needed to establish the translational potential of these findings in clinical practice.

Keywords: circadian rhythm; mild cognitive impairment; neurocognitive function; older adults; young adults.

Figure 1.

A general illustration of circadian rhythms in young healthy, older healthy adults and MCI patients: a) presentation of different stages from young, healthy adulthood to dementia, with the gray-shaded triangle reflecting the progressive decrease in life expectancy across the lifespan; b) sketching of rest-activity rhythm in young, elderly, and MCI indicates: (1) a reduction in RAR amplitude in older adults compared to young subjects and of MCI individuals compared to both young and older adults, and (2) a RAR phase advance in older adults compared to young adults and MCI patients compared to other groups; c) sketching of core body temperature (CBT) changes in three groups depicts: (1) a lower peak-to-trough CBT amplitude in MCI compared to young and older healthy adults, (2) a decreased CBT amplitude of rhythm in older adults and MCI compared to young adults, and (3) a strong CBT phase advances in older adults compared to young adults; d) sketching of melatonin rhythm displays: (1) a decrease in melatonin with increasing age and in MCI compared to healthy groups, and (2) a phase advance in melatonin rhythm in older adults and MCI compared to young adults; e) sketching of cortisol rhythm changes in three groups shows: (1) elevation of morning cortisol in MCI patients compared to older and young healthy adults, and (2) phase advance in cortisol rhythm with increasing age. (Note: The X-axis and Y-axis values are on arbitrary units).

Figure 2.

Organization of human circadian rhythms. The superchiasmatic nucleus (SCN) is the master clock of the circadian rhythms. Photic Zeitgeber and non-photic Zeitgebers synchronize the SCN. All cerebral regions and peripheral tissues have their own internal clocks, where the final synchronization of the rhythms is regulated by SCN via humoral and neural connections.