A Systematic Review of Evidence for a Role of Rest-Activity Rhythms in Dementia

Abstract

Background: Rest-activity rhythm (RAR) disruption may be a risk factor for dementia that can be objectively measured with wearable accelerometers. It is possible that risk monitoring and preventive interventions could be developed targeting RARs. To evaluate whether current evidence supports these applications, we systematically reviewed published studies linking RARs with dementia, its course, and mechanisms.Methods: Entering pre-defined search terms in PsycINFO, MEDLINE, and PubMed databases returned 192 unique titles. We identified 32 articles that met our primary inclusion criteria, namely, that they examined objective RAR measures in the context of dementia, cognition, or brain biomarkers.Results: Cross-sectional studies consistently found that people with dementia had less stable (5/6 studies), more fragmented (4/6 studies), lower amplitude rhythms (5/5 studies), that had a worse fit to 24-h models (3/3 studies). Findings from studies relating RARs to cognitive test performance (rather than diagnostic status) were more nuanced. RAR fragmentation was associated with neurodegeneration biomarkers in 2/2 studies; and 1/1 study found 24-h model fit related to hippocampal hyperactivation. Although 2/2 studies found RARs related to markers of cerebrovascular disease, the specific RARs and cerebrovascular disease measures were not consistent. Longitudinal studies (3/3 articles) reported that lower amplitude and worse 24-h rhythm fit predicted future cognitive impairment and executive function. However, interventions aimed at modifying RARs had mixed effects (e.g., 0/4 studies demonstrated effects of morning light on 24-h model fit; evening light was associated with improved 24-h fit in 2/2 studies reporting); these effects may be more evident in subgroups.Conclusions: Consistent evidence shows that dementia is associated with disrupted RARs. Importantly, recent studies have shown that RAR disruption is associated with dementia biomarkers and, prospectively, with the risk of cognitive impairment. Interventions mostly tried using bright light to modify RARs in people who already have dementia; these studies produced modest effects on RARs and did not show modification of dementia’s course. Altogether, these findings suggest studies are needed to understand how RARs relate to changes in brain health earlier in the disease process. Better understanding of the biopsychosocial mechanisms linking RARs with future dementia risk can help further target intervention development.

Circadian Rhythms and Epilepsy: A Suitable Case for Absence Epilepsy

“…Circadian disruption caused by, for example, shift work can lead to adverse health consequences and increased risk of cancer, metabolic, neurodegenerative, cardiovascular, or mental diseases (16)(17)(18)(19). Very often deviations from well-established rhythmicity (e.g., mistimed episodes of sleep and wakefulness, lack of daily variation in blood pressure, so-called nondipping) are the first signs of serious pathological processes developing in organisms (20,21). On the other hand, if the acquired pathology regards a rhythmic process or a bodily system that is clearly regulated by the circadian timing system, then it can be expected that the symptoms would follow a circadian pattern as well.…”

24-h Activity Rhythms and Health in Older Adults

“…For example, nonparametric measures have been suggested to better reflect 24-h rhythms in elderly persons, because rhythms are generally less cosine shaped in older adults [12••]. In contrast, cosinor measures seem to be associated more consistently with outcomes such as cognitive functioning [14]. A description of the most commonly used cosinor and non-parametric estimates can be found in Table 1.…”

Associations of rest-activity patterns with amyloid burden, medial temporal lobe atrophy, and cognitive impairment

“…Evaluation of dementia patients requires not only cognitive and neurological examination, but also assessment of available disease biomarkers such as cortical amyloid burden. However, it is still unclear whether or not rest-activity pattern changes depend on the aetiology of neurodegeneration [14] .…”

“…Rest-activity pattern changes have been reported in numerous studies of patients with moderate to severe dementia, as reviewed in [14] . Decreased total activity, fragmented 24-h activity rhythm, blunted rhythm amplitude, and phase delay have been documented in these patients [15] , [16] , [17] , [18] , [19] .…”