Short-Sleep Duration, Insomnia Linked to Doubled Risk for Cognitive Impairment

Julio J. Fernandez-Mendoza, PhD

Data from an analysis of the Penn State Adult Cohort suggest that insomnia accompanied by objective short sleep duration is linked to an increased prevalence of cognitive impairment, particularly as it relates to cardiometabolic health.¹

All told, those who reported poor sleep or chronic insomnia who slept for fewer than 6 hours were twice as likely to have cognitive impairment and possible vascular cognitive impairment compared with those who slept more than 6 hours. The analysis included 1524 adults (mean age, 48.9 years [±13.4]) and was conducted by Julio J. Fernandez-Mendoza, PhD, clinician scientist, Penn State Hershey Sleep Research & Treatment Center, Penn State Health, and colleagues.

“These data are among the first to indicate that patients who complain of insomnia and who sleep objectively short in the lab have a higher prevalence of mild cognitive impairment, particularly that associated with cardiometabolic risk factors,” Fernandez-Mendoza told NeurologyLive. “From a practice standpoint, patients with insomnia who have cardiometabolic risk factors should be objectively evaluated for their nighttime sleep and cognition, and not just evaluated by self-reports. Conversely, patients with mild cognitive impairment presenting at neurology clinics who complain of insomnia, should undergo a sleep study not only to examine the potential contribution of sleep apnea and other sleep disorders, but also to identify this more severe form of insomnia that may require specific treatment approaches.”

He added that from the treatment standpoint, the data imply these patients might require more targeted therapeutic approaches, such as a combination of cognitive-behavioral and pharmacological therapies, due to this “clustering of highly impairing conditions.”

For this analysis, self-reported sleep difficulty was defined as normal sleep (n = 899), poor sleep (n = 453), and chronic insomnia (n = 172). Objective short sleep duration was defined as less than 6 hours of sleep, which was based on in-lab, 8-hour polysomnography. Cognitive impairment (n = 155) and possible vascular cognitive impairment (n = 122) were determined with a comprehensive neuropsychological battery.

The odds ratios (ORs) for cognitive impairment for those with poor sleep and insomnia with objectively short sleep duration were 2.06 (95% CL, 1.15–3.66) and 2.18 (95% CL, 1.07–4.47), respectively. Likewise, the ORs for possible vascular cognitive impairment for those with poor sleep and insomnia who slept fewer than 6 hours were 1.94 (95% CL, 1.01–3.75) and 2.33 (95% CL, 1.07–5.06), respectively.

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In contrast, participants who slept objectively more than 6 hours did not have significantly increased odds of cognitive impairment when they reported either poor sleep (OR, 0.72; 95% CL, 0.30–1.76) or chronic insomnia (OR, 0.75; 95% CL, 0.21–2.71). Possible vascular cognitive impairment increased odds for those with poor sleep (OR, 1.08; 95% CL, 0.42–2.74) or insomnia (OR, 0.76; 95% CL, 0.16– 3.57) were also not significantly increased with more than 6 hours of sleep.

Furthermore, those who reported normal sleep and slept objectively less than 6 hours were also not associated with significantly increased odds of cognitive impairment (OR, 1.48; 95% CL, 0.86–2.55) or probable vascular cognitive impairment (OR, 1.23; 95% CL, 0.66–2.32) when compared with the reference group of participants who reported normal sleep and slept objectively more than 6 hours.

The association of insomnia with short sleep duration and cognitive impairment “is particularly strong for possible vascular cognitive impairment, as identified by the coexistence of cardiometabolic conditions and cognitive impairment in this study,” the investigators noted. They noted that a variety of literature point to the association of short-sleep insomnia with physiologic hyperarousal, including hyperactivity of the hypothalamic-pituitary-adrenal and sympatho-adrenal-medullary axes and impaired cardiac autonomic modulation, in addition to a greater risk of adverse cardiometabolic health outcomes.

Additionally, Fernandez-Mendoza et al. noted that 2 studies have shown that insomnia with objective short sleep duration is linked to altered brain-based biomarkers: glutamate metabolites and brain-derived neurotrophic factor.^2,3

“Taken together, these data can lead us to surmise that the etiology of cognitive impairment in middle-aged adults with insomnia with objective short sleep duration may be more likely related to dysfunction of the neurovascular unit and microvascular brain damage, such as asymptomatic deep brain infarction, white matter hyperintensities, and accelerated brain atrophy,” they wrote, noting that with older-adult-age follow-up, the cognitive impairment will likely ultimately result from a mixture of cerebral amyloid angiopathy and microinfarction, microhemorrhage, and macrohemorrhage, which typically underlie vascular pathology.

“We need longitudinal studies that follow large groups of good sleeping and poor sleeping young and middle-aged adults for enough years to ascertain whether insomnia with objective short sleep duration is a predictor of cognitive decline and future development of cognitive impairment and dementia,” Fernandez-Mendoz explained. “We also need these studies to include neuroimaging and biomarker data so that the underlying etiology of the cognitive impairment observed in individuals with this type of more biologically severe insomnia can be truly disentangled.”

REFERENCES
1. Fernandez-Mendoza J, He F, Puzino K, et al. Insomnia with objective short sleep duration is associated with cognitive impairment: a first look at cardiometabolic contributors to brain health. Sleep. Published online September 24, 2020. doi: 10.1093/sleep/zsaa150
2. Fan TT, Chen WH, Shi L, et al. Objective sleep duration is associated with cognitive deficits in primary insomnia: BDNF may play a role. Sleep. 2019; 42(1): doi: 10.1093/sleep/zsy192
3. Miller CB, Bartlett DJ, Mullins AE, et al. Clusters of insomnia disorder: an exploratory cluster analysis of objective sleep parameters reveals differences in neurocognitive functioning, quantitative EEG, and heart rate variability. Sleep. 2016;39(11):1993–2004. doi: 10.5665/sleep.6230