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Higher Rates of Sleep Transitions in Behavioral Variant Frontotemporal Dementia Reflects Imbalance in Sleep-Wake-Promoting Systems
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Key Takeaways
- Patients with bvFTD show increased sleep-wake transitions, indicating greater sleep instability compared to AD patients.
- Higher Insomnia Severity Index scores and poorer sleep quality were reported in bvFTD patients.
Compared with Alzheimer disease, those with behavioral variant FTD demonstrated increased light sleep (N1%) and reduced deep sleep (N3%), alongside altered sleep dynamics, such as higher transitions between N1 sleep and wake states.
Valentina Gnoni, PhD
A recently published study using patients with probable behavioral variant frontotemporal dementia (bvFTD) and age- and sex-matched probable patients with Alzheimer disease (AD) revealed that those with bvFTD had higher rates of transitions between wake and sleep than those with AD. Investigators concluded that increased sleep transitions in bvFTD suggest greater instability and may reveal imbalances in sleep-wake systems, offering insights into sleep alterations in these patients.
Led by Valentina Gnoni, a neurologist and neurophysiopathologist at the Center for Neurodegenerative Diseases and Aging Brain, the analysis included 18 patients with probable bvFTD (mean age, 70.11 [±8.23] years) and 18 age- and sex-matched probable patients with AD who underwent polysomnography (PSG) and completed sleep disorders questionnaires. Between the 2 groups, those with bvFTD had higher Insomnia Severity Index (ISI) scores and reported poorer sleep quality than those with AD (P <.01).
The study aimed to evaluate nocturnal sleep stage sequences and transitions in patients with bvFTD and AD, hypothesizing that bvFTD would demonstrate a distinct pattern of sleep stage organization, including increased transitions compared to AD. Additionally, the study authors explored whether EEG spectral features could differentiate bvFTD from AD and examined the relationship between sleep stage transitions and self-reported sleep disturbances in bvFTD patients.
In terms of sleep macrostructure, those with bvFTD exhibited higher N1% (Mann-Whitney U = 227; P <.05) and lower N3% (Mann-Whitney U = 96; P <.05) compared with the AD group. In addition, this group had a lower number of N3 shifts (Mann-Whitney U = 53.5; P <.001), a higher transitions between wake and sleep (tWS) index (Mann-Whitney U = 244; P <.01), and a higher transitions between N1 sleep and wake (tN1-W) index (Mann-Whitney U = 232; P <.05) compared with patients with AD. In bvFTD patients, correlation analysis revealed that age was negatively associated with tW-N1-N2-N3-REM (rs = −0.53, p < 0.05) and tN1-N2-N3-REM (rs = −0.56, P < 0.01), while ISI scores were positively correlated with tWS (rs = 0.51, P < 0.05).
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"This study offers evidence that sleep is more disrupted and unstable in bvFTD compared to AD and the altered sleep stage transition rates may reflect the subjective experience of poor sleep quality reported by patients with bvFTD,” Gnoni et al wrote. “It is plausible that the pathological changes affecting sleep–wake-promoting systems, and their connections with more anterior brain areas in bvFTD as compared to AD, may underlie these observed differences. The role of the orexinergic system cannot be ruled out and deserves deeper investigations."
Significant differences in spectral power were observed between patients with bvFTD and AD, with bvFTD patients showing higher sigma power during N1 (P < 0.05), N2 (P < 0.005), N3 (P < 0.05), and REM sleep (P < 0.01). Similarly, patients with bvFTD exhibited greater beta power in N2 (P < 0.05) and REM sleep (P < 0.01), as well as increased alpha power during REM sleep (P < 0.05). No significant group differences were found for slow oscillation, delta, or theta rhythms.
Investigators noted that a significant finding from the study was the positive association between ISI scores and transitions between wake and sleep, which was observed exclusively in patients with bvFTD.
Gnoni et al wrote, "Accordingly, it is, therefore, possible to speculate that insomnia complaints in bvFTD are not the result of alterations in standard sleep macrostructure metrics but instead originate from disruptions in state transitions, particularly in the mechanisms regulating the transition between wakefulness and sleep. These hypotheses are supported by the results of correlation analysis between tWS and the individual ISI items, which showed that tWS is positively associated with the scores of ISI items reflecting difficulties in sleep maintenance, while no association emerged with items reflecting difficulty falling asleep or early morning awakening."
