Sleep in Frontotemporal Dementia is Equally or Possibly More Disrupted, and at an Earlier Stage, When Compared to Sleep in Alzheimer's Disease

Bonakis, Anastasios; Economou, Nicholas-Tiberio; Paparrigopoulos, Thomas; Bonanni, Enrica; Maestri, Michelangelo; Carnicelli, Luca; Coscio, Elisa Di; Ktonas, P.Y.; Vagiakis, Emmanοuil; Theodoropoulos, Panagiotis; Papageorgiou, Sokratis G.

doi:10.3233/jad-122014

Cited by 44 publications

(40 citation statements)

References 27 publications

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“…FTD, PSP, and AD patients all have decreased sleep and we have demonstrated that this phenotype is recapitulated in the P301S tauopathy mouse model . The progression of sleep disturbances over time has not been reported in tauopathy mouse models and we show here that sleep deficits worsen with age and disease progression.…”

Section: Discussionsupporting

confidence: 53%

“…Sleep disturbances are prevalent in tauopathies with up to 76% of FTD and 67% of AD patients exhibiting clinical sleep disturbances of some kind and as many as 20% of PSP patients displaying rapid eye movement (REM) sleep specific disorders . Although varied in presentation and pathology, tauopathies are associated with an overall decrease in sleep . Sleep disturbance is one of the leading causes of institutionalization in AD, however, the direct effect of tau pathology on sleep remains poorly understood …”

Section: Introductionmentioning

confidence: 99%

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Altered sleep and EEG power in the P301S Tau transgenic mouse model

Holth

Mahan

Robinson

et al. 2017

Ann Clin Transl Neurol

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ObjectiveSleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice.MethodsP301S and wild‐type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti‐phospho‐tau AT8 staining.ResultsP301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non‐REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation.InterpretationOur results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau‐induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Altered sleep and EEG power in the P301S Tau transgenic mouse model

Holth

Mahan

Robinson

et al. 2017

Ann Clin Transl Neurol

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“…Tau pathology is also likely to influence the sleep abnormalities observed in dementias since mouse models of such pathologies also show sleep disturbances not unlike those seen in AD models (Koss et al, 2016), and some tauopathies also elicit similar changes in sleep patterns (Bonakis et al, 2014). Sleep behaviour disorders are also an early feature of synucleinopathies (Högl, Stefani, & Videnovic, 2018).…”

Section: Sleep Amyloid Clearance and Neurodegenerationmentioning

confidence: 99%

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Nalivaeva

Turner

2019

British J Pharmacology

134

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Targeting the amyloid‐β (Aβ) peptide cascade has been at the heart of therapeutic developments in Alzheimer's disease (AD) research for more than 25 years, yet no successful drugs have reached the marketplace based on this hypothesis. Nevertheless, the genetic and other evidence remains strong, if not overwhelming, that Aβ is central to the disease process. Most attention has focused on the biosynthesis of Aβ from its precursor protein through the successive actions of the β‐ and γ‐secretases leading to the development of inhibitors of these membrane proteases. However, the levels of Aβ are maintained through a balance of its biosynthesis and clearance, which occurs both through further proteolysis by a family of amyloid‐degrading enzymes (ADEs) and by a variety of transport processes. The development of late‐onset AD appears to arise from a failure of these clearance mechanisms rather than by overproduction of the peptide. This review focuses on the nature of these clearance mechanisms, particularly the various proteases known to be involved, and their regulation and potential as therapeutic targets in AD drug development. The majority of the ADEs are zinc metalloproteases [e.g., the neprilysin (NEP) family, insulin‐degrading enzyme, and angiotensin converting enzymes (ACE)]. Strategies for up‐regulating the expression and activity of these enzymes, such as genetic, epigenetic, stem cell technology, and other pharmacological approaches, will be highlighted. Modifiable physiological mechanisms affecting the efficiency of Aβ clearance, including brain perfusion, obesity, diabetes, and sleep, will also be outlined. These new insights provide optimism for future therapeutic developments in AD research. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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“…associated with pervasive changes in behavior and personality. Characteristic changes include alterations in eating [3,4], emotion processing [5], and sleeping [6]. Disinhibition is commonly reported in the behavioral variant of FTD (bvFTD) [7] and has led to the assumption that bvFTD patients exhibit hypersexual behavior.…”

Section: Introductionmentioning

confidence: 99%

Characterizing Sexual Behavior in Frontotemporal Dementia

Kaizik

Irish

Mioshi

et al. 2015

JAD

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Abstract.Background: Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. Objective: We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer's disease (AD). Methods: Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. Results: BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90-100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Conclusion: Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus.

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Sleep in Frontotemporal Dementia is Equally or Possibly More Disrupted, and at an Earlier Stage, When Compared to Sleep in Alzheimer's Disease

Cited by 44 publications

References 27 publications

Altered sleep and EEG power in the P301S Tau transgenic mouse model

Altered sleep and EEG power in the P301S Tau transgenic mouse model

Targeting amyloid clearance in Alzheimer's disease as a therapeutic strategy

Characterizing Sexual Behavior in Frontotemporal Dementia

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