The association between sleep and Alzheimer's disease: a systematic review.

It is estimated that 45% of individuals with cognitive impairment experience sleep disturbances prior to the onset of cognitive symptoms. Assessing sleeping problems and enhancing sleep quality are critical first steps to reduce the risk of cognitive impairment. Objective: To review existing literature based on predefined eligibility criteria to understand the connection between sleep disturbance and Alzheimer's disease. Methods: A thorough and systematic evaluation of numerous studies was carried out to assess one or more of the following epidemiological factors: (1) sleep disorders, (2) cognitive impairment, and (3) risk estimates for cognitive impairment due to sleep. Results: Studies suggest that individuals who experience memory loss may encounter sleep disturbances before noticing other symptoms. Numerous sleep disorders, such as excessive and inadequate sleep duration, poor sleep quality, circadian rhythm abnormalities, insomnia, and obstructive sleep apnea were found to increase the risk of cognitive dysfunction and dementia. Additionally, lower sleep quality and shorter sleep duration have been linked to higher cerebral-ß-amyloid levels. Objective evidence for the development of cognitive impairment is provided by the architecture of sleep stages. Patients experiencing sleep problems may benefit from specific types of sleep medicine as a preventative measure against cognitive decline. Conclusion: Sleep disorders can have adverse effects on cognitive health. The duration and quality of sleep are fundamental factors for maintaining a healthy brain as we age. Proper sleep can aid prevent cognitive impairment, particularly Alzheimer's disease and dementia.

Acredita-se que 45% dos indivíduos com comprometimento cognitivo experimentem distúrbios do sono antes do início dos sintomas cognitivos. Avaliar problemas de sono e melhorar a qualidade do sono são passos críticos iniciais para reduzir o risco de comprometimento cognitivo. Objetivo: Revisar a literatura existente com base em critérios de elegibilidade predefinidos para entender a conexão entre distúrbios do sono e a Doença de Alzheimer. Métodos: Uma avaliação completa e sistemática de vários estudos foi realizada para avaliar um ou mais dos seguintes fatores epidemiológicos: (1) distúrbios do sono, (2) comprometimento cognitivo e (3) estimativas de risco de comprometimento cognitivo decorrente do sono. Resultados: Os estudos sugerem que indivíduos que experimentam perda de memória podem enfrentar distúrbios do sono antes de notarem outros sintomas. Foi constatado que vários distúrbios do sono, como duração excessiva e inadequada do sono, má qualidade do sono, anormalidades no ritmo circadiano, insônia e apneia obstrutiva do sono, podem aumentar o risco de disfunção cognitiva e demência. Além disso, menor qualidade do sono e duração mais curta do sono têm sido associadas a níveis mais altos de ß-amiloide cerebral. Evidências objetivas para o desenvolvimento de comprometimento cognitivo são fornecidas pela arquitetura dos estágios do sono. Pacientes que experimentam problemas de sono podem se beneficiar de tipos específicos de medicamentos para o sono como medida preventiva contra o declínio cognitivo. Conclusão: Os distúrbios do sono podem ter efeitos adversos na saúde cognitiva. A duração e a qualidade do sono são fatores fundamentais para manter um cérebro saudável à medida que envelhecemos. Um sono adequado pode ajudar a prevenir o comprometimento cognitivo, especialmente a Doença de Alzheimer e a demência.

Cerebrovascular disease in suspected non-Alzheimer's pathophysiology and cognitive decline over time.

BACKGROUND: The underlying cause of cognitive decline in individuals who are positive for biomarkers of neurodegeneration (N) but negative for biomarkers of amyloid-beta (A), designated as Suspected non-Alzheimer's pathophysiology (SNAP), remains unclear. We evaluate whether cerebrovascular disease (CeVD) is more prevalent in those with SNAP compared to A-N- and A+N+ individuals and whether CeVD is associated with cognitive decline over time in SNAP patients. METHODS: A total of 216 individuals from a prospective memory clinic cohort (mean [SD] age, 72.7 [7.3] years, 100 women [56.5%]) were included and were diagnosed as no cognitive impairment (NCI), cognitive impairment no dementia (CIND), Alzheimer's dementia (AD) or vascular dementia (VaD). All individuals underwent clinical evaluation and neuropsychological assessment annually for up to 5 years. Carbon 11-labeled Pittsburgh Compound B ([11 C]-PiB) or [18 F]-flutafuranol-positron emission spectrometry imaging was performed to ascertain amyloid-beta status. Magnetic resonance imaging was performed to assess neurodegeneration as measured by medial temporal atrophy ≥2, as well as significant CeVD (sCeVD) burden, defined by cortical infarct count ≥1, Fazekas score ≥2, lacune count ≥2 or cerebral microbleed count ≥2. RESULTS: Of the 216 individuals, 50 (23.1%) A-N+ were (SNAP), 93 (43.1%) A-N-, 36 (16.7%) A+N- and 37 (17.1%) A+N+. A+N+ individuals were significantly older, while A+N+ and SNAP individuals were more likely to have dementia. The SNAP group had a higher prevalence of sCeVD (90.0%) compared to A-N-. Moreover, SNAP individuals with sCeVD had significantly steeper decline in global cognition compared to A-N- over 5 years (p = 0.042). CONCLUSIONS: These findings suggest that CeVD is a contributing factor to cognitive decline in SNAP. Therefore, SNAP individuals should be carefully assessed and treated for CeVD.

The Association Between Standard Electrocardiography and Cerebral Small Vessel Disease in a Memory Clinic Study.

BACKGROUND: P-wave terminal force in lead V1 (PTFV1) on electrocardiography has been associated with atrial fibrillation and ischemic stroke. OBJECTIVE: To investigate whether PTFV1 is associated with cerebral small vessel disease (CSVD) markers and etiological subtypes of cognitive impairment and dementia. METHODS: Participants were recruited from ongoing memory clinic study between August 2010 to January 2019. All participants underwent physical and medical evaluation along with an electrocardiography and 3 T brain magnetic resonance imaging. Participants were classified as no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, and dementia subtypes (Alzheimer's disease and vascular dementia). Elevated PTFV1 was defined as > 4,000µV×ms and measured manually on ECG. RESULTS: Of 408 participants, 78 (19.1%) had elevated PTFV1 (37 women [47%]; mean [SD] age, 73.8 [7.2] years). The participants with elevated PTFV1 had higher burden of lacunes, cerebral microbleeds (CMB), and cortical microinfarcts. As for the CMB location, persons with strictly deep CMB and mixed CMB had significantly higher PTFV1 than those with no CMB (p = 0.005, p = 0.007). Regardless of adjustment for cardiovascular risk factors and/or heart diseases, elevated PTFV1 was significantly associated with presence of CMB (odds ratio, 2.26; 95% CI,1.33-3.91). CONCLUSION: Elevated PTFV1 was associated with CSVD, especially deep CMB. PTFV1 in vascular dementia was also higher compared to Alzheimer's disease. Thus, PTFV1 might be a potential surrogate marker of brain-heart connection and vascular brain damage.

Alzheimer's Disease THErapy With NEuroaid (ATHENE): A Randomized Double-Blind Delayed-Start Trial.

OBJECTIVES: Preclinical and clinical studies indicate a role for MLC901 (NeuroAiD II) in Alzheimer's disease (AD). The primary aim was to investigate its safety as add-on therapy to standard treatment and the secondary aims its effect on cognition and slowing disease progression. DESIGN: Randomized double-blind placebo-controlled delayed-start study. SETTING AND PARTICIPANT: Patients with mild to moderate probable AD by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n = 125), were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months when all patients received MLC901, in a delayed-start design (clinical trial registration: ClinicalTrials.gov, NCT03038035). METHODS: The primary outcome measure was occurrence of serious adverse events (SAEs) at 6 months. Secondary outcomes included the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and other assessment scales. RESULTS: There was no significant difference in the risk of SAEs between early and delayed starters at month (M) 6 (22.6% vs 27.0%, risk difference -4.4%, 90% CI -16.9% to 8.3%). Similarly, there was no significant difference in the risk of adverse events and the occurrence of stroke or vascular events between early and delayed starters throughout the 12-month study period. Early starters did not differ significantly on ADAS-Cog from delayed starters at M6 [mean difference (MD) -1.0, 95% CI -3.3 to 1.3] and M12 (MD -2.35, 95% CI -5.45 to 0.74) on intention-to-treat analysis. Other cognitive assessment scales did not show significant differences. CONCLUSIONS AND IMPLICATIONS: This study of 125 persons with dementia found no evidence of a significant increase in adverse events between MLC901 and placebo, thus providing support for further studies on both efficacy and safety. Analyses suggest the potential of MLC901 in slowing down AD progression, but this requires further confirmation in larger and longer studies using biomarkers for AD.