Advanced sleep phase syndrome: Role of genetics and aging.

Advanced sleep phase (ASP) is seldom brought to medical attention because many individuals easily adapt to their early chronotype, especially if it emerges before the age of 30 and is present in a first-degree relative. In this case, the disorder is considered familial (FASP) and is mostly discovered coincidentally in the presence of other sleep disorders, mainly obstructive sleep apnea syndrome (OSAS). The prevalence of FASP is currently estimated to be between 0.21% and 0.5%. Autosomal dominant mutations in circadian clock genes like PER2, CK1, PER3, CRY2, TIMELESS, and DEC2 have been linked to FASP, some with pleiotropic effects influencing other health aspects like migraine and depression. Early morning awakening is, instead, more common among older individuals, occurring in almost 4% of cases, without considering associated comorbidities. Advanced sleep-wake phase disorder (ASWPD) is characterized by a consistent and distressing anticipation of sleep-wake timing, affecting almost 1% of middle-aged individuals. On average, women have a shorter circadian period than men, making them more susceptible to ASWPD, albeit no significant gender discrepancies have been observed. Age-related alterations in circadian rhythms are exacerbated and compounded by neurodegenerative disorders, impacting the suprachiasmatic nucleus (SCN), sensitivity to light, and light responsiveness in those affected. Conflicting data has surfaced regarding the protective or detrimental effects of ASWPD in studies on aging, mild cognitive impairment (MCI), and diverse dementia conditions.