Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer’s disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 ± 1.1 yr) and in 82 age-matched controls (mean age, 76 ± 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41–80 yr of age [176± 58 (n = 29) and 330 ± 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin level...

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Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype.

Melatonin rhythmicity: effect of age and Alzheimer's disease.

Women's sleep in health and disease

https://www.amjmed.com/article/S0002-9343(99)00266-1/pdf

Do plasma melatonin concentrations decline with age

https://pure.knaw.nl/ws/files/487700/14926_285_swaab.pdf

Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer's disease.

Twenty-four-h urine samples, divided into two fractions representing night- and daytime melatonin production, were collected from 115 healthy individuals between the ages of 3 and 80, of known height and weight, and assayed for 6-hydroxy melatonin sulphate (SaMT), a major urinary metabolite of melatonin, by gas chromatography mass spectrometry. The population was divided for analytical purposes into children (boys aged 3-10.99, girls aged 3-9.59), adolescents (males aged 11-17.99, females aged 9.60-17.99), and adults (men and women over 18). The results showed approximately the same excretion over 24 h in all 3 groups but that the night/day ratio was considerably greater in children and adolescents compared to adults (P less than 0.001). However, when the results were expressed as a function of body weight (BW), body surface area (BSA), or creatinine excretion (CE), nocturnal SaMT was higher in children than in adults (P less than 0.001 for all 3 parameters) or adolescents (BW, P less than 0.001; BSA, P less than 0.002; CE, P less than 0.001) and was higher in adolescents than in adults (BW and BSA, P less than 0.001). Children also excreted more during the day than adults (BW, P less than 0.01; CE, P less than 0.001) or adolescents (BW alpha CE, P less than 0.02). Our results show that pineal output barely changes during childhood and adolescence. However, there is an age related decrease in SaMT excretion/unit body mass which correlates with an age-related increase in body mass. We therefore conclude that the decrease in circulating levels of melatonin during growth and sexual maturation is brought about by an increase in body mass.

Ian M. Young

Papers

Constant pineal output and increasing body mass account for declining melatonin levels during human growth and sexual maturation