Effects of Alpha-lactalbumin Intake on Metabolic and Cognitive Functions in Elderly

Aging modifies the metabolic pathway of the neurotransmitter serotonin by reducing the synthesis rate and increasing the breakdown rate of serotonin, possibly related to the observed enhanced sensitivity of the serotonergic pathway. Since serotonin plays a prominent role in neuropsychological functions such as anxiety, mood and memory, the enhanced sensitivity of the serotonergic pathway in aging can probably explain the fact that elderly are more vulnerable to develop cognitive deficits and depressive symptoms.

Serotonin synthesis in brain is regulated by its precursor tryptophan (TRP). Because tryptophan is an essential amino acid, modifying the availability of tryptophan through dietary intake, can directly influence central serotonin metabolism and consequently affective and cognitive processes.

The aim of this study is to test the hypothesis that an acute intake of whey protein with high levels of TRP such as alpha-lactalbumin can stabilize the metabolism of serotonin and subsequently enhance metabolic and cognitive functions in healthy older adults. The acute effects of this dietary protein will be investigated in subjects with mild cognitive impairment (MCI), or dementia, compared to control subjects in order to examine whether healthy older subject with MCI benefit more from the intake of alpha-lactalbumin and/or whey. The investigators will investigate if this meal can optimize serotonin metabolism by elevating plasma TRP levels and plasma TRP appearance and enhance splanchnic TRP extraction. In addition, the effects on mood and cognitive functions will be examined.

The study involves for all subjects 3 test days (approximately 8 hours each). On this test day the investigators will examine the acute effects of a protein meal. Subjects will receive a mixture of alpha-lactalbumin and/or whey and/or casein, carbohydrates and amino acid stable isotopes to investigate protein and amino acid kinetics (assigned to alpha-lactalbumin or whey or casein group on test day 1, then switch on test day 2 and 3). The subjects will receive these stable isotopes by infusion in their blood and by oral intake (e.g. simultaneously with protein meal). For study purposes, blood will be drawn approx. 25 times during 8 hours on the test day, altogether about 100-120 ml of blood will be drawn on the test day.

Eligibility Criteria:
Inclusion criteria subjects with dementia:

* Dementia diagnosis
* Ability to walk, sit down and stand up independently
* Age 55 years or older
* Ability to lie in supine or elevated position for 8 hours
* Willingness and ability to comply with the protocol, including:

Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Inclusion criteria healthy subjects:

* Healthy male or female according to the investigator's or appointed staff's judgment
* Ability to walk, sit down and stand up independently
* Age 55 years or older
* Ability to lie in supine or elevated position for 8 hours
* Willingness and ability to comply with the protocol, including:

Adhering to fasting state from 10 pm ± 2h onwards the day prior to each study visit

Exclusion Criteria:

* Any condition that may interfere with the definition 'healthy subject' according to the investigator's judgment (for healthy control group only)
* Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
* Indication of severe cognitive impairment (MOCA score \< 17)
* Established diagnosis of Insulin Dependent Diabetes Mellitus
* History of untreated metabolic disease(s) including hepatic or renal disorder
* Presence of acute illness or metabolically unstable chronic illness
* Presence of fever within the last 3 days
* Preplanned surgery of procedures that would interfere with the conduct of the study
* Any other condition according to the PI or study physician that would interfere with proper conduct of the study / safety of the patient
* Current alcohol or drug abuse
* Known allergy to milk or milk products
* Use of long-term oral corticosteroids or short course of oral corticosteroids 4 weeks preceding first test day
* Use of protein or amino acid containing nutritional supplements within 5 days of test day
* (Possible) pregnancy
* BMI of \< 18.5 or ≥ 40 kg/m2
* Dietary or lifestyle characteristics: When during the period from enrollment to completion of the study (end of test day) any condition is developed, whether causing the subject to not meet inclusion criteria or to meet exclusion criteria, the subject will be excluded from the study