Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease

Anna-Lena Richter; Marlies Diepeveen-de Bruin; Michiel G J Balvers; Lisette C P G M De Groot; Peter Paul  De Deyn; Sebastiaan Engelborghs; Renger F Witkamp; Yannick Vermeiren

doi:10.1159/000534492

Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease

Anna-Lena Richter, Marlies Diepeveen-de Bruin, Michiel G J Balvers, Lisette C P G M De Groot, Peter Paul De Deyn, Sebastiaan Engelborghs, Renger F Witkamp, Yannick Vermeiren

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Abstract

INTRODUCTION: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients on the potential association with cognition and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with serum serotonin (5-hydroxytryptamine, 5-HT) levels, cognitive/BPSD scorings, and cerebrospinal fluid (CSF) biomarker levels.

METHODS: Frozen serum samples of 25 well-characterized AD subjects as part of a previous BPSD cohort were analyzed, of which 15 had a neuropathologically confirmed diagnosis. Serum 25(OH)D3 levels were analyzed by means of LC-MS/MS, whereas 5-HT concentrations were quantified by competitive ELISA.

RESULTS: Among AD patients, vitamin D deficiency was highly prevalent, defined as levels below 50 nmol/L. Regression analyses, adjusted for age, gender, and psychotropic medications, revealed that serum 25(OH)D3 and 5-HT levels were positively associated (p = 0.012). Furthermore, serum 25(OH)D3 concentrations correlated inversely with CSF amyloid-beta (Aβ1-42) levels (p = 0.006), and serum 5-HT levels correlated positively with aggressiveness (p = 0.001), frontal behavior (p = 0.001), depression (p = 0.004), and partly with cognitive performance (p < 0.005). Lastly, AD patients on cholinesterase inhibitors had higher serum 25(OH)D3 (p = 0.030) and lower serum 5-HT (p = 0.012) levels.

CONCLUSIONS: The molecular associations between low vitamin D status, serum 5-HT, and CSF Aβ1-42 levels are highly remarkable, warranting further mechanistic and intervention studies to disclose potential involvement in the clinico-biobehavioral pathophysiology of AD.

Original language	English
Pages (from-to)	318-326
Number of pages	9
Journal	Dementia and Geriatric Cognitive Disorders
Volume	52
Issue number	5-6
Early online date	6 Oct 2023
DOIs	https://doi.org/10.1159/000534492
Publication status	Published - Mar 2024

Bibliographical note

Keywords

Humans
Serotonin
Alzheimer Disease/diagnosis
Chromatography, Liquid
Cross-Sectional Studies
Retrospective Studies
Tandem Mass Spectrometry
Vitamin D
Calcifediol
Vitamin D Deficiency

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Richter, Anna-Lena ; Diepeveen-de Bruin, Marlies ; Balvers, Michiel G J ; De Groot, Lisette C P G M ; De Deyn, Peter Paul ; Engelborghs, Sebastiaan ; Witkamp, Renger F ; Vermeiren, Yannick. / Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease. In: Dementia and Geriatric Cognitive Disorders. 2024 ; Vol. 52, No. 5-6. pp. 318-326.

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title = "Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease",

abstract = "INTRODUCTION: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients on the potential association with cognition and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with serum serotonin (5-hydroxytryptamine, 5-HT) levels, cognitive/BPSD scorings, and cerebrospinal fluid (CSF) biomarker levels.METHODS: Frozen serum samples of 25 well-characterized AD subjects as part of a previous BPSD cohort were analyzed, of which 15 had a neuropathologically confirmed diagnosis. Serum 25(OH)D3 levels were analyzed by means of LC-MS/MS, whereas 5-HT concentrations were quantified by competitive ELISA.RESULTS: Among AD patients, vitamin D deficiency was highly prevalent, defined as levels below 50 nmol/L. Regression analyses, adjusted for age, gender, and psychotropic medications, revealed that serum 25(OH)D3 and 5-HT levels were positively associated (p = 0.012). Furthermore, serum 25(OH)D3 concentrations correlated inversely with CSF amyloid-beta (Aβ1-42) levels (p = 0.006), and serum 5-HT levels correlated positively with aggressiveness (p = 0.001), frontal behavior (p = 0.001), depression (p = 0.004), and partly with cognitive performance (p < 0.005). Lastly, AD patients on cholinesterase inhibitors had higher serum 25(OH)D3 (p = 0.030) and lower serum 5-HT (p = 0.012) levels.CONCLUSIONS: The molecular associations between low vitamin D status, serum 5-HT, and CSF Aβ1-42 levels are highly remarkable, warranting further mechanistic and intervention studies to disclose potential involvement in the clinico-biobehavioral pathophysiology of AD.",

keywords = "Humans, Serotonin, Alzheimer Disease/diagnosis, Chromatography, Liquid, Cross-Sectional Studies, Retrospective Studies, Tandem Mass Spectrometry, Vitamin D, Calcifediol, Vitamin D Deficiency",

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doi = "10.1159/000534492",

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Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease. / Richter, Anna-Lena; Diepeveen-de Bruin, Marlies; Balvers, Michiel G J; De Groot, Lisette C P G M; De Deyn, Peter Paul ; Engelborghs, Sebastiaan; Witkamp, Renger F; Vermeiren, Yannick.

In: Dementia and Geriatric Cognitive Disorders, Vol. 52, No. 5-6, 03.2024, p. 318-326.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease

AU - Richter, Anna-Lena

AU - Diepeveen-de Bruin, Marlies

AU - Balvers, Michiel G J

AU - De Groot, Lisette C P G M

AU - De Deyn, Peter Paul

AU - Engelborghs, Sebastiaan

AU - Witkamp, Renger F

AU - Vermeiren, Yannick

PY - 2024/3

Y1 - 2024/3

N2 - INTRODUCTION: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients on the potential association with cognition and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with serum serotonin (5-hydroxytryptamine, 5-HT) levels, cognitive/BPSD scorings, and cerebrospinal fluid (CSF) biomarker levels.METHODS: Frozen serum samples of 25 well-characterized AD subjects as part of a previous BPSD cohort were analyzed, of which 15 had a neuropathologically confirmed diagnosis. Serum 25(OH)D3 levels were analyzed by means of LC-MS/MS, whereas 5-HT concentrations were quantified by competitive ELISA.RESULTS: Among AD patients, vitamin D deficiency was highly prevalent, defined as levels below 50 nmol/L. Regression analyses, adjusted for age, gender, and psychotropic medications, revealed that serum 25(OH)D3 and 5-HT levels were positively associated (p = 0.012). Furthermore, serum 25(OH)D3 concentrations correlated inversely with CSF amyloid-beta (Aβ1-42) levels (p = 0.006), and serum 5-HT levels correlated positively with aggressiveness (p = 0.001), frontal behavior (p = 0.001), depression (p = 0.004), and partly with cognitive performance (p < 0.005). Lastly, AD patients on cholinesterase inhibitors had higher serum 25(OH)D3 (p = 0.030) and lower serum 5-HT (p = 0.012) levels.CONCLUSIONS: The molecular associations between low vitamin D status, serum 5-HT, and CSF Aβ1-42 levels are highly remarkable, warranting further mechanistic and intervention studies to disclose potential involvement in the clinico-biobehavioral pathophysiology of AD.

AB - INTRODUCTION: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients on the potential association with cognition and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with serum serotonin (5-hydroxytryptamine, 5-HT) levels, cognitive/BPSD scorings, and cerebrospinal fluid (CSF) biomarker levels.METHODS: Frozen serum samples of 25 well-characterized AD subjects as part of a previous BPSD cohort were analyzed, of which 15 had a neuropathologically confirmed diagnosis. Serum 25(OH)D3 levels were analyzed by means of LC-MS/MS, whereas 5-HT concentrations were quantified by competitive ELISA.RESULTS: Among AD patients, vitamin D deficiency was highly prevalent, defined as levels below 50 nmol/L. Regression analyses, adjusted for age, gender, and psychotropic medications, revealed that serum 25(OH)D3 and 5-HT levels were positively associated (p = 0.012). Furthermore, serum 25(OH)D3 concentrations correlated inversely with CSF amyloid-beta (Aβ1-42) levels (p = 0.006), and serum 5-HT levels correlated positively with aggressiveness (p = 0.001), frontal behavior (p = 0.001), depression (p = 0.004), and partly with cognitive performance (p < 0.005). Lastly, AD patients on cholinesterase inhibitors had higher serum 25(OH)D3 (p = 0.030) and lower serum 5-HT (p = 0.012) levels.CONCLUSIONS: The molecular associations between low vitamin D status, serum 5-HT, and CSF Aβ1-42 levels are highly remarkable, warranting further mechanistic and intervention studies to disclose potential involvement in the clinico-biobehavioral pathophysiology of AD.

KW - Humans

KW - Serotonin

KW - Alzheimer Disease/diagnosis

KW - Chromatography, Liquid

KW - Cross-Sectional Studies

KW - Retrospective Studies

KW - Tandem Mass Spectrometry

KW - Vitamin D

KW - Calcifediol

KW - Vitamin D Deficiency

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U2 - 10.1159/000534492

DO - 10.1159/000534492

M3 - Article

C2 - 37806302

VL - 52

SP - 318

EP - 326

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

SN - 1420-8008

IS - 5-6

ER -

Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease

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