Vitamin D deficient seniors in acute care were more agitated and disinhibited – April 2024

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Vitamin D and behavioral disorders in older adults: results from the CLIP study

The Journal of nutrition, health and aging – Vol 28, Issue 4, April 2024, https://doi.org/10.1016/j.jnha.2024.100205
Lucie Gilbert a, Alexis Bourgeais b, Spyridon N Karras c, Duygu Gezen-Ak d, Erdinç Dursun d, Cédric Annweiler a b e f g

Objectives: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients.

Design: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement.

Setting: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring.

Participants: 272 patients ≥65 years consecutively hospitalized or seen in consultation.

Measurements
Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders.

Results
Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but

• higher (i.e., worse) subscore of agitation
  • and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and
• higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02)

than those without vitamin D deficiency (n = 194).
In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (β = 1.37, p = 0.005) and with the subscore of disinhibition (β = 0.96, p = 0.008).

Conclusion
Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.
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Clipped from discussion section of PDF

Vitamin D deficiency was not associated in geriatric patients with the NPI-score as a whole but was associated specifically with higher (i.e., worse) NPI-R subscores of agitation and aggressiveness and of disinhibi­tion. This provides a scientific basis for conducting clinical trials to test the efficacy of vitamin D supplementation to prevent or improve the prognosis of behavioral disorders in older patients with initial serum 25OHD < 25 nmol/L.
These findings are consistent with previous animal experimentation and neuropsychological literature in humans. Previous studies have reported that transgenic mice lacking functional vitamin D receptors (VDR) more often showed abnormal social behaviors compared to wild­type mice, in particular more often aggressiveness and a risk of cannibalism [15,16]. Interestingly, another animal model of Develop­mental vitamin D (DVD) deplete adult rats (i.e., rats subjected to transient low prenatal vitamin D) generated an animal model of schizophrenia [17]. In humans, the neuropsychoepidemiological literature found that individuals with hypovitaminosis D had increased risks of incidental depression [18], psychosis [18] and cognitive decline [7,8], notably an increased risk of Alzheimer disease [19]. Specifically, the cognitive risk appeared mainly as a decline of executive functions [20], in particular of cognitive inhibition [21]. Finally, in addition to chronic neurocognitive disorder, there is also a greater risk of acute decompensation in the form of delirium among those with hypovitaminosis D [10], which is usually expressed by disturbed behavior. Compared to previous literature, we provide here the first evidence that the cognitive risk is coupled with a risk of behavioral symptoms including agitation, aggressiveness and disinhi­bition in older adults with vitamin D deficiency. These novel findings suggest that the correction of vitamin D deficiency could represent an interesting therapeutic option to prevent and/or cure behavioral disorders in older adults. Consistently, an international expert consensus concluded that vitamin D supplementation should be administered to people with neurocognitive disorders [8], and previous randomized trials reported improved executive functioning in supplemented participants compared to those receiving a placebo [22]. Similarly, a pre-post study also found improved NPI score among older adults after 4 weeks of vitamin D2 supplementation [23].
Mechanisms linking vitamin D to behavior are not fully elucidated. VDRs were found in neurons and glial cells from brain areas that are essential to cognitive function (temporal cingular and orbital cortex, thalamus, nucleus accumbens, stria terminalis and amygdala) [24]. By modifying the gene expression of various proteins, vitamin D modulates neurophysiology and neuroprotection [4]. Specifically, vitamin D regulates neurotrophic agents and controls cell differentiation and maturation [25], as well as the gene expression of various neuro­transmitters including acetylcholine, dopamine and serotonin [6]. Vitamin D also limits inflammatory changes associated with aging in hippocampus [26], prevents the accumulation of Ab peptides by stimulating phagocytosis [27] and blood-brain barrier efflux transport [28]. As a consequence, hypovitaminosis D is associated with changes in brain volume, vascularization and metabolism [4,5]; all changes that may explain the greater risk of behavioral disorders in the case of vitamin D deficiency. Nevertheless, causality could not be deducted from our observational study, and behavioral disorders may actually be the expression of an altered cognitive status responsible for hypovitaminosis D because of disability and subsequent decreased food intakes and sun exposure. . . . . .

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VitaminDWiki – Seniors contains:

429 items in Seniors

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13 reasons why many seniors need more vitamin D (both dose and level) - July 2023 has:

1. Senior skin produces 4X less Vitamin D for the same sun intensity
2. Seniors have fewer vitamin D receptor genes as they age
   Receptors are needed to get Vitamin D in blood actually into the cells
3. Many other Vitamin D genes decrease with age
4. Since many gene activations are not detected by a blood test,
   more Vitamin D is often needed, especially by seniors
5. Seniors are indoors more than when they were younger
   not as agile, weaker muscles; frail, no longer enjoy hot temperatures
6. Seniors wear more clothing outdoors than when younger
   Seniors also are told to fear skin cancer & wrinkles
7. Seniors often take various drugs which end up reducing vitamin D
   Some reductions are not detected by a vitamin D test of the blood
   statins, chemotherapy, anti-depressants, blood pressure, beta-blockers, etc
8. Seniors often have one or more diseases that consume vitamin D
   osteoporosis, diabetes, Multiple Sclerosis, Cancer, ...
9. Seniors generally put on weight as they age - and a heavier body requires more vitamin D
10. Seniors often (40%) have fatty livers – which do not process vitamin D as well
11. Reduced stomach acid means less Magnesium is available to get vitamin D into the cells
12. Vitamin D is not as bioavailable in senior intestines
13. Seniors with poorly functioning kidneys do not process vitamin D as well
       Seniors category has 429 items

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VitaminDWiki – Higher conscientiousness, extraversion related to higher vitamin D in seniors – Feb 2023