Vitamin D in the development and progression of alzheimer’s disease: implications for clinical management

ABSTRACT

Introduction

Although the pathophysiological bases of Alzheimer’s disease (AD) remain incompletely understood and disease-modifying therapies are not available, intervention on modifiable risk factors is warranted. Research on nutrition and dietary components is challenging and controversies still persist about the role of micro- and macronutrients and health outcomes in dementia. Importantly, results of preclinical investigations have shown that vitamin D triggers different neural pathways that may be protective against these neurodegenerative mechanisms, including the deposition of amyloid plaques, inflammatory processes, neurofibrillary degeneration, glutamatergic excitotoxicity, excessive intraneuronal calcium influx, and oxidative stress, although its relationship with AD still needs to be fully understood.

Areas covered

The authors analyzed the recent evidence about the effects of vitamin D insufficiency on AD and the role of supplementation.

Expert opinion

Both insufficient (25–49.9 ng/ml) and deficient levels (<25 ng/ml) of vitamin D may contribute to an increased susceptibility to AD. However, further well-designed prospective studies are needed for a better understanding of the involvement of low vitamin D concentrations in the AD natural history. Randomized clinical trials will also be necessary to address the issue of causality and determine whether vitamin D supplementation may be effective for the prevention or treatment of AD.

KEYWORDS:

• Calcitriol
• alzheimer’s disease
• mild cognitive impairment
• amyloid-β clearance
• neurosteroid
• supplementation
• neurotrophic factor
• nutritional frailty

Article highlights

• During the last 15 years, several drugs antagonizing amyloid-β (Aβ) aggregation or increasing Aβ brain clearance have been tested in mild-to-moderate Alzheimer’s disease (AD) patients without success.

• Given the absence of preventive or curative interventions for AD and other neurodegenerative dementias, the search for potentially modifiable risk factors for these conditions, such as diet, is of paramount importance.

• Vitamin D is often referred to as a neurosteroid, because a growing body of evidence has suggested that its deficiency is involved in the pathogenesis of chronic brain conditions, including the development of AD and other dementias in older age.

• Low vitamin D status was associated with an accelerated decline of cognitive function domains in ethnically diverse older adults, who exhibited a high prevalence of vitamin D insufficiency or deficiency.

• The link between vitamin D dosage and cognitive decline does not appear to be dose-response: the neuroprotective effects of vitamin D may be attained only at moderate rather than at low or high concentrations.

• It may be justified to supplement vitamin D (probably in association to curcumin) only if deficient in a patient, to improve cognitive performance, although future research should focus on larger, controlled randomized trials in different populations.

• Delaying AD onset is possible thanks to the Mediterranean diet (MeDi) pattern, but current evidence supporting vitamin D supplementation for preventing AD is scarce.

Acknowledgments

The authors thank the MICOL Study group and the “Salus in Apulia” Research Team. This manuscript is the result of the research work undertaken by the “Research Network on Aging” team, supported by the resources of the Italian Ministry of Health – Research Networks of National Health Institutes. The authors thank MV. Pragnell for her precious help as a native English supervisor.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.