Nutrition's crucial role in Alzheimer's progression revealed

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Mar 10 2024

In a recent cross-sectional study published in the journal Frontiers in Nutrition, researchers used data from 266 participants along the cognitive impairment spectrum to investigate the association between nutrition and cognitive decline. Their study reveals that nutrition-related variables such as body composition and dietary patterns are significantly associated with the onset and progression of Alzheimer's disease (AD), with malnutrition substantially increasing AD risk. Since malnutrition presents an easily adjustable, safe, and non-invasive health behavior, the early identification of at-risk populations and dietary interventions therein may substantially reduce the future global burden of AD and similar cognitive disabilities.

Study: An investigation into the potential association between nutrition and Alzheimer’s disease. Image Credit: Adisak Riwkratok / Shutterstock

Diet and cognitive health

One of humanity's crowning achievements is longevity – modern medicine's lengthening of natural human lifespans. An unfortunate side-effect of this achievement, however, is a slowly aging world, with more senior citizens alive today than ever before and a corresponding explosion in the incidence and prevalence of chronic, age-associated conditions such as cardiovascular diseases, cognitive declines, and some cancers. While initially presenting a 'safer' (lower mortality) pathology than cancers and cardiovascular diseases, cognitive declines are alarmingly debilitating conditions, resulting in substantial economic and mental trauma for patients and their families, even before accounting for their potentially lethal comorbidities.

Alzheimer's disease (AD) is the most common cognitive disorder associated with old age. It is a chronic, progressive disease characterized by initial mild memory loss, which eventually declines into severely debilitating dementia. It is caused by the deposition of specific proteins, which results in the loss of neural connections. Despite substantial research in the field, a cure for the condition remains elusive, with clinical interventions focused on symptom management and progression delay.

Recently, studies have suggested a link between malnutrition and dementia. The European Society for Clinical Nutrition and Metabolism (ESPEN) has further classified malnutrition as the most common AD-associated comorbidity. Unfortunately, research has failed to establish an association between specific nutritional components and their impacts on the different stages of AD progression. Understanding the holistic relationship between multiple nutritional indices and their implications on various stages of AD would allow clinicians and dieticians the information needed to curb the prevalence of these cognitive disorders.

About the study

The present study aimed to investigate the relationship between various commonly used nutritional indices and their respective contributions to AD risk and progression. The sample cohort was recruited from the Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University.

Between April 2019 and April 202, 946  participants with mild cognitive impairment (MCI due to AD – 'AD-MCI') or dementia due to AD ('AD-D') without other neurological conditions relating to cognition (e.g., Parkinson's disease) and non-diet-based malnutrition (prevalence of hematological tumors, liver cirrhosis) were enrolled. Of these, 266 participants presented completed demographic and medical information and were included in the final analyses. These comprised 73 controls (normal cognition – 'NC'), 72 AD-MCI, and 121 AD-D samples.

Subject body composition metrics were measured using the Global Leadership Initiative on Malnutrition (GLIM) criteria. These included 'reduced food intake,' 'non-volatile weight loss,' 'muscle mass,' and 'body mass index (BMI).' Additionally, subjects' dietary patterns (e.g., Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay [MIND]) were recorded, and the nutritional composition of these diets was separately investigated.

Venous blood samples were used for the estimations of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), hemoglobin, creatinine, total calcium, albumin, globulin, albumin/globulin (A/G), and other nutritional status determinants.

Study findings

The present study comprised 266 participants, 57.14% of whom were female, with a mean age of 64.89 years. Medical data revealed that 36.84% of participants carried the APOE ε4 allele, a common culprit in AD pathology. Body composition metrics showed that AD-D patients had, on average, substantially lower arm, waist, calf, and hip circumferences and lower BMIs compared to AD-MCI and NC cohorts. Surprisingly, all participants were found to follow some interpretation of either Mediterranean or MIND dietary patterns, which did not differ in their nutritional scores.

"…a smaller waist circumference was linked to lower level of β amyloid protein (Aβ) and higher levels of phosphorylated tau (P-tau) and total tau (T-tau) in the cerebrospinal fluid of AD patients. This phenomenon may be attributed to the utilization of skeletal muscle mass as a nutritional reservoir in response to a prolonged state of negative energy balance during disease. Consequently, the muscle mass of AD patients gradually decreases as the disease progresses in AD."

Nutritional assessment scales present that the AD-D cohort fared worse than the NC and AD-MCI groups. Study data analyses show that BMI and AD occurrence are independently associated, validating previous research.

Investigations into specific nutritional variables revealed that body composition, nutritional assessment scales, and blood-based nutritional laboratory variables were significantly associated with the occurrence and progression of AD. Malnutrition was found to be most prevalent in the AD-D cohort, but prevalence in even the AD-MCI was shown to be substantially higher than in the NC group.

"Since malnutrition is a risk factor that can be intervened, early identification and intervention of individuals with nutritional risk or malnutrition are significantly beneficial for reducing the risk, development, and progression of AD."