Mediterranean diet appears to weaken the depression–Alzheimer’s connection

A study of older individuals in Australia found that diet influences the relationship between depressive symptoms and Alzheimer’s disease biomarkers. In men with low adherence to the Mediterranean diet, higher levels of depressive symptoms were associated with elevated neurofilament light levels. This was not observed in men who closely followed the Mediterranean diet. The research was published in Neurobiology of Aging.

Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects memory, thinking, and behavior. It is the most common cause of dementia, usually beginning with subtle memory loss and advancing to severe cognitive and functional decline. The disease is associated with the accumulation of amyloid plaques and tau tangles in the brain (lumps of amyloid and tau proteins), leading to neuron damage and brain shrinkage.

Medical professionals use specific blood biomarkers of Alzheimer’s disease to detect early development of the disease and assist with diagnosis. The main blood biomarkers include the amyloid-beta 42/40 ratio, phosphorylated tau (p-tau181, p-tau217), and neurofilament light chain (NfL).

The amyloid-beta 42/40 ratio shows the balance between two types of amyloid proteins in the blood; a lower ratio usually indicates that more harmful amyloid has built up in the brain. Phosphorylated tau (p-tau181 or p-tau217) is a protein that increases when there are harmful changes in tau proteins in the brain; higher levels are strongly linked to Alzheimer’s progression. Neurofilament light chain (NfL) is a protein that rises when brain cells are damaged; elevated levels indicate neuronal injury from Alzheimer’s or other brain diseases.

Study author Hilal Salim Said Al Shamsi and colleagues examined whether dietary patterns influence the relationship between Alzheimer’s disease blood-based biomarkers and symptoms of anxiety and depression. They focused on three dietary patterns: the Mediterranean diet, the Western diet, and the Dietary Approaches to Stop Hypertension (DASH) diet.

The Mediterranean diet emphasizes fruits, vegetables, whole grains, legumes, fish, and olive oil, and is associated with better heart and brain health. The Western diet, high in red meat, processed foods, sugar, and saturated fat, has been linked to a greater risk of obesity, cardiovascular disease, and cognitive decline. The DASH diet focuses on reducing sodium and increasing intake of nutrient-rich foods like fruits, vegetables, and low-fat dairy to help lower blood pressure and promote overall health.

The researchers analyzed data from 89 cognitively unimpaired participants from the Australian Imaging, Biomarker and Lifestyle (AIBL) study of ageing. The AIBL study is a longitudinal project with participants re-assessed at 18-month intervals. All participants were aged 60 or older at baseline. The average age was 75, and 44% were male.

To be included, participants had to complete the Cancer Council of Victoria Food Frequency Questionnaire and undergo blood analysis for Alzheimer’s-related biomarkers (p-tau181, Aβ40, Aβ42, NfL, and GFAP) at their 72-month follow-up. Researchers used the food frequency data to calculate how closely each participant’s diet resembled the three targeted patterns. Participants also completed assessments of anxiety and depression using the Hospital Anxiety and Depression Scale and the 15-item Geriatric Depression Scale.

Results showed that Mediterranean and DASH diet scores were moderately correlated, indicating that individuals who adhered to one diet often adhered to the other. This reflects the shared emphasis on plant-based and minimally processed foods. By contrast, adherence to these two diets was only weakly correlated with adherence to the Western diet.

The researchers also found that individuals carrying the ε4 variant of the APOE gene—a genetic risk factor for Alzheimer’s disease—had higher levels of p-tau181 and NfL biomarkers.

Among men with low or medium adherence to the Mediterranean diet, greater depressive symptoms were associated with higher NfL levels. This association disappeared in men with high adherence to the diet. A similar pattern was found among individuals without the APOE ε4 allele: those with low or medium Mediterranean diet adherence showed a positive association between depressive symptoms and NfL levels, but this link was absent in high adherents. No significant relationships were found between depressive symptoms and Alzheimer’s biomarkers for the DASH or Western diet.

“Our study presents evidence of the moderating effect of the MeDi [Mediterranean diet] on the relationship between depressive symptoms and specific Alzheimer’s disease-related blood-based biomarkers, particularly highlighting the influence of genetic predispositions and sex differences. Overall, a higher MeDi score potentially mitigates some of the negative impact depressive symptoms have on Alzheimer’s disease-related blood-based biomarker alterations,” the authors concluded.

The study sheds light on the complex links between diet, mood, and Alzheimer’s disease biomarkers. However, the authors caution that the cross-sectional design does not allow causal conclusions. It remains unclear whether the differences in associations between depressive symptoms and NfL levels were caused by dietary patterns or by other unmeasured factors.

The paper, “The moderating effect of diet on the relationship between depressive symptoms and Alzheimer’s disease-related blood-based biomarkers,” was authored by Hilal Salim Said Al Shamsi, Samantha L. Gardener, Stephanie R. Rainey-Smith, Steve Pedrini, Hamid R. Sohrabi, Kevin Taddei, Colin L. Masters, Ralph N. Martins, and W.M.A.D. Binosha Fernando, for the AIBL research group.