Does dietary intake of caffeine have an effect on transient global amnesia?

Abstract

Aim

Amnesia is a cognitive disorder that may lead to memory loss. Caffeine is a psychoactive substance which have an effect on memory and cognitive functions. This study aimed to assess the association of transient global amnesia (TGA) with dietary intake of caffeine.

Methods

This cross‐sectional study was conducted on the Sabzevar Persian cohort data of 258 patients with TGA and 520 healthy individuals in Sabzevar, Iran. The Nutritional data were gathered in face‐to‐face interviews using a valid Food Frequency Questionnaire. Different models of logistic regression were used to determine the association between TGA and dietary caffeine intake after adjusting the confounders including age, sex, education, job, marital status, physical activity, BMI, and calorie intake.

Results

There was no significant difference in terms of dietary calorie intake of (2279.5 ± 757.9 vs. 2365.5 ± 799.5, p = 0.19), protein (70.79 ± 25.27 vs. 72.94 ± 24.83, p = 0.31), fat (59.97 ± 23.79 vs. 60.13 ± 26.38, p = 0.93), carbohydrate (376 ± 134 vs. 393.1 ± 137.8, p = 0.14), and caffeine (196.4 ± 127.9 vs. 186.3 ± 128.5, p = 0.36) between the groups. No significant association was found between TGA and dietary intake of caffeine (OR: 0.99, 95% CI: 0.99–1.01, p = 0.36). The results did not change after adjusting the confounders.

Conclusions

No significant association was found between TGA and dietary intake of caffeine. Further prospective studies are required to confirm this finding.

INTRODUCTION

Amnesia is a cognitive disorder distinguished by the complete or partial loss of short-term and/or long-term memory and may manifest as an inability to recall past events, experiences, or information.¹ Head traumas, neurological disorders, psychological stress, and some substances or medications can cause amnesia.² There are different types of amnesia, including retrograde amnesia (loss of memories that occurred before the amnesia-inducing event) and anterograde amnesia (difficulty forming new memories after the event).³ The global prevalence of cognitive impairment is about 19.0%.⁴ Transient global amnesia (TGA) is characterized by the sudden onset of anterograde amnesia, generally lasting up to 24 h.⁵ The annual incidence of TGA was reported to be 14.3 per 100 000 people.⁶

Cognitive deficits are caused by a reduction in cholinergic activity in the brain,⁷ an elevation in oxidative stress,⁸ neuroinflammatory reactions,⁹ and hypercholesterolemia.¹⁰ In recent years, considerable effort has been invested in developing cognition-enhancing medicines and dietary supplements to combat age-related cognitive decline and dementia-related syndromes.¹¹

Recently, there has been an increased interest in cognitive effects of caffeine as a psychotropic compound included in a variety of drinks and foods.¹² Coffee is commonly acknowledged as a prominent dietary source of caffeine; however, it is also present in other beverages such as tea, energy drinks, carbonated soft drinks and in certain fruits and foods that contain cocoa.^13,14 Caffeine is incorporated into the circulation throughout the body following caffeine ingestion¹⁵ and acts as an antagonist for adenosine A1 and A2A receptors.¹⁵ Caffeine can affect metabolism, the cardiovascular and respiratory systems, and neuroinflammatory, neuromodulator, and neuroprotective processes by inhibiting adenosine receptors.^16,17 Caffeine has the potential to impede neurodegeneration, increase anxiety, psychomotor acuity by inhibiting NMDA receptors.^18–20 Due to the literature review, there is no study to evaluate the association between TGA and dietary caffeine, but previous studies evaluated the relationship between caffeine and cognitive disorders in humans. According to animal model research, caffeine can mitigate cognitive decline.²¹ Based on the findings of other research, consuming caffeine may either delay the onset or reduce the risk of developing of Alzheimer's disease (AD).^22,23

Epidemiological human studies on the protective effects of caffeine against cognitive impairment and dementia have yielded inconsistent results. Several studies indicated that caffeine intake may have a beneficial impact on neurological disorders and dementia,^24,25 whereas others have found no association between caffeine and dementia.^26,27 Therefore, the association between caffeine consumption with cognitive decline and dementia remains inconclusive. So, we designed this study to evaluate the association between caffeine consumption and TGA in the Iranian adult population.

METHODS

This cross-sectional research is based on the Sabzevar Persian cohort of 258 patients with TGA and 520 healthy individuals from Sabzevar, Iran. As inclusion criteria, participants were required to fill out an informed consent form, have a confirmed diagnosis of TGA, not use caffeine supplements, and no dietary restrictions or intolerances. In addition, failure to gather necessary data or a participant's refusal to continue participating in the research was considered as exclusion criteria.

The information for socioeconomic status was obtained from the Persian cohort questionnaire. Patients were weighed barefoot and in light clothing on a mechanical scale (SECA 755) to the closest 0.1 kg. Standing height was measured with an accuracy of 0.5 cm using a stadiometer (SECA 204) mounted on the wall. The International Classification of Diseases code (ICD-10: code G45.4) was used to screen all research participants. A neurologist visited all patients and confirmed the TGA diagnosis.

Dietary intake

The valid Persian Food Frequency Cohort Questionnaire (FFQ) was utilized to evaluate the diet information²⁸ via face-to-face interviews. Portion sizes were determined using household measurements and then converted to grams. Energy and nutrient content were evaluated using the Food Composition Table (FCT) from the United States Department of Agriculture (USDA). The composition table of Iranian cuisines was utilized for Iranian meals that were not available in the FCT. The data collected from the FFQ were converted into grams of nutrients using a modified version of Nutritionist-IV software for Iranian cuisine in order to determine the quantity of caffeine intake from the diet.

Statistical analyses

Baseline quantitative and qualitative variables were analyzed by independent samples t-test and chi-square methods, respectively. We used logistic regression to determine the relationship between TGA and dietary caffeine intake in both the crude and adjusted models as follows: model 1: crude, model 2: adjusted for age and sex, model 3: further adjustment for education, job, marital status, model 4: further adjustment for physical activity and BMI, and model 5: additional adjustment for calorie intake. p < 0.05 was considered as significant, and all the analyses were done by SPSS version 22.

RESULTS

Characteristics of the participants are presented in Table 1. A total of 258 patients (mean age = 49.86 ± 8.82 years, females: 55.4%) and 520 controls (mean age = 49.66 ± 9.37 years, females: 72.5%) were included in the study. The cases had higher RBC (4.79 ± 0.55 vs. 4.56 ± 0.42, p < 0.01), BUN (13.63 ± 3.44 vs. 13.02 ± 3.64, p < 0.01), LDL-C (111.71 ± 30.76 vs. 103.07 ± 30.95, p < 0.01), and ALP (222.80 ± 66.2 vs. 210.76 ± 57.2, p < 0.01) and lower WBC (6.32 ± 1.68 vs. 6.61 ± 1.51, p < 0.01) than the controls. In addition, the cases had higher alcohol consumption than the controls (10% vs. 5%, p = 0.03).

TABLE 1 Characteristics of participants.

	Controls	Cases	p
Age (years)	49.66 ± 9.37	49.86 ± 8.82	0.79
Gender (females, n (%))	187 (72.5)	168 (55.4)	0.001
Has job, n (%)	72 (27.9)	151 (49.8)	0.001
Use alcohol, n (%)	13 (5.0)	30 (10.1)	0.03
Smoking, n (%)	11 (29.7)	21 (42.0)	0.45
MET (kcal/kg*h)	39.18 ± 9.8	38.04 ± 8.00	0.13
Height (cm)	161.91 ± 9.7	159.28 ± 9.07	0.001
Weight (kg)	74.53 ± 14.6	72.21 ± 12.3	0.04
BMI (kg/m2)	28.44 ± 5.01	28.49 ± 4.64	0.90
Right SBP (mmHg)	113.46 ± 14.42	112.04 ± 16.01	0.27
Right DBP (mmHg)	72.18 ± 9.8	70.57 ± 10.6	0.06
WBC (K/μL)	6.61 ± 1.51	6.32 ± 1.68	0.03
RBC (M/μL)	4.56 ± 0.42	4.79 ± 0.55	0.001
Hb (g/dL)	14.07 ± 1.59	13.81 ± 1.50	0.06
HCT (%)	40.31 ± 3.85	40.64 ± 4.06	0.33
MCV (fL)	88.48 ± 5.3	85.11 ± 5.73	0.001
MCH (pg)	30.89 ± 2.4	28.95 ± 2.52	0.001
MCHC (g)	34.87 ± 1.12	33.99 ± 1.42	0.001
Platelets (K/μL)	250.96 ± 58.5	284.01 ± 71.77	0.001
Lymphocytes (106/L)	38.46 ± 9.01	40.49 ± 9.21	0.009
Monocytes (106/L)	4.48 ± 0.08	4.03 ± 0.10	0.001
Granulocytes (106/L)	57.04 ± 9.51	55.44 ± 9.86	0.05
RDW (%)	12.44 ± 1.18	11.78 ± 1.19	0.001
PCT (ng/mL)	0.23 ± 0.05	0.25 ± 0.06	0.001
MPV (fL)	9.53 ± 0.70	9.16 ± 0.77	0.001
PDW (%)	16.38 ± 0.59	16.53 ± 0.96	0.03
FBS (mg/dL)	108.74 ± 44.10	109.15 ± 46.20	0.91
BUN (mg/dL)	13.02 ± 3.64	13.63 ± 3.44	0.04
Creatinine (mg/mL)	1.07 ± 0.18	1.06 ± 0.18	0.67
TG (mg/dL)	162.65 ± 151.64	144.15 ± 82.13	0.06
Cholesterol (mg/dL)	187.53 ± 40.78	193.39 ± 38.09	0.08
SGOT (IU/L)	20.84 ± 7.46	20.50 ± 15.99	0.75
SGPT (IU/L)	21.40 ± 12.28	21.15 ± 17.72	0.84
ALP (IU/L)	210.76 ± 57.2	222.80 ± 66.2	0.02
HDLC (mg/dL)	52.77 ± 11.47	52.99 ± 10.36	0.82
LDLC (mg/dL)	103.07 ± 30.95	111.71 ± 30.76	0.001
GGT (IU/L)	27.20 ± 18.88	24.52 ± 19.26	0.10

Table 2 presents a comparison of dietary intake between the case and control groups. There was no significant difference observed in terms of energy (2279.5 ± 757.9 vs. 2365.5 ± 799.5, p = 0.19), protein (70.79 ± 25.27 vs. 72.94 ± 24.83, p = 0.31), total fat (59.97 ± 23.79 vs. 60.13 ± 26.38, p = 0.93), carbohydrate (376 ± 134 vs. 393.1 ± 137.8, p = 0.14), and caffeine (196.4 ± 127.9vs.186.3 ± 128.5, p = 0.36).

TABLE 2 Dietary intake of nutrients in the cases and controls.

	Controls	Cases	p
Protein (g/day)	72.94 ± 24.83	70.79 ± 25.27	0.31
Total fat (g/day)	60.13 ± 26.38	59.97 ± 23.79	0.93
Carbohydrate (g/day)	393.1 ± 137.8	376.0 ± 134.0	0.14
Energy (kcal/day)	2365.5 ± 799.5	2279.5 ± 757.9	0.19
Caffeine (mg/day)	186.3 ± 128.5	196.4 ± 127.9	0.36

The association of amnesia with caffeine is shown in Table 3. No significant association was found between TGA and caffeine (OR: 0.99, 95% CI: 0.99–1.01, p = 0.36). The results did not change after adjustment for age and sex (OR: 0.99, 95% CI: 0.99–1.0, p = 0.11) (Model 2), further adjustment for education, job, and marital status (OR: 0.99, 95% CI: 0.99–1.0, p = 0.12) (Model 3), further adjustment for physical activity and BMI (OR: 0.99, 95% CI: 0.99–1.0, p = 0.23) (Model 4), and additional adjustment for calorie intake (OR: 0.99, 95% CI: 0.99–1.0, p = 0.41) (Model 5) (Figure 1).

TABLE 3 The association of transient global amnesia with caffeine.

	Model 1	Model 2	Model 3	Model 4	Model 5
OR	95% CI	p	OR	95% CI	p	OR	95% CI	p	OR	95% CI	p	OR	95% CI	p
Caffeine	0.99	0.99–1.01	0.36	0.99	0.99–1.0	0.11	0.99	0.99–1.0	0.21	0.99	0.99–1.0	0.23	0.99	0.99–1.0	0.41

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DISCUSSION

Our study examined the link between TGA and dietary caffeine intake in a large group of participants and found no significant association between TGA and caffeine. The findings of prior epidemiologic investigations on the relationship between caffeine use and cognitive function in humans have been inconsistent.²⁹ The findings of a prospective cohort study conducted in Portugal,³⁰ including both male and female participants, demonstrated an association between caffeine intake and a reduced risk of cognitive decline in women. However, it is essential to mention that the association was not statistically significant among males. On the contrary, a cross-sectional study conducted in Iran utilized data from the 2013 to 2014 National Health and Nutritional Examination Surveys to examine the relationship between caffeine intake and cognitive function and found a modest positive association between caffeine consumption and cognitive function, with a greater association observed among males.³¹ Furthermore, previous investigations have demonstrated that the consumption of caffeine is related to a reduced risk of developing some neurological disorders, such as Parkinson's disease, in healthy individuals. Furthermore, individuals with Parkinson's disease experienced a slower rate of disease progression, suggesting potential advantages of caffeine associated with the inhibition of adenosine 2A receptors.³²

Several factors such as type of caffeine may influence the effect of caffeine on memory function. For example, Yuan Zhang et al. showed heavy instant coffee and moderate decaffeinated coffee consumption were associated with a higher risk of dementia. In comparison, moderate ground coffee consumption was associated with a lower risk, particularly in individuals at high genetic risk for dementia.³³ In other studies, daily coffee intake was inversely associated with brain size but non-linearly connected with dementia risk, with a higher risk of dementia in those consuming more than six cups but less so with stroke.³⁴ Although Caffeine can provide potential benefits through multiple pathways, such as reducing Aβ production, preventing tau hyperphosphorylation, mitigating oxidative stress, and influencing adenosine-related neurotransmission,³⁵ it can be variable based on the type of caffeine beverages, dosage, frequency, and age of consumption of caffeine.³⁶

However, this study had some limitations. The estimation of caffeine consumption may have been inaccurate due to the reliance on a FFQ to assess daily intake of caffeine. However, we expect that any misclassification of caffeine intake would have been random concerning outcome assessment. For better results, future studies should use a more accurate method to quantify caffeine intake, such as measuring caffeine levels in blood or urine samples. Also, interventional studies using caffeine supplements in people with TGA may help to draw definitive conclusions in this field.

CONCLUSION

We investigated the association between TGA and caffeine and no significant difference was found between TGA and dietary intake of caffeine. Further prospective studies are required to provide more clarity on the effect of different types and doses of caffeine on different types of amnesia.

AUTHOR CONTRIBUTIONS

SD, MZ, ZM, AA, MS, BAK, MM, KAM, and MG designed the study and were involved in the data collection, analysis, and drafting of the manuscript. MG, NV, SM, SK, AK, and SD were involved in the design of the study, analysis of the data, and critical review the manuscript. All authors read and approved the final manuscript.

FUNDING INFORMATION

This study is financially supported by the Student Research Committee of Sabzevar University of Medical Sciences, Sabzevar, Iran (Code 402192). Thanks to all the colleagues in the research committee for their nice cooperation.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT

Not all data are freely accessible because no informed consent was given by the participating agencies for open data sharing. However, the data are available from the corresponding author upon reasonable request.

ETHICS STATEMENT

Approval of the Research Protocol by an Institutional Reviewer Board: This study was approved by the Ethical Committee of the Research Ethics Committee of the Sabzevar University of Medical Sciences, Sabzevar, Iran (code: IR.MEDSAB.REC.1400.049). All procedures of the studies involving human participants were by the ethical standards of the institutional and/or national research committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent: All participants signed informed consent forms. Informed consent was obtained from the adolescents and their parents to participate in the study.

Registry and the Registration No. of the Study/Trial: N/A.

Animal Studies: N/A.

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