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Review

A Life Course Approach to Understanding Cognitive Impairment in Adults with Type 2 Diabetes: A Narrative Literature Review

by
Bohyun Kim
1,
Jimmy T. Efird
2,3 and
Jie Hu
1,*
1
College of Nursing, The Ohio State University, 1585 Neil Ave, Columbus, OH 43210, USA
2
VA Cooperative Studies Program Coordinating Center, Boston, MA 02111, USA
3
School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
*
Author to whom correspondence should be addressed.
Diabetology 2023, 4(3), 323-338; https://doi.org/10.3390/diabetology4030028
Submission received: 1 July 2023 / Revised: 4 August 2023 / Accepted: 10 August 2023 / Published: 14 August 2023
(This article belongs to the Special Issue Exclusive Papers Collection of Editorial Board Members in Diabetology)
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Review Reports Versions Notes

Abstract

:
Diabetes is an independent risk factor for cognitive impairment, with the latter presenting challenges for diabetes self-management and glycemic control in individuals with type 2 diabetes. Predicated on the theory of unpleasant symptoms, the purpose of the current narrative review of the literature was to identify etiologic factors that influence cognitive impairment as a precursor to dementia in individuals with diabetes. Physiological, psychological, and situational factors were recognized as important life course components of cognitive impairment in later adulthood. Developing interventions targeting modifiable factors is warranted in preventing cognitive impairment in adults with diabetes.

1. Introduction

Diabetes is a risk factor for dementia resulting from vascular or neurodegenerative changes [1]. In 2021, approximately 537 million people worldwide had diabetes, predicted to increase to 783 million people by 2045 [2]. Study indicates that 45% of adults with type 2 diabetes experience mild cognitive impairment, and this prevalence has been increasing as the world’s population ages [3]. Individuals with diabetes have a significantly higher likelihood of developing cognitive impairment and experiencing subjective cognitive decline (SCD) than individuals without diabetes [4,5]. Given that cognitive impairment precedes dementia [6], it is important to identify factors that predict cognitive impairment in individuals with diabetes.
Cognitive impairment in diabetes is defined as a loss of ability in major cognitive domains, such as memory, attention, processing speed, learning, and executive function [1]. Cognitive impairment can exacerbate conditions such as hearing loss, chronic pain, and physical disabilities [1]. Individuals with type 2 diabetes and cognitive impairment experience difficulties with concentration and attention, frequent forgetfulness, and slower processing speed [7]. SCD is one of the first symptoms of cognitive impairment [8], and it predicts worsening memory abilities and a faster rate of subsequent memory decline [9]. SCD may also interfere with one’s ability to participate in activities, such as taking medication [10].
Diabetes is related to cognitive impairment through pathophysiological mechanisms [11,12]. Chronic hyperglycemia and hypoglycemic events are risk factors for cognitive impairment and dementia in type 2 diabetes [12,13]. Hyperglycemia may hasten cognitive impairment by accelerating larger vessel disease and reducing capillary perfusion in the brain [14], and it may also affect multiple brain regions (i.e., white and gray matter in the frontal lobe) involved in cognitive performance [15]. Furthermore, insulin resistance in type 2 diabetes may affect insulin signaling and reception in the brain, which can accelerate cognitive impairment [16,17,18]. Individuals with poor glycemic control are at a high risk of memory impairment, decreased volume of the hippocampus [19], and cognitive decline [20].
Cognitive impairment in type 2 diabetes may negatively affect diabetes self-management. A significant negative correlation has been found between impairment of executive function and self-management in older adults with type 2 diabetes. Moreover, cognitive impairment can hamper the achievement of optimal glycemic control [21]. Patients with type 2 diabetes and cognitive impairment had significantly lower levels of self-management than those with type 2 diabetes who do not have cognitive impairment [22]. Specifically, patients with cognitive impairment are less likely to adhere to their diet and exercise regimens [23]. Consequently, cognitive impairment may lead to poor glycemic control, diabetes-related complications, and more frequent hospital admissions [24].
Controlling modifiable factors is central to preventing and slowing the progression of cognitive impairment and dementia in individuals with diabetes and avoiding severe diabetes-related complications. Thus, it is important to thoroughly examine the multiple factors contributing to SCD and cognitive impairment in diabetes. This is especially salient, noting that brain structure and cognitive impairment symptoms in individuals with diabetes across the lifespan may be influenced by multiple factors [25], not solely the presence of diabetes. However, studies have predominantly focused on disease-related factors, frequently overlooking the impact of an individual’s early life and situational factors surrounding individuals. Although prior studies have examined multiple factors (i.e., genetics, comorbidities, and depression) associated with cognitive impairment [26], there is limited literature using life course trajectory to examine factors of cognitive impairment in adults with diabetes. The purpose of this narrative review was to apply the theory of unpleasant symptoms from the life course perspective to better understand the association between multiple factors and cognitive impairment in individuals with diabetes. Furthermore, we aimed to identify the possible influencing factors contributing to SCD and cognitive impairment and to provide future directions for the amelioration of these concerns.

2. The Theory of Unpleasant Symptoms

The theory of unpleasant symptoms views the multiple factors that contribute to the experience of unpleasant symptoms and performance [27]. The theory encompasses three main components: (a) influencing factors (physiological, situational, and psychological factors), (b) unpleasant symptoms, and (c) performance.
Physiological influencing factors include genetic, disease-related, physiological, and anatomical variables (i.e., age, race/ethnicity, nutrition status, inflammation response attributable to infection, variation in energy or hormonal levels, and disease duration and stage). Psychological influencing factors encompass both cognitive and affective variables, including a person’s level of knowledge about their disease, mood, and affective state. Situational influencing factors include one’s social/physical environment (i.e., culture, access to social support/health care, socioeconomic status, lifestyle behaviors, family status, and occupation). All these factors are interrelated and can affect a person’s experience of unpleasant symptoms. The consequences of symptom experience could impact performance, which is one’s ability to perform or function cognitively, physically, and socially (Figure 1).

3. Life Course Perspective

According to the life course approach, the development of cognitive function is a dynamic process that is impacted by cumulative life experiences, and one’s health is shaped by adaptations made over the lifespan [28]. Cognitive function is formed by multiple factors operating across the life course, from prenatal to later adulthood [29]. The prenatal period is the starting point for people’s cognitive development, and the peak of cognitive functioning is reached in the mid-20s, followed by a decline that begins in middle adulthood (mid-40s), which is a critical point for comprehending the trajectory of cognitive functioning. Cognitive ability in later adulthood is affected by the accumulation of the influences of risk factors (i.e., environment, demographics, and lifestyle) throughout a person’s life [30]. Adults between 45 years and 65 years of age (middle adulthood) comprise the age group most frequently newly diagnosed with diabetes [31]; thus, middle adulthood is a crucial period for understanding the cognitive impairment trajectory because diabetes is an independent risk factor for cognitive impairment [1].
Taking a life course perspective on cognitive impairment may enhance preventive efforts [32]. Therefore, this study aimed to apply a life course perspective to the theory of unpleasant symptoms to better understand the trajectory of cognitive impairment in adults with diabetes. We identified potential influencing factors (i.e., physiological, psychological, and situational factors based on the theory of unpleasant symptoms) across four periods of the lifespan: the prenatal period, childhood to early adulthood, middle adulthood, and late adulthood that might contribute to cognitive impairment symptoms in middle and later life in patients with diabetes.

4. Physiological Factors and Cognitive Impairment

Recent studies have indicated that physiological factors, such as genetic factors, aging, sex, nutritional status, and diabetes comorbidities, are linked to a greater risk of cognitive impairment [1,17,33].

4.1. Apolipoprotein E (APOE) Gene

In the prenatal stage, a genetic predisposition toward cognitive decline may be established. Recent studies have reported a link between the APOE gene and cognitive impairment in patients with diabetes [34]. The literature indicates that APOE ε4 carriers exhibit poorer performance on a range of cognitive tasks in late adulthood, particularly tasks that assess executive function, global cognition, and memory [35,36,37,38]. The prevalence of Alzheimer’s dementia was found to be approximately 50% in individuals who were carriers of the APOE ε4 gene. Furthermore, there are differences between ethnic groups; the highest prevalence of the APOE ε4 carrier was found in people from Northern Europe and the lowest in those from Southern Europe and Asia [39]. Prior studies have also found a link between APOE and the risk of type 2 diabetes [40,41]. Moreover, the APOE E3/E4 genotype is a strong predictor of CVD in adults with type 2 diabetes [42]. The presence of the APOE e4 allele in adults with diabetes showed an increase in the development of dementia [33].

4.2. Aging

Middle adulthood has been characterized by cognitive decline, particularly related to executive function, processing speed, and learning [43]. The effects of aging on cognitive function are extensive and have several etiologies. The volume of the brain area, which is important in memory, decreases as people become older [44]. Additionally, the accumulation of the amyloid beta protein with aging can contribute to the loss of grey matter volume [45]. Amyloid beta and the loss of brain volume may be related to an increased risk of cognitive impairment over time [44]. Furthermore, the severity of SCD in memory function was found to be linked to the aggregation of amyloid beta plaques in the frontal cortex [46]. Middle-aged adults with diabetes could aggravate cognitive impairment. A large longitudinal cohort study among middle-aged adults demonstrated that individuals with type 2 diabetes experienced an accelerated cognitive decline than those without diabetes. Specifically, adults with type 2 diabetes exhibited a 45% faster decline in memory, 29% in reasoning, and 24% in global cognitive scores in 10 years compared with individuals without diabetes [47]. Duration of diabetes and glycemic control are major factors contributing to cognitive impairment in middle-aged adults with diabetes [47]. Similar findings were also reported in the community-based Atherosclerosis Risk in Communities (ARIC) Study among middle-aged adults [20].

4.3. Sex

The presence of sex differences may be associated with cognitive function in middle and later adulthood in patients with type 2 diabetes. To date, the impact of sex-specificity on cognitive impairment in patients with diabetes remains unclear. Evidence indicated that females with type 2 diabetes were more likely to have a higher risk of cognitive impairment and dementia than males with type 2 diabetes. A cross-sectional study found that the presence of diabetes was linked to an increased risk of brain atrophy in females but not in males [48]. Another study showed that females with type 2 diabetes were associated with worse cognitive function than males [49]. Additionally, a longitudinal study involving patients with type 2 diabetes found that females had an accelerated rate of cognitive decline partially mediated by depression compared with males [50].

4.4. Nutritional Status

Nutritional status, including obesity, malnutrition, and unintentional loss of body weight, is associated with cognitive impairment in adults with diabetes [51,52]. Nutritional state significantly correlates with cognitive function in older adults, and poor nutritional state has a strong correlation with cognitive deterioration [53]. Individuals with diabetes who gained more than 10% of weight were more likely to develop dementia than those who gained less than 5% of weight (Hazard ratios [HR] 1.4, 95% confidence interval [CI]: 1.1–1.8). Similarly, individuals with diabetes who lost more than 10% of their weight increased the risk of dementia incidence than those who lost less than 5% (HR 1.3, 95% CI: 1.1–1.6) [51].
Obesity has a strong association with cognitive impairment in patients with type 2 diabetes. Obesity is prevalent in individuals with type 2 diabetes, and it could lead to insulin resistance [54]. According to a cross-sectional study, higher body mass index (BMI) in adults aged 50 and over with type 2 diabetes was linked to poor cognitive function [49]. Furthermore, a longitudinal study in older adults with type 2 diabetes found that central fat distribution and total fat mass were associated with cognitive decline after a 2-year follow-up [55]. However, there is controversy surrounding the relationship between obesity and cognitive impairment in patients with type 2 diabetes. Some evidence suggests that obesity may have a protective effect against cognitive decline. A study demonstrated that obesity was associated with better cognitive function in adults with type 2 diabetes [56].

4.5. Diabetes Comorbidities

Individuals with type 2 diabetes have a high risk of developing diabetes-related comorbidities, such as cardiovascular disease (CVD) and kidney disease, that may affect cognitive impairment [57]. Poor glycemic control over the long term can lead to an increased prevalence of CVD in late adulthood [58]. Chronic hyperglycemia leads to oxidative stress and an inflammatory response, resulting in cell damage and dyslipidemia [59]. This, in turn, contributes to the formation of atherosclerotic plaques, leading to cardiovascular disease. CVD can influence cognitive impairment by accelerating brain aging and causing vascular brain injuries such as ischemia, hypoxic events, and blood-brain barrier leakage [18]. Older adults with diabetes are particularly at increased risk of developing CVD, which is a significant predictor of mild cognitive impairment [60]. According to a six-year observational study, severe systolic hypertension co-existing with diabetes significantly increased the risk of developing dementia and its subtypes, such as vascular dementia [61].
Reduced kidney function may increase the risk of cognitive impairment and dementia. For example, amyloid beta is typically cleared by the kidney or liver. However, poor kidney function can lead to inadequate clearance of amyloid beta [62]. Consequently, the accumulation of amyloid beta may contribute to the development of Alzheimer’s disease. A cross-sectional study among middle-aged adults with type 2 diabetes revealed that individuals with albuminuria demonstrated significantly lower scores in tests assessing executive function, memory, and processing speed than those without kidney disease [63]. Additionally, a study found that decreased estimated glomerular filtration rate and albuminuria were associated with abnormal brain magnetic resonance imaging and poor cognitive function in adults with type 2 diabetes [64].

5. Psychological Factors and Cognitive Impairment

Increasingly, evidence indicates that psychological factors are associated with cognitive impairment and SCD in individuals with diabetes. Negative emotional states (i.e., repeated stress exposure, depression, and anxiety) may be predictors of cognitive impairment and dementia in individuals with diabetes [65,66]. Among adults with SCD, 34% experienced mental distress, and mental health co-morbidities in diabetes are commonly associated with cognitive impairment [1]. Higher levels of depressive symptoms and anxiety are associated with more subjective memory decline [67].

Depressive and Anxiety Symptoms

Depressive and anxiety symptoms in both middle and later adulthood may affect SCD [68] and cognitive impairment in patients with diabetes [66]. The onset of depression in middle adulthood and depression in late adulthood has been associated with a greater risk of cognitive impairment [69,70]. Depressive symptoms are also strongly related to cognitive impairment in middle adulthood, late adulthood, and early adulthood [71]. Depression is associated with a high risk of CVD and the presence of vascular lesions on magnetic resonance images [72], which can lead to brain neuronal damage [73]. Depression may lead to hypothalamic–pituitary–adrenal axis dysregulation, resulting in increased glucocorticoid secretion, which hampers negative feedback. Increased cortisol levels can damage memory areas in the brain in patients with type 2 diabetes [74]. Anxiety may accelerate brain aging through the accumulation of beta-amyloid plaques, resulting in a faster rate of decline in cognitive function. Over a 10-year period, severe anxiety in mid-adulthood was linked to a greater risk of dementia [75]. Furthermore, high levels of anxiety can negatively affect attention and lead to cognitive impairment in late adulthood [76]. Adults with type 2 diabetes usually have a high prevalence of microvascular dysfunction, which impairs cerebral processes and contributes to cognitive impairment and depression [77]. A longitudinal study found that females had a higher tendency to experience depressive symptoms, and longer duration of diabetes and lower levels of education were linked to the presence of anxiety symptoms and cognitive impairment among individuals with type 2 diabetes [78].

6. Situational Factors and Cognitive Impairment

Considerable evidence indicates that situational factors can accelerate cognitive decline in late adulthood. Many recent studies have shown that social factors (i.e., socioeconomic status, marital status, educational level, lifestyle behaviors, and social relationships) are linked to a greater risk of cognitive impairment [17].

6.1. Socioeconomic Status (SES)

Low SES is a well-known influencing factor in cognitive impairment. Low SES may affect cognitive function through many mechanisms, including unhealthy dietary habits and physical inactivity [79]. A low level of education, occupation status, and low income were predictors of cognitive impairment in adults with type 2 diabetes [80]. Mounting data suggests that SES in early life can influence cognitive function in later adulthood [81]. For example, exposure to famine during childhood has been associated with impaired executive function in adulthood [82]. Additionally, individuals with a low SES in early life are more likely to experience environmental toxins, repeated stress, poor nutrition, and poor social relationships that could influence cognitive impairment in middle and later adulthood [83,84].
Education is regarded as one of the SES factors that influence cognitive function in later adulthood [85]. Higher educational attainment can be a dampening factor in the development of cognitive impairment in diabetes [86,87]. The association between educational attainment and cognitive impairment can be explained by the cognitive reserve theory, suggesting that mental stimulation in early life provides an extra capacity for cognition to compensate for cognitive decline in later adulthood [88]. Education level is negatively associated with cognitive impairment in older adults with diabetes. For example, older adults with type 2 diabetes who have completed tertiary education have a 95% lower risk of developing cognitive impairment than those with an education level below primary school [89]. Additionally, higher levels of education in early life are associated with a slower cognitive decline in later life, which is mediated by higher income [90]. Conversely, lower levels of education are related to a decline in cognitive function in older adults with diabetes [91,92,93].

6.2. Lifestyle Behaviors

Unhealthy behaviors, such as physical activity, smoking, and dietary habits, are regarded as the major modifiable factors in diabetes for mitigating progressive cognitive impairment [94]. Additionally, physical inactivity, smoking, and alcohol consumption are associated with SCD [95].

6.2.1. Smoking

Smoking is known to be associated with cognitive impairment, but the underlying mechanisms are unclear. It is believed that carbon monoxide present in tobacco smoke may interrupt the provision of oxygen to the brain, which could affect cognitive function through vascular pathways. Exposure to second-hand smoke during childhood is also related to cognitive impairment in middle and later adulthood [96,97]. Additionally, smoking may decrease insulin secretion and increase insulin resistance in adults with diabetes [98]. Nicotine may stimulate the secretion of hormones, such as growth hormone, catecholamines, and cortisol, which counteract the effects of insulin and increase insulin resistance [99]. Consequently, increased insulin resistance may lead to the accumulation of amyloid β-protein and abnormal tau phosphorylation, which subsequently increases the risk of Alzheimer’s disease [100].
Recent studies have shown that individuals who currently smoke cigarettes have a higher risk of developing mild cognitive impairment than those who do not smoke. Among adults with diabetes, current smokers have a 3.6 times higher risk of developing mild cognitive impairment than individuals who do not smoke [101]. Smokers also tend to suffer from SCD more than non-smokers in middle and later adulthood [95]. The long-term effects of smoking in terms of pack years can increase the risk of cognitive impairment and accelerate cognitive decline in people with diabetes, affecting global cognitive performance [101,102]. Specifically, each additional pack-year smoked was found to increase the likelihood of a speed-up four-year cognitive decline by 1% [102].

6.2.2. Physical Activity

Accumulating evidence indicates that physical activity plays a role as a protective factor against cognitive impairment. Adequate physical activity is associated with enhanced memory function [103]. Most of all, healthy eating and exercise habits can affect proper glycemic control, which, in turn, can positively affect cognitive function. Physical activity improves glycemic control by increasing insulin sensitivity and the use of glucose by the peripheral blood vessels [104]. Furthermore, moderate physical activity can influence cognitive function across the life course, including working memory, and can reduce simple reaction time [105]. In middle and later adulthood, individuals with diabetes with a higher physical activity level are more likely to have better memory function [106], while individuals experiencing SCD tend to have lower levels of physical activity [107]. Moreover, evidence suggests that higher physical activity has been linked to a larger hippocampal volume, and older adults with type 2 diabetes who participate in more moderate-to-vigorous physical activity tend to exhibit improved attention-processing speed [108].

6.2.3. Diet

In the prenatal stage, maternal undernutrition can lead to accelerated cognitive impairment in later adulthood [109]. Additionally, maternal gestational diabetes can increase the risk of type 2 diabetes and obesity in fetuses later in life [110]. Interestingly, patients with intrauterine exposure to diabetes tended to grow up to prefer high-fat and sweet foods [111]. Evidence shows that early-life dietary patterns are related to cognitive impairment in later life. For example, an unhealthy diet and obesity in early life can negatively affect psychological status and cognitive function [112]. In middle and later adulthood, poor diet, including the consumption of packaged foods and frequent alcohol use, are linked to cognitive impairment in individuals with type 2 diabetes [113]. Poor diet patterns can cause an increased risk of diabetes that leads to accelerated cognitive impairment. The Mediterranean diet, which is characterized by a reduced intake of meat and saturated fat and an increased intake of vegetables, fruits, and fish, can positively influence cognitive function, specifically verbal memory, in older adults [114]. Thus, healthy eating habits may be a protective factor against cognitive impairment in individuals with diabetes.

6.3. Social Relationship

A growing body of studies suggested that social relationships are considered influencing factors for progressive cognitive impairment. Some studies have reported that adversity in childhood (i.e., poor childhood relationships with parents and insufficient social support) can negatively influence cognitive impairment in middle and later adulthood [115,116]. This early-life stress causes brain changes associated with cognitive function [117] and can also indirectly affect cognitive impairment through negative emotions, such as depression [118].
Strong social support is linked to improved cognitive function and reduced cognitive impairment in later adulthood [119]. Interestingly, social engagement and family function can mitigate cognitive impairment in diabetes, as social networks may have positive impacts on cognitive functioning, and social engagement is related to a lower risk of cognitive impairment [120]. Individuals with larger social networks and more social engagement are more likely to have better diabetes self-management behaviors, which decrease the risk of diabetes-related cognitive impairment [121]; thus, there may be a pathway that associates social relationships and cognitive impairment. Moreover, adults who live alone but engage in social interaction (i.e., family, friends, and neighbors) less frequently tend to experience SCD in middle and later adulthood [95]. In individuals with diabetes, single marital status was shown to be associated with cognitive impairment, possibly because unmarried adults had fewer opportunities to interact and communicate with others [93].
Social relationships have both objective and subjective aspects, and each aspect is varied and complex [122]. Individuals who lack social relationships and social connections may experience loneliness, which has also been linked to cognitive impairment in middle and later adulthood [123]. Loneliness is defined as the subjectively perceived difference between an individual’s actual social relationships and their desired social relationships. It is distinct from social isolation, which is defined as an objective deficit of social interactions and ties [124]. Individuals who are lonely could experience emotional distress, such as depression and anxiety, leading to metabolic syndrome through poor health behaviors (i.e., a lack of physical activity participation and functional limitations) [125]. Loneliness can also have an impact on cognitive impairment through physical health problems, including increased systolic blood pressure [126]. Additionally, loneliness mediated the relationship between social isolation and SCD in late adulthood of diabetes and was significantly related to SCD [127]. However, since the evidence between loneliness and cognitive impairment in individuals with diabetes is still scarce, more studies are needed.
Taken together, multiple influencing factors may affect cognitive impairment in individuals with diabetes, and the accumulation of these factors can accelerate cognitive decline in later adulthood (Figure 2). Some factors are latent modifiable factors and thus may be targeted for intervention to slow or prevent the progression of cognitive impairment and dementia in patients with diabetes.

7. Discussion and Future Directions

The paper discusses the possible influencing factors that may contribute to SCD and cognitive impairment in individuals with type 2 diabetes across the lifespan, based on the theory of unpleasant symptoms. The life course approach framework is valuable for understanding these complex factors, as the degree to which they contribute to cognitive impairment risk in middle-aged and older adults with type 2 diabetes depends on the life course trajectory.
According to the life course theory, the development of cognitive reserve may be affected by one’s life and experiences, and the accumulation of risk factors has a significant impact on cognitive impairment in middle-aged and older adults [128]. The influencing factors guided by the theory of unpleasant symptoms discussed in this article may help develop interventions tailored to individual levels based on exposures and experiences across the life span. Identifying and controlling modifiable factors may help prevent the development of cognitive impairment and dementia in individuals with type 2 diabetes. This approach is consistent with the findings of a recent study on cognitive impairment in type 2 diabetes [113], which highlighted the importance of modifiable factors in preventive strategies for cognitive impairment in individuals with diabetes.
The theory of unpleasant symptoms predicates that the influencing factors may affect an individual’s performance (i.e., cognitive functioning, including executive function, memory and learning, motor function, and processing speed) through cognitive impairment symptoms [27]. One notable feature of this conceptual framework is that influencing factors and cognitive impairment symptoms affect cognitive functioning which can impact diabetes self-management. Effective executive function is significantly associated with the long-term performance of diabetes self-management behaviors [129], and cognitive impairment may lead to poor self-management behaviors, resulting in poor glycemic control [11,130], which further contributes to cognitive impairment. Thus, it is crucial to consider the relationship between influencing factors, cognitive impairment, and self-management in diabetes. In addition, healthcare providers must be aware of the association between poor diabetes self-management and cognitive impairment in middle-aged and older adults with type 2 diabetes. Despite the relationship between diabetes and cognitive impairment, most clinicians tend to overlook the diagnosis of cognitive impairment in individuals with type 2 diabetes [131]. Clinical assessment of cognitive impairment and clinical guidelines for older adults with type 2 diabetes are needed [132].
We present several future research directions based on our conceptual framework. First, interventions targeting modifiable influencing factors (i.e., lifestyle behaviors) should be developed to prevent cognitive impairment in middle-aged and older adults with diabetes. We recommend conducting longitudinal intervention studies that combine cognitive training and lifestyle changes in physical activity and healthy eating habits to improve cognitive ability and diabetes self-management behaviors. Second, future studies are needed to examine the potential pathways of the effect of cognitive impairment on diabetes self-management through mediating or moderating factors (i.e., physiological, psychological, and situational factors) in middle-aged and older adults with type 2 diabetes. Impaired memory and executive functions may negatively affect multiple aspects of diabetes self-management [130]. Little is known about the role of mediating factors in the association between cognitive impairment and diabetes self-management. However, psychological factors, such as depression, may play a crucial role in this relationship. Third, future studies directly targeting education on the links between cognitive impairment and diabetes for middle-aged adults and older adults with diabetes, particularly for patients with low SES, low educational attainment, and racial minority groups, are needed.
There are some limitations to this review. First, the theory of unpleasant symptoms does not include spiritual factors [133]. A systematic review examined the effects of religion and spirituality on cognitive ability and found that spirituality could protect against cognitive impairment in middle-aged and older adults [134]. Religious and spiritual factors may affect cognitive impairment through various mechanisms [135]. For instance, coping strategies promoted by spiritual and religious practices may positively affect mental health outcomes [134,136], which can affect the memory areas in the brain through reductions in cortisol levels [134]. In addition, spirituality and religion can protect against cognitive impairment by promoting social engagement activities, including praying, singing, and studying the Bible in a group setting [137]. Future studies should consider the role of spiritual factors in the prevention of cognitive impairment. Second, although the theory of unpleasant symptoms presumes that influencing factors interact with each other and all such factors are intertwined in each life course trajectory, this review does not systemically identify these interactions. For example, loneliness, social support, and depression in older adults are interrelated and influence each other [138,139]. In future studies, it will be necessary to closely examine the intricate relationships between influencing factors.
In contrast to a comprehensive systemic review, we aimed to present information in such a way to be easily comprehended by a reader who is not necessarily well-versed on the topic. Thus, the focus of this narrative review was to provide a succinct, best-evidence synthesis of the literature, only highlighting those articles that we trust conveyed the key points needing to be emphasized while striving for parsimony. This involved screening and condensing a vast array of data into a brief constructive critique to benefit the reader. We opted not to include a lengthy table outlining the various details of each study in the literature (e.g., author names, country of publication, institution, research design, sample size, advantages, and disadvantages) but rather refer interested readers to our carefully selected reference list or the various systematic reviews on the topic.

8. Conclusions

In this narrative review, we have applied a life course perspective to the theory of unpleasant symptoms, presented a conceptual framework based on the theory for addressing the development of cognitive impairment in type 2 diabetes, and discussed future directions. This paper identifies the influencing factors in cognitive impairment symptoms across four periods of the lifespan. Also, this paper demonstrates that multiple influencing factors, including physiological, psychological, and situational factors, may affect cognitive impairment in individuals with type 2 diabetes over the life course trajectory. Each of these variables should be considered in developing effective interventions to prevent dementia and slow cognitive decline. It is important to note that cognitive impairment in adults with type 2 diabetes is associated with diabetes self-management. Therefore, healthcare providers must understand the effect of cognitive impairment on self-management in individuals with type 2 diabetes.

Author Contributions

Conceptualization, B.K. and J.H.; investigation, B.K.; methodology, B.K. and J.H.; writing—original draft preparation, B.K.; writing—review and editing, J.T.E. and J.H.; validation, J.T.E. and J.H.; visualization, B.K.; supervision: J.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed.

Conflicts of Interest

The authors have no competing interest to declare.

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Figure 1. Conceptual framework of cognitive impairment based on the theory of unpleasant symptoms.
Figure 1. Conceptual framework of cognitive impairment based on the theory of unpleasant symptoms.
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Figure 2. A life course approach framework of cognitive impairment in type 2 diabetes.
Figure 2. A life course approach framework of cognitive impairment in type 2 diabetes.
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Kim, B.; Efird, J.T.; Hu, J. A Life Course Approach to Understanding Cognitive Impairment in Adults with Type 2 Diabetes: A Narrative Literature Review. Diabetology 2023, 4, 323-338. https://doi.org/10.3390/diabetology4030028

AMA Style

Kim B, Efird JT, Hu J. A Life Course Approach to Understanding Cognitive Impairment in Adults with Type 2 Diabetes: A Narrative Literature Review. Diabetology. 2023; 4(3):323-338. https://doi.org/10.3390/diabetology4030028

Chicago/Turabian Style

Kim, Bohyun, Jimmy T. Efird, and Jie Hu. 2023. "A Life Course Approach to Understanding Cognitive Impairment in Adults with Type 2 Diabetes: A Narrative Literature Review" Diabetology 4, no. 3: 323-338. https://doi.org/10.3390/diabetology4030028

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