In simple terms, "cognitive" refers to the mental processes involved in thinking, knowing, and understanding. It's about how your brain takes in, processes, and uses information, covering everything from paying attention and remembering to learning, problem-solving, and using language.
7. Cognitive impairment during diabetes
Cognitive impairment is a frequent and important complication of diabetes and in some diabetic patients, dementia of various etiologies may develop.
A recent meta-analysis confirmed the association between diabetes and increased risk of cognitive impairment and dementia [61]. Mild cognitive impairment occurs in 37.5% - 53% of t2D patients [62-64] and severe cognitive impairment in 16% of t2D patients [65].
In type 1 diabetes patients aged over 60 years,
clinically important cognitive impairment was found in 48% [66].
The epidemiologic study based on 87 816 individuals aged 65 years or older with diabetes lasting for at least two years revealed that the risk of incidence of Alzheimer’s disease (AD) and related syndromes
was associated with poor diabetes monitoring and frequent diabetes complications [67].
The correlation between t2D and AD is complex. Common features characterizing t2D and AD are: insulin resistance, abnormal glucose metabolism in peripheral tissues, disturbed oxidative stress reactions, mitochondrial dysfunction, and insulin-mediated insulin transmission disorders, amyloid deposit aggregation, atrophy/neuronal
degeneration and cognitive dysfunctions [68-74]. In diabetic patients with AD, hyperphosphorylation of tau protein, amyloid ß (Aß) deposition disorders, higher levels of IL-6 in cerebrospinal fluid and more frequent ischemic changes in the central nervous system (CNS) caused by small blood vessel pathology than in non-diabetic AD patients are observed [75-77]. Of the many factors common to AD and t2D, insulin resistance is the one that most likely underlies AD [78-80].
In a cohort study encompassing 10 316 diabetics and 41 264 non-diabetic adult patients matched by sex and age adjusted HR for dementia was 1.47, indicating a higher risk of severe cognitive impairment among diabetics [81]. In this study, the coexistence of hypertension, hyperlipidemia, or both in the group of patients with diabetes did not further increase the risk of dementia. These findings indicated diabetes itself as the main cause of dementia risk. However, in the study encompassing 33 709 adult patients with diabetes and 67 066 patients without diabetes, matched by sex and age, observed for 10 years HR for dementia was 1.41 in the group of diabetic patients without hypertension, coronary artery disease, stroke, kidney disease or hyperlipidemia,
and 2.49 in the group of the patients with at least four of these comorbidities [82]. These data indicate a strong influence of vascular factors in the development of cognitive impairment in the course of diabetes.
The risk of development of cognitive impairment in
diabetic patients may be related to non-vascular and vascular causes [83, 84].
7.1. Non-vascular Causes of Dementia in the Course of Diabetes
7.1.1. Hypoglycemia
One of the non-vascular mechanisms leading to
cognitive impairment in the course of diabetes is hypoglycemia [66].
Studies conducted in animals indicate that mild/moderate
hypoglycemia in a relapsing manner (as occurs in patients using insulin therapy) may lead to cognitive impairment. This is due to the special sensitivity of the hippocampus structures, responsible for memorizing. Repeated episodes of hypoglycaemia induce the activation of oxidative stress reactions, which, among others, underlies
the damage of the CNS [85]. Severe hypoglycemia may be an important factor contributing to dementia, as shown by the study of 2001 diabetic patients. In the group of patients who previously experienced the episodes of severe hypoglycemia (3.1% of the patients studied) the risk of dementia was higher than in the remaining patients and in 1263 patients followed-up prospectively the risk of incident dementia associated with hypoglycemia HR was 2.54 [86]. In the hospitalized patients with type 1 diabetes and t2D, the individuals who have experienced episodes of hypoglycemia had poorer results in Mini-Mental State Examination than diabetic patients with no history of hypoglycemia [87]. However, the values close to the cut-off point, although differing statistically importantly, should be interpreted with caution. Animal studies allowed to find that recurrent mild hypoglycemia occurring in the course of the diabetes treatment might lead to cognitive impairment through mitochondrial and synapse injury [88].
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