82
VOLUME 11 NUMBER 2 • JUNE 2014
REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: Sherifa A Hamed
Department of Neurology and Psychiatry, Assiut University, Assiut, Egypt
Tel: +2 088 2371820
Fax: +2 088 2333327/+2 088 2332278
e-mail:
Originally published in
Int J Diabetol Vasc Dis Res
2013;
1
(8): 803
.
S Afr J Diabetes Vasc Dis
2014;
11
(2): 82–86
Diabetes mellitus and the brain: special emphasis on
cognitive function
SHERIFA A HAMED
Abstract
Diabetes mellitus (DM) is a major public health problem.
Cognitive deficits are common with DM which range from
subclinical or subtle to severe deficits such as dementia.
Both hypoglycaemia and hyperglycaemia are causes of
cognitive impairment with DM. In patients with DM, not only
severe hypoglycaemia but also recurrent mild or moderate
hypoglyacemiahavedeleterious effect on thebrain. Recurrent
mild/moderate hypoglycaemia is associated with intellectual
decline, reduced attention, impaired mental abilities and
memory deficits. Hypoglycaemia may result in abnormalities
of neuronal plasticity, synaptic weakening and scattered
neuronal death in the cerebral cortex and hippocampus.
Chronic hyperglycaemia in type 1 and type 2 DM is associated
with low IQ (verbal, performance and total) and abnormalities
in testing for different domains of cognitive function such as
verbal relations, comprehension, visual reasoning, pattern
analysis, quantitation, memory, learning, mental control,
psychomotor efficiency, mental and motor processing
speed and executive function. The suggested mechanisms
incriminated in the pathogenesis of hyperglycaemia-related
cognitive dysfunction include, macro- and microvascular
disease or vasculopathy, hyperlipidaemia, hypertension,
insulin resistance and hyperinsulinaemia, stress response,
direct toxic effect of chronic hyperglycaemia on the brain,
advanced glycation end-products, inflammatory cytokines
and oxidative stress. Hyperglycaemia causes oxidative
stress, amyloidosis, angiopathy, abnormal lipid peroxidation,
accumulation of
β
-amyloid and tau phosphorylation, neuro-
inflammation, mitochondrial pathology, apoptosis and
neuronal degeneration in the cortex and hippocampus.
Depression has been identified as a risk for accelerated
cognitive decline with DM. The knowledge that diagnosis at
an early age, frequency of hypoglycaemia, poor glycaemic
control and presence of risk factors negatively affect
cognitive functions in DM will have important implications
for treatment and research purposes.
Keywords:
diabetes mellitus, hypoglycaemia, insulin resistance,
cognition, vascular disease
Introduction
Diabetes mellitus (DM) is one of the most common and most
important metabolic diseases worldwide. The incidence and
prevalence of DM are increasing rapidly due to industrialisation,
inappropriate diet, sedentary lifestyle and increased obesity.
1
Hypoglycaemia, hyperlipidaemia and vascular diseases (such as
angiopathy, nephropathy and cardiovascular, cerebrovascular and
peripheral vascular diseases) are common complications of DM.
2
Cognitive deficits are common with DM, which range from
subclinical or subtle to severe deficits such as dementia. Cognition
refers to the set of integrated and inter-related mental processes
and systems involved in acquiring knowledge and comprehending,
storing, retrieving and using this knowledge to perform day-to-day
activities. Both hypoglycaemia and hyperglycaemia are causes of
cognitive impairment with DM.
3-39
Intellectual decline, impaired
mental abilities and memory deficits are common with recurrent
hypoglycaemic episodes.
3-10
Studies indicate that repetitivemild andmoderate hypoglycaemia
cause impairment in synaptic plasticity with inability to induce long-
term potentiation (LTP), which plays a crucial role in memory and
this contributes to cognitive impairment.
11,12
Recurrent moderate
hypoglycaemia results in scattered neuronal death in the cerebral
cortex
13,14
and hippocampus.
15
While severe hypoglycaemia results
in oxidative stress and widespread neuronal death in the cerebral
cortex and hippocampus.
16,17
With hyperglycaemia, low IQ and reduced performance on
various domains of cognitive function, including verbal relations,
comprehension, visual reasoning, pattern analysis, quantitation,
digit forward, digit backward, memory, mental control, associative
learning, psychomotor efficiency, problem solving, mental and
motor processing speed, eye–hand coordination and executive
function, are common.
18-26
Metabolic derangement, macro- and
microvascular complications,
27,28
oxidative stress
29,30
and diabetes-
related depression also occur.
31-35
Chronic hyperglycaemia causes oxidative stress, amyloidosis,
angiopathy, abnormal lipid peroxidation, increase in the formation
of advanced glycation end-products, accumulation of
β
-amyloid and
tau phosphorylation, neuro-inflammation, mitochondrial pathology,
apoptosis, neurodegeneration in the cortex and hippocampus and
brain atrophy.
36-39
This review was performed through a comprehensive search
in the PubMed, ISI web of science, Science Direct and Scopus
databases from 1990 to 2013, using the following search terms:
cognitive function in diabetes, hypoglycemia and cognition, type 1
DM (T1DM) and cognition and type 2 DM (T2DM) and cognition.
Data from epidemiological, longitudinal, prospective, double-
blinded and clinical trial studies and case reports were considered.
We also checked the reference lists of the retrieved studies for
additional reports.
In this review, we summarised the experimental and clinical
evidence of cognitive dysfunctionwith DM, the possiblemechanisms
underlying cognitive dysfunction in DM, the relationship between
