Studies In Man Cognition And Dementia

Studies into the effects of diabetes on cognitive functioning in man can be broadly divided in two categories: case-control studies, which are mostly cross-sectional, and population-based surveys, which are often longitudinal. The case-control studies usually involved selected populations of patients and matched nondiabetic controls, using performance on a battery of neuropsychological tests as an outcome measure. Population-based surveys mostly involved elderly subjects, and used either relatively crude cognitive screening tests or a clinical diagnosis of dementia as a primary outcome measure.

Type 1 Diabetes in Children

Although quite a few studies have looked at neuropsychological test performance and school achievement in children with diabetes, this remains an area of some controversy (36). Some studies report that children with type 1 diabetes perform more poorly than control subjects on measures of intelligence, attention, processing speed, long-term memory, and executive skills (37,38), whereas other studies report that test performances are within the normal range (39). However, the observation that children with an early onset of diabetes (e.g., before the age of 6) are at increased risk for slowing of intellectual development is quite consistent (36,40). This increased vulnerability of younger children may be attributable to an increased sensitivity of the developing brain to the adverse effects of both hypo- and hyperglycemia (40,41).

Importantly, a recent study, involving a large population of patients and controls, reports that for most children, type 1 diabetes is not associated with lower academic performance compared with either siblings or classmates, although increased behavioral concerns are reported by parents (42). Apparently, the aforementioned subtle cognitive changes in children with type 1 diabetes do not significantly limit their functional academic abilities over time.

Type 1 Diabetes in Adults

All but a few studies on cognition in adult patients with type 1 diabetes have a cross-sectional case-control design. A recent meta-analysis of these studies shows that cognitive performance in patients with type 1 diabetes is characterized by a mild-to-moderate slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared (43).

However, uncertainty remains as to the disease variables that are related to impaired cognitive performance (43). This is likely to be largely because of methodological limitations of the studies that addressed this issue. Many factors other than diabetes, such as education, and genetic and socio-economic background, are important determinants of cognitive performance. This results in marked interindividual variation, which can easily obscure the effects of different diabetes-related variables in cross-sectional studies, particularly when sample sizes are relatively small, as is the case in the majority of the studies that have been published thus far. Longitudinal studies in which intraindi-vidual changes in cognition over time can be related to specific diabetes-related variables, would resolve this issue. Nevertheless, in cross-sectional studies lowered cognitive performance in diabetic patients appears to be associated with the presence of microvascular complications (44-46). Although cross-sectional studies generally report no consistent relation between diabetes duration and the severity of performance impairments (43), there are clear indications that the impairments are progressive over time (Fig. 1). Taken together, these data suggest that at least part of the cognitive changes observed in type 1 diabetic patients are because of chronic exposure to hyperglycemia, despite the fact that a relation between impaired cognition and increased HbA1 levels has not been reported (43).

In this context, the effect of hypoglycemia also needs to be addressed. The occurrence of episodes of severe hypoglycemia is an unwanted side effect of intensified insulin therapy (47). Several case reports and small case-control series indicate that repeated severe hypoglycemia may have permanent cognitive sequelae (43). In contrast, the largest available prospective survey on the consequences of severe hypoglycemic episodes on cognition in subjects receiving intensified insulin therapy does not show important negative effects (48). A recent meta-analysis of studies that compared type 1 diabetic patients with and without severe hypoglycemic episodes reached the same conclusion (43). Still, this issue warrants further investigation, as specific subgroups of patients, such as young children or subjects with advanced microvascular complications may be more susceptible to the adverse effects of hypoglycemia.

Type 2 Diabetes

Neuropsychological studies in type 2 diabetic patients report moderate degrees of cognitive impairment, particularly in tasks involving verbal memory or complex information processing (49,50). Tasks that assess basic attentional processes, motor reaction time, and immediate memory appear to be unaffected. This pattern of cognitive impairments is quite

Fig. 1. Psychomotor efficiency as measured with the Grooved Pegboard test (114) in patients with childhood onset type 1 diabetes. The curves are comprised of data that were collected in a number of cross-sectional studies of patients with diabeties (125 children and 189 adults) and demographically similar comparison subjects without diabeties (83 children and 184 adults). Data are presented as means ± SEM. Note that with increasing duration of diabetes (and increasing age) the relative difference between the two groups increases. Courtesy of Dr CM Ryan and coworkers (Western Psychiatric Institute and Clinic,University of Pittsburgh School of Medicine, Pittsburgh, PA), who conducted these studies. Part of these data has been published previously, i.e., refs. 44, 115.

Fig. 1. Psychomotor efficiency as measured with the Grooved Pegboard test (114) in patients with childhood onset type 1 diabetes. The curves are comprised of data that were collected in a number of cross-sectional studies of patients with diabeties (125 children and 189 adults) and demographically similar comparison subjects without diabeties (83 children and 184 adults). Data are presented as means ± SEM. Note that with increasing duration of diabetes (and increasing age) the relative difference between the two groups increases. Courtesy of Dr CM Ryan and coworkers (Western Psychiatric Institute and Clinic,University of Pittsburgh School of Medicine, Pittsburgh, PA), who conducted these studies. Part of these data has been published previously, i.e., refs. 44, 115.

different from that observed in type 1 diabetes. Moreover, the magnitude of the performance deficit, relative to age-matched controls, appears to be somewhat larger (Table 1).

Although, the risk of cognitive impairment in type 2 diabetes is well established, the underlying mechanisms remain largely unidentified. Type 2 diabetes typically develops in the context of a cluster of vascular and metabolic risk factors (including hypertension, dyslipidemia, and obesity), referred to as the "metabolic syndrome." The metabolic syndrome itself, with or without hyperglycemia, is associated with atherosclerotic cardiovascular disease, ischaemic stroke, and with cognitive decline and dementia (51). A key question is whether hyperglycemia per se or other factors from the metabolic syndrome lead to impaired cognition in type 2 diabetes. Previous studies indicate that increased HbA1 or fasting plasma glucose levels appear to be risk factors for cognitive dysfunction in type 2 diabetic patients (52). However, factors related to the metabolic syndrome are also likely to play a role, as elevated serum triglyceride levels are related to lower cognitive performance in type 2 diabetic subjects (53). Some investigators even suggest that cognitive dysfunction in type 2 diabetic patients is primarily because of concomitant hypertension (50). However, in the own cross-sectional survey on cognition in a population of 125 type 2 diabetic patients, hypertension had little effect on the nature and magnitude of cognitive impairment (54).

Age is probably a key factor in cognitive impairment in type 2 diabetic patients (54,55). In the above mentioned survey (54), age proved to be a strong predictor of impaired cognitive performance, much more so than in nondiabetic aged controls.

Table 1

An Overview of Changes in Cognition in Type 1 and Type 2 Diabetes

Cognitive domain

Type 1

Type 2

General intelligence Attention

Psychomotor speed

Verbal memory

Nonverbal memory

Mental flexibility-executive function

Visuospatial

Language

All About Alzheimers

All About Alzheimers

The comprehensive new ebook All About Alzheimers puts everything into perspective. Youll gain insight and awareness into the disease. Learn how to maintain the patients emotional health. Discover tactics you can use to deal with constant life changes. Find out how counselors can help, and when they should intervene. Learn safety precautions that can protect you, your family and your loved one. All About Alzheimers will truly empower you.

Get My Free Ebook


Post a comment