To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis.
The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects.
The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients.
In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores.
"Patients with T2D have a 2-to 3-fold higher risk of developing AD . Cognitive deterioration is more marked in patients with AD and T2D than AD alone . Furthermore, in patients with diabetes, the mean onset of dementia is 2 years earlier and survival outcomes are reported to be generally poorer . "
[Show abstract][Hide abstract] ABSTRACT: The senescence-accelerated mouse prone10 (SAMP10) strain, a model of aging, exhibits cognitive impairments and cerebral atrophy. We noticed that SAMP10/TaSlc mice, a SAMP10 substrain, have developed persistent glucosuria over the past few years. In the present study, we characterized SAMP10/TaSlc mice and further identified a spontaneous mutation in the Slc5a2 gene encoding sodium-glucose co-transporter (SGLT) 2. The mean concentration of urine glucose was high in SAMP10/TaSlc mice and increased further with advancing age, whereas other strains of senescence-accelerated mice, including SAMP1/SkuSlc, SAMP6/TaSlc and SAMP8/TaSlc or normal aging control SAMR1/TaSlc mice, exhibited no detectable glucose in urine. SAMP10/TaSlc mice consumed increasing amounts of food and water compared to SAMR1/TaSlc mice, suggesting the compensation of polyuria and the loss of glucose. Oral glucose tolerance tests showed decreased glucose reabsorption in the kidney of SAMP10/TaSlc mice. In addition, blood glucose levels decreased in an age-dependent fashion. The kidney was innately larger than that of control mice with no histological alterations. We examined the expression levels of glucose transporters in the kidney. Among SGLT1, SGLT2, glucose transporter (GLUT) 1 and GLUT2, we found a significant decrease only in the level of SGLT2. DNA sequencing of SGLT2 in SAMP10/TaSlc mice revealed a single nucleotide deletion of guanine at 1236, which resulted in a frameshift mutation that produced a truncated protein. We designate this strain as SAMP10/TaSlc-Slc5a2slc (SAMP10-ΔSglt2). Recently, SGLT2 inhibitors have been demonstrated to be effective for the treatment of patients with type 2 diabetes (T2D). SAMP10-ΔSglt2 mice may serve as a unique preclinical model to study the link between aging-related neurodegenerative disorders and T2D.
Biochemical and Biophysical Research Communications 10/2014; 454(1). DOI:10.1016/j.bbrc.2014.10.039 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline.
Participants were 889 community-dwelling 70-90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined.
All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7-49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine.
Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.
PLoS ONE 06/2013; 8(6):e65841. DOI:10.1371/journal.pone.0065841 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vascular risk factors (VRF) are associated with a higher incidence of dementia. However, the relationship with disease progression is unclear. This review examined the association of VRF (hypertension, hypercholesterolemia, diabetes mellitus, overweight, smoking or multiple VRF) and cognitive decline in patients suffering from dementia.
Literature was searched in four databases (Pubmed, Embase, Cochrane, PsychInfo) and 1779 articles were identified. This resulted in a total of 20 articles which were included.
Twelve studies on hypertension (HT) were inconsistent about the association with cognitive decline. For hypercholesterolemia (HC) 2 (out of 7) studies were associated with increased cognitive decline, as were both (2/2) studies which researched LDL-cholesterol. Articles were inconclusive about the effect of diabetes mellitus (DM): five (out of 13) found less cognitive decline, 2 found more cognitive decline, and 6 found no significant effect of DM. Overweight (BMI>25kg/m(2)) was associated in 2/4 studies with a slower rate of cognitive decline, while the other 2 studies found no effect. All studies (5/5) that researched smoking did not find a significant effect. Four studies (out of 7) that looked at multiple VRF found faster cognitive decline, and 3/7 found no effect.
The results of this review suggest an association between LDL-cholesterol and the progression of dementia, while inconsistent results were found for other VRF. Additional prospective cohort studies and experimental studies should be performed to better understand the causal contribution of VRF on cognitive decline in dementia.
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