Diabetes, Alzheimer disease, and vascular dementia

Ahtiluoto, Satu; Polvikoski, Tuomo; Peltonen, Markku; Solomon, Alina; Tuomilehto, J.; Winblad, Bengt; Sulkava, Raimo; Kivipelto, Miia

doi:10.1212/wnl.0b013e3181f4d7f8

Cited by 414 publications

(341 citation statements)

References 31 publications

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“…We further postulated that BBB impairment might be a cause for this aggravation. These hypotheses were based on evidence showing that insulin resistance is linked with increased cognitive impairment (Ahtiluoto et al, 2010; Schnaider Beeri et al, 2004) and with the rationale that the association between insulin resistance and vascular disease (Semenkovich, 2006) could lead to vascular damage and to BBB abnormalities in the AD‐like mice model. To induce insulin resistance‐like phenotype, we fed WT and Tg mice with HFD (Surwit, Kuhn, Cochrane, McCubbin, & Feinglos, 1988) which, as expected, led to weight gain for both types of mice.…”

Section: Discussionmentioning

confidence: 99%

High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

et al. 2018

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Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood–brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high‐fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1–42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild‐type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.

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Section: Discussionmentioning

confidence: 99%

High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

et al. 2018

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“…(3) ... you took a break from reading a book or a text and when you returned to it you had serious difficulties in recalling what you had read or picking up where you had left off? (4) ... you had to think about what month it is?…”

Section: Resultsmentioning

confidence: 99%

“…Patients with type 2 diabetes mellitus have an increased risk for cognitive decline [1], for mild cognitive impairment [2], and for vascular as well as for Alzheimer's dementia [3][4][5][6]. A relationship between blood glucose levels and risk of dementia has been established…”

Section: Introductionmentioning

confidence: 99%

Glycilated Hemoglobin and Cognitive Impairment

Binder¹,

Marczak²,

Adler³

2017

Int J Neurol Neurother

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Objective: Hyperglycemia and type 2 diabetes mellitus have been shown to have a negative impact on cognitive performance in older adults. In order to assess the relevance of this effect in memory clinic patients, we examined the relationship between hyperglycemia and cognition in an unselected out-patient sample. Design:In a cross-sectional study in memory clinic patients, glycosylated hemoglobin (HbA1c) was determined and related to cognitive performance, subjective memory impairment, and self-perceived cognitive blackouts. Results:The frequency of mild cognitive impairment or mild dementia of the Alzheimer type was increased 1.7-fold in subjects with hyperglycemia. The HbA1c value was negatively correlated with global cognitive performance as well as with orientation, short-term memory and visuospatial capabilities. The frequency of cognitive blackouts was positively correlated with HbA1c levels and it was increased in hyperglycemic subjects.Conclusions: Hyperglycemia could be confirmed as a major risk factor for cognitive impairment. This could be shown even in a non-representative cross-sectional memory clinic sample. Thus, the HbA1c determination may be recommended for a routine diagnostic memory clinic work-up. KeywordsDiabetes mellitus, Hyperglycemia, HbA1c, Mild cognitive impairment, Dementia, Alzheimer, Subjective memory impairment, Cognitive blackouts, Memory clinic [7]. Even prediabetes and insulin resistance are associated with cognitive decline and brain atrophy [8].Diabetes may compromise cognitive function by various mechanisms, such as brain vascular lesions, insulin resistance, oxidative stress, the accumulation of advanced glycilation end products, inflammation or a competition of insulin and β-amyloid on the insulin-degrading enzyme [9].This may also apply to subjects with prediabetes as reflected by a moderately increased HbA1c level. Accordingly, it has been shown that the HbA1c value correlates with the rate of brain atrophy [10] and that it predicts conversion to dementia and mild cognitive impairment [11]. Glycosilated hemoglobin (HbA1c) is a measure of blood glucose concentration over the past two to three months and is used both for the diagnosis of diabetes and the assessment of diabetes management [12].We studied the effects of diabetes and hyperglycemia as determined by elevated HbA1c values on cognitive performance, subjective memory impairment and self-perceived cognitive blackouts in a group of patients of our memory clinic. Subjects and MethodsThe analyses were carried out in 113 patients consecutively presenting for the first time for memory assessment at our memory clinic. They were 70 women (61.9%) and 43 men (38.1%) at ages between 50 and 87 years (mean ± SD: 61.2 ± 9.1 years). Subjects with a history of neurological disorder, with an actual neurological or psychiatric disorder, or with a medication that may compromise cognitive performance were not

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“…Cardiac risk factors, in particular atrial fibrillation and congestive heart failure, have also been associated with the pathogenesis and progression of Alzheimer's disease [168][169][170][171][172][173][174][175][176][177].…”

Section: Association Between Cerebrovascular Disease and Alzheimer's mentioning

confidence: 99%

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

Alvarado¹,

Brito²,

Román³

et al. 2017

J Neurol Neurosci

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Cerebral vascular disease (CVD) represents the second cause in years of life lost, according to the Global Burden of Disease Study 2015 study. The global report on Alzheimer's disease 2015 estimates that in Latin America there are 9.2 million cases of dementia, with a prevalence of 8.2%. Undoubtedly, Alzheimer's disease is the most frequent cause, followed by vascular dementia (VD) with 15% of the cases, although global data are unknown in Latin America. Objective:To analyze and present the current evidence on the classification, pathophysiology, diagnosis and treatment of vascular cognitive impairment. Methodology:A group of experts met in Miami, Florida, in April 2016. The group included Neurologists, Geriatricians and Psychiatrists from the following countries: Mexico, Guatemala, El Salvador, Costa Rica, Peru, Spain, Bolivia, Chile, Paraguay, Colombia, Panama, Venezuela, Italy, the United States, Dominican Republic, Honduras and Nicaragua. The Delphi method was used to review available information (provided months before the meeting), in relation to assigned topics: definition of Cognitive Vascular Impairment (CVI), risk factors, pathophysiology, diagnosis (neuropsychological and imaging) and treatment. For the allocation of evidence and recommendation of available treatments, the GRADE system was used.The working groups analyzed and discussed available evidence on CVI concerning proposed definitions, risk factors and diagnostic elements. Subsequently, the conclusions of each of the working groups were drafted, which were reviewed by each of the authors and by the rest of the study groups until a global consensus was reached. Once this process was completed, the process of external validation and preparation of the final document was carried out.The results of this consensus allow the incorporation of the opinion and experience of physicians of different specialties in Latin America regarding the vascular cognitive impairment.

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Diabetes, Alzheimer disease, and vascular dementia

Abstract: Elderly patients with diabetes develop more extensive vascular pathology, which alone or together with AD-type pathology (particularly in APOE ε4 carriers) results in increased dementia risk.

Cited by 414 publications

References 31 publications

High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

Glycilated Hemoglobin and Cognitive Impairment

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

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