[show abstract][hide abstract] ABSTRACT: Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy. In fact, diabetes subjects are more prone to develop extense and earlier-than-usual leukoaraiosis (White Matter High-Intensity Lesions - WMHL). WMHL are usually present at different degrees in brain scans of elderly people. People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia. Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.
Biochimica et Biophysica Acta 01/2009; 1792(5):432-43. · 4.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pulmonary artery sarcoma is a rare and highly lethal disease whose clinical findings are often indistinguishable from those of chronic thromboembolic pulmonary hypertension. Partial improvement after thrombolytic therapy has suggested that thromboembolic phenomena may be superimposed on the tumor, but, to date, a well-documented statement of these events has not been provided.
Pathology - Research and Practice 02/2008; 204(2):139-41. · 1.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Metabolic syndrome (Met.S) consists of a conglomeration of obesity, hypertension, glucose intolerance, and dislipidemia. Frontal-subcortical geriatric syndrome (FSCS) is caused by ischemic disruption of the frontal-subcortical network. It is unknown if Met.S is associated with FSCS.
We evaluated 422 community-dwelling elderly (> or =60) in Brazil. FSCS was defined as the presence of at least one frontal release sign (grasping, palmomental, snout, or glabellar) plus coexistence of > or =3 the following criteria: (1) cognitive impairment, (2) late-onset depression, (3) neuromotor dysfunction, and (4) urgency incontinence. All values were adjusted to age and gender.
Met.S was present in 39.3% of all subjects. Cases without any of the FSCS components represented 37.2% ('successful neuroaging' group). People with 1-3 of the FSCS components ('borderline pathological neuroaging' group) were majority (52.6%), whereas those with 4-5 of these components (FSCS group) were minority (10.2%). Met.S was significantly associated with FSCS (OR=5.9; CI: 1.5-23.4) and cognitive impairment (OR=2.2; CI: 1.1-4.6) among stroke-free subjects. Number of Met.S components explained 30.7% of the variance on the number of FSCS criteria (P<0.001). If Met.S were theoretically removed from this population, prevalence of FSCS would decline by 31.6% and that of cognitive impairment by 21.4%.
Met.S was significantly associated with a 5.9 and 2.2 times higher chance of FSCS and cognitive impairment, respectively. Met.S might be a major determinant of 'successful' or 'pathological' neuroaging in western societies.
Neurobiology of aging 11/2007; 28(11):1723-36. · 5.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Metabolic syndrome (Met.S) is a risk factor for stroke, dementia, and ischemic heart disease (IHD). It is unclear whether Met.S is an independent risk factor for functional dependence, depression, cognitive impairment, and low health-related quality of life (HRQoL) in a population free of clinical stroke.
Two communities in southern Brazil.
Four hundred twenty people aged 60 and older.
An adapted (body mass index > or =30 kg/m(2) and blood pressure > or =140/90) Adult Treatment Panel III definition was used in diagnosing Met.S. Depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised) and Mini-Mental State Examination were evaluated along with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). HRQoL was measured using a visual analogue scale (0-10). All values were adjusted for age, sex, and presence of IHD.
Forty (9.5%) subjects had a stroke and were excluded from the final analysis. Met.S was present in 37.4% of the stroke-free population. Met.S was significantly and independently associated with 2.24 times as much ADL dependence, 2.39 times as much IADL dependence, a 2.12 times higher risk of depression, a 2.27 times higher likelihood of cognitive impairment, and a 1.62 times higher chance of low self-perceived HRQoL (all P<0.05). Adjustment for its own components reduced the strength of the above associations but did not eliminate their statistical significance. If Met.S were removed from this population, dependence, depression, cognitive impairment, and low QoL would be reduced 15.0% to 21.4%.
Met.S was significantly associated with functional dependence, depression, cognitive impairment, and low HRQoL, and its effects were independent of clinical stroke, IHD, and its own individual components.
Journal of the American Geriatrics Society 04/2007; 55(3):374-82. · 3.98 Impact Factor