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From mild cognitive impairment to dementia

100%

Gabryelewicz T.

Acta Neurobiologiae Experimentalis

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2011

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tom 71

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nr 1

The significance of cognitive decline in the elderly has been widely discussed in the literature. In particular, complaints of memory impairment are common in the elderly and were found in 80% of various community samples. Different approaches have been proposed to describe this decline and its relationship with the development of dementia. Unfortunately, the difficulty in disentangling “normal”, purely age-associated cognitive changes from changes related to early degenerative or vascular diseases has resulted in a lack of agreement on terminology and specific diagnostic criteria. Although there are a number of different definitions of mild cognitive deficits, the general concept is of a subjective memory impairment, and/or another domain in the context of cognitive impairment relative to age-matched controls and yet showing no loss of function and no dementia. Mild cognitive impairment (MCI) is a heterogeneous group with a variety of clinical outcomes. Most of the subjects will convert to dementia, but some MCI may never progress to any significant extent or even improve. The field of MCI research is currently focusing on identifying the risk factors of disease progression for the purpose of early therapeutic intervention, which may in turn delay or even prevent the onset of dementia. Individuals with a MCI are at an increased risk of developing dementia ranging from 3% to 15% per year. The prevalence of MCI varies from 15 to 30% of the population. Most of the studies demonstrate the age-dependent increase of MCI prevalence.

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Dementia and depression - whether the senescence has to look like that?

100%

Gabryelewicz T.

Acta Neurobiologiae Experimentalis

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2009

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tom 69

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nr 3

Dementia is a neurological condition manifested by reduced cognitive and psychological functioning, altered behaviour and decreased autonomy for social and professional performance in activities of daily living. Dementia is one of the most important causes of disability in the elderly. The number of dementia patients is increasing, as the population is growing older. Recent epidemiological evidence suggested a 2001 prevalence of 24.3 million cases of dementia worldwide. Alzheimer’s disease (AD) remains the most common cause of dementia, responsible for 60–70% of cases in Europe. There are 4.6 million new cases of dementia reported every year – that’s one new case every 7 seconds. Patients with AD gradually lose the ability to function independently and interest in life and many experience changes in personality, social withdrawal, uninhibited behaviour, and psychotic symptoms such as delusions, hallucinations and aggressive behaviour. The associated likely impact on the health and quality of life of persons with AD, their families, and societal healthcare and welfare resources, have led many authors to describe the condition as a “ticking bomb”. The depression prevalence in later life is 8 to 15%. Suicide in the elderly represents an immensely important and often overlooked medical problem. Based on its many distinct features, age-specifi c risk factors could be identifi ed. Proper diagnosis and treatment of affective disorders – contributing greatly to the pathogenesis of suicide in the elderly – could lead to a major decline in the suicide rate in this population.

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Alterations in apoptotic signaling in lymphocytes of patients in early stage of Alzheimer's disease precede massive neuronal loss in the brain

39%

Wojsiat J., Laskowska-Kaszub K., Mandecka M., Gabryelewicz T., Kuznicki J., Wojda U.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr Supl.

BACKGROUND AND AIMS: Alzheimer’s disease (AD) is the most common age-related dementia worldwide of unclear early pathogenesis. Mild Cognitive Impairment (MCI) represents an early AD stage, preceding massive deposition of Aβ aggregates and associated neuronal loss in the brain. Recently we demonstrated that sporadic AD (SAD) lymphoblasts show increased levels of p21 protein, the key regulator of G1/S cell cycle checkpoint and apoptosis (Bialopiotrowicz et al. 2011, Neurobiol Aging). In the current study we aimed to elucidate if p21 levels are altered early in AD, in lymphocytes of MCI patients, and to investigate the effects of p21 on the apoptotic response of SAD and MCI lymphocytes METHODS: We compared apoptotic response to 2 deoxy-D ribose (2dRib) in EBV-immortalized B-lymphoblasts from 16 patients with SAD, 17 patients with MCI and 10 age-matched healthy individuals without dementia. Apoptotic response was measured using flow cytometry assays: AnnexinV, mitochondrial membrane potential, and SubG1-phase. RESULTS: Comparing to controls, under basal conditions p21 levels assessed by immunoblotting were significantly elevated in MCI lymphoblasts, similarly as in SAD cells. 24 h after 2dRib treatment, apoptosis was higher in SAD cells than in controls, and after stimulation p21 decreased significantly in SAD and MCI cells. CONCLUSIONS: SAD lymphoblasts are significantly lessresistant to oxidative apoptotic stimuli than controls. In MCI lymphoblasts there were similar tendencies but without statistical significance. These results suggest that changes in the p21 levels and in apoptotic response in lymphocytes appear early in AD and gradually increase with the disease progression. Furthermore, our data indicate that lymphocytes may be useful for the development of new early AD diagnostic markers based on apoptotic regulatory proteins such as p21. This research was supported by the grant 2/BIOMARKAPD/ JPND/2012 and by the Nencki Institute statutory funds.

Ograniczanie wyników

3 Acta Neurobiologiae Experimentalis

3 Gabryelewicz T.

1 Kuznicki J.

1 Laskowska-Kaszub K.

1 Mandecka M.

1 Wojda U.

1 Wojsiat J.

1 2015

1 2011

1 2009

From mild cognitive impairment to dementia

Dementia and depression - whether the senescence has to look like that?

Alterations in apoptotic signaling in lymphocytes of patients in early stage of Alzheimer's disease precede massive neuronal loss in the brain