Cognitive decline

About: Cognitive decline is a research topic. Over the lifetime, 29308 publications have been published within this topic receiving 1174689 citations.

Cognitive stimulation to improve cognitive functioning in people with dementia

Abstract: Background Cognitive stimulation is an intervention for people with dementia which offers a range of enjoyable activities providing general stimulation for thinking, concentration and memory usually in a social setting, such as a small group. Its roots can be traced back to Reality Orientation (RO), which was developed in the late 1950s as a response to confusion and disorientation in older patients in hospital units in the USA. RO emphasised the engagement of nursing assistants in a hopeful, therapeutic process but became associated with a rigid, confrontational approach to people with dementia, leading to its use becoming less and less common. Cognitive stimulation is often discussed in normal ageing as well as in dementia. This reflects a general view that lack of cognitive activity hastens cognitive decline. With people with dementia, cognitive stimulation attempts to make use of the positive aspects of RO whilst ensuring that the stimulation is implemented in a sensitive, respectful and person-centred manner. There is often little consistency in the application and availability of psychological therapies in dementia services, so a systematic review of the available evidence regarding cognitive stimulation is important in order to identify its effectiveness and to place practice recommendations on a sound evidence base. Objectives To evaluate the effectiveness and impact of cognitive stimulation interventions aimed at improving cognition for people with dementia, including any negative effects. Search methods The trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Group Specialized Register, called ALOIS (updated 6 December 2011). The search termsused were: cognitive stimulation, reality orientation, memory therapy, memory groups, memory support, memory stimulation, global stimulation, cognitive psychostimulation. Supplementary searches were performed in a number of major healthcare databases and trial registers to ensure that the search was up to date and comprehensive. Selection criteria All randomised controlled trials (RCTs) of cognitive stimulation for dementia which incorporated a measure of cognitive change were included. Data collection and analysis Data were extracted independently by two review authors using a previously tested data extraction form. Study authors were contacted for data not provided in the papers. Two review authors conducted independent assessments of the risk of bias in included studies. Main results Fifteen RCTs were included in the review. Six of these had been included in the previous review of RO. The studies included participants from a variety of settings, interventions that were of varying duration and intensity, and were from several different countries. The quality of the studies was generally low by current standards but most had taken steps to ensure assessors were blind to treatment allocation. Data were entered in the meta-analyses for 718 participants (407 receiving cognitive stimulation, 311 in control groups). The primary analysis was on changes that were evident immediately at the end of the treatment period. A few studies provided data allowing evaluation of whether any effects were subsequently maintained. A clear, consistent benefit on cognitive function was associated with cognitive stimulation (standardised mean difference (SMD) 0.41, 95% CI 0.25 to 0.57). This remained evident at follow-up one to three months after the end of treatment. In secondary analyses with smaller total sample sizes, benefits were also noted on self-reported quality of life and well-being (standardised mean difference: 0.38 [95% CI: 0.11, 0.65]); and on staff ratings of communication and social interaction (SMD 0.44, 95% CI 0.17 to 0.71). No differences in relation to mood (self-report or staff-rated), activities of daily living, general behavioural function or problem behaviour were noted. In the few studies reporting family caregiver outcomes, no differences were noted. Importantly, there was no indication of increased strain on family caregivers in the one study where they were trained to deliver the intervention. Authors' conclusions There was consistent evidence from multiple trials that cognitive stimulation programmes benefit cognition in people with mild to moderate dementia over and above any medication effects. However, the trials were of variable quality with small sample sizes and only limited details of the randomisation method were apparent in a number of the trials. Other outcomes need more exploration but improvements in self-reported quality of life and well-being were promising. Further research should look into the potential benefits of longer term cognitive stimulation programmes and their clinical significance.

Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease

Abstract: Vascular dysfunction has a critical role in Alzheimer’s disease (AD). Recent data from brain imaging studies in humans and animal models suggest that cerebrovascular dysfunction may precede cognitive decline and onset of neurodegenerative changes in AD and AD models. Cerebral hypoperfusion and impaired amyloid β-peptide (Aβ) clearance across the blood–brain barrier (BBB) may contribute to the onset and progression of dementia AD type. Decreased cerebral blood flow (CBF) negatively affects the synthesis of proteins required for memory and learning, and may eventually lead to neuritic injury and neuronal death. Impaired clearance of Aβ from the brain by the cells of the neurovascular unit may lead to its accumulation on blood vessels and in brain parenchyma. The accumulation of Aβ on the cerebral blood vessels, known as cerebral amyloid angiopathy (CAA), is associated with cognitive decline and is one of the hallmarks of AD pathology. CAA can severely disrupt the integrity of the blood vessel wall resulting in micro or macro intracerebral bleedings that exacerbates neurodegenerative process and inflammatory response and may lead to hemorrhagic stroke, respectively. Here, we review the role of the neurovascular unit and molecular mechanisms in vascular cells behind AD and CAA pathogenesis. First, we discuss apparent vascular changes, including the cerebral hypoperfusion and vascular degeneration that contribute to different stages of the disease process in AD individuals. We next discuss the role of the low-density lipoprotein receptor related protein-1 (LRP), a key Aβ clearance receptor at the BBB and along the cerebrovascular system, whose expression is suppressed early in AD. We also discuss how brain-derived apolipoprotein E isoforms may influence Aβ clearance across the BBB. We then review the role of two interacting transcription factors, myocardin and serum response factor, in cerebral vascular cells in controlling CBF responses and LRP-mediated Aβ clearance. Finally, we discuss the role of microglia and perivascular macrophages in Aβ clearance from the brain. The data reviewed here support an essential role of neurovascular and BBB mechanisms in contributing to both, onset and progression of AD.

Cognitive Profiles of Patients with Mild Cognitive Impairment or Dementia in Alzheimer's or Parkinson's Disease

Abstract: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are associated with severe cognitive decline, but it is still unclear to what extent they become functionally more similar over time. Methods: We compared amnestic mild cognitively impaired (aMCI; n = 29) patients to mild cognitively impaired (MCI) PD patients (n = 25), and patients with AD (n = 34) to patients with PD dementia (PDD; n = 15) with respect to cognitive functioning and mood. Results: aMCI patients were impaired in episodic memory, while MCI PD patients showed deficits in visuoconstruction and attention. AD and PDD patients showed comparable deficits on tests for language, attention and visuoconstruction. However, unlike PDD patients but similar to aMCI patients, AD patients showed a characteristic memory impairment, especially commission errors on recognition tasks, whereas PDD patients scored higher on the depressive mood questionnaire. Conclusions: In advanced stages of both diseases, the pattern of functional deficits associated with parietal and temporal lobe functions (attention, visuoconstruction and language) is similar. However, specific differences, already present in the early stage (recognition errors in AD, associated with mediobasal temporal lobe functioning, and depressed mood in PDD, associated with non-motor basal ganglia loops), are also observed in the late stage.

Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline

Abstract: Cellular senescence, which is characterized by an irreversible cell-cycle arrest1 accompanied by a distinctive secretory phenotype2, can be induced through various intracellular and extracellular factors. Senescent cells that express the cell cycle inhibitory protein p16INK4A have been found to actively drive naturally occurring age-related tissue deterioration3,4 and contribute to several diseases associated with ageing, including atherosclerosis5 and osteoarthritis6. Various markers of senescence have been observed in patients with neurodegenerative diseases7–9; however, a role for senescent cells in the aetiology of these pathologies is unknown. Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that the MAPTP301SPS19 mouse model of tau-dependent neurodegenerative disease10 accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of these cells as they arise using INK-ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary tangle deposition, and degeneration of cortical and hippocampal neurons, thus preserving cognitive function. Pharmacological intervention with a first-generation senolytic modulates tau aggregation. Collectively, these results show that senescent cells have a role in the initiation and progression of tau-mediated disease, and suggest that targeting senescent cells may provide a therapeutic avenue for the treatment of these pathologies. In a mouse model of tau-dependent neurodegenerative disease, the clearance of senescent glial cells prevents the degeneration of cortical and hippocampal neurons and preserves cognitive function.