Sokratis G. Papageorgiou

A review of physical and cognitive interventions in aging.

Maintaining a healthy brain is a critical factor for the quality of life of elderly individuals and the preservation of their independence. Challenging aging brains through cognitive training and physical exercises has shown to be effective against age-related cognitive decline and disease. But how effective are such training interventions? What is the optimal combination/strategy? Is there enough evidence from neuropsychological observations, animal studies, as well as, structural and functional neuroimaging investigations to interpret the underlying neurobiological mechanisms responsible for the observed neuroplasticity of the aging brain? This piece of work summarizes recent findings toward these questions, but also highlights the role of functional brain connectivity work, an emerging discipline for future research in healthy aging and the study of the underlying mechanisms across the life span. The ultimate aim is to conclude on recommended multimodal training, in light of contemporary trends in the design of exergaming interventions. The latter issue is discussed in conjunction with building up neuroscientific knowledge and envisaged future research challenges in mapping, understanding and training the aging brain.

Current and future treatments for Alzheimer’s disease:

Alzheimer’s dementia (AD) is increasingly being recognized as one of the most important medical and social problems in older people in industrialized and non-industrialized nations. To date, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance. Three cholinesterase inhibitors (CIs) are currently available and have been approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist. Treatments capable of stopping or at least effectively modifying the course of AD, referred to as ‘disease-modifying’ drugs, are still under extensive research. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review we discuss current symptomatic treatments and new potential disease-modifying therapies for AD that are currently being studied in phase I–III trials.

A normative study of the trail making test A and B in Greek adults.

The purpose of this study was to explore the effects of age and education on the performance of the Trail Making Test (TMT), and to provide normative data in the Greek population. The TMT was administered to 643 healthy participants. All participants satisfied the criteria excluding dementia and other medical, psychiatric, and neurological disorders. Statistical analysis revealed that, age, education, and general level of intelligence significantly influence individual performance. Performance on TMT, especially part B, decreases with increasing age and lower levels of education. Current norms of the Greek version of TMT represent a useful set of norms for clinical practice.

Nonepisodic memory deficits in amnestic MCI

ObjectiveTo (a) compare patients with amnestic Mild Cognitive Impairment (MCI), mild Alzheimer disease (AD), and a group of healthy elderly persons on nonepisodic memory measures; (b) examine which measures are independent of level of education in the groups studied. BackgroundEpisodic memory impairment is a cardinal feature of preclinical AD. However, a number of other cognitive measures are also sensitive to the preclinical stage of AD and deficits in multiple domains characterize AD several years before clinical diagnosis. Materials and MethodsPatients with amnestic MCI (N=31), patients with mild probable AD (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory tasks measuring fluid intelligence, working memory, processing speed, verbal fluency, and visual-perceptual and motor functions. Amnestic MCI patients were selected based on clinical criteria and a subgroup was also selected based on psychometric criteria. ResultsMultivariate analyses of covariance, controlling for the effects of age, education, and sex, showed that fluid intelligence, working memory, processing speed, semantic fluency, visual-perceptual function, and complex motor function were significantly worse in the MCI than the elderly control group. Working memory, processing speed, semantic fluency, and complex motor tasks were significantly worse in the mild probable AD than the MCI group. The analyses were corroborated using the psychometrically derived MCI group. Conclusions(a) Performance on multiple nonepisodic memory measures is affected in the preclinical stage of AD, indicating that broad cognitive impairment characterizes that stage. (b) Complex motor tasks were independent of level of education in our sample, and may have practical utility in the early detection of dementia.

Structural and Functional Impairment of the Retina and Optic Nerve in Alzheimer’s Disease

PURPOSE The purpose of this study was to evaluate the macular and retinal nerve fiber layer (RNFL) thickness, and the electrical activity of the macula in patients with Alzheimers disease (AD). MATERIAL AND METHODS 30 patients with AD and 30 age and sex matched healthy controls were studied. The thickness and the electrical activity of the macula were evaluated by means of optical coherence tomography (OCT) and multifocal-electroretinogram (mf-ERG). RESULTS Visual acuity, as well as visual fields and colour vision testing of all patients were normal. However, the mean foveal thickness was 148.50 μm (vs. 171.50 μm in the control group, p=0.001) and the RNFL thickness was 104.5 μm in the superior area (vs 123 μm in the control group, p < 0.0001) and 116.5 μm in the inferior area (vs. 138 μm in the control group, p < 0.0001) around the optic nerve. The mean P1 response density amplitude of the foveal area was 146.50 nV/deg2 (vs. 293 nV/deg2 in the control group, p < 0.0001) and the perifoveal area was 56.60 nV/deg2 (vs. 81.50 nv/deg2 in the control group, p < 0.001). CONCLUSION Our study showed that in patients with AD, even without visual failure there was a decrease in macular and RNFL thickness, as well as a decrease of the electrical activity of the macula.

Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration.

BackgroundCerebrospinal fluid (CSF) biomarkers have been increasingly studied in dementia clinical and differential diagnosis. MethodsWe assessed levels of total tau protein (τT), tau phosphorylated at threonine 181 (τP-181), and β-amyloid1-42 (Aβ42) in 34 patients with frontotemporal lobar degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL). Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for measurements. ResultsTotal τ was significantly increased and Aβ42 decreased in FTLD and AD patients as compared with CTRL. CSF τP-181 levels were significantly increased only in AD. The τT/Aβ42 ratio successfully discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity, whereas the τT alone was more specific (95.7%) but less sensitive (64.75%). For the discrimination of FTLD from AD, τT/Aβ42 ratio was better (90.3% sensitivity and 64.5% specificity) compared with the other biomarkers alone or in combination, whereas τP-181 was less sensitive but more specific (68.4% and 85.7%, respectively). Subtype analysis revealed that the most AD-like profile of biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD profile were observed in patients with primary progressive aphasia. ConclusionsCombined analysis of CSF biomarkers may be useful for the best possible antemortem discrimination of FTLD from AD.

Gains in cognition through combined cognitive and physical training: the role of training dosage and severity of neurocognitive disorder.

Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen’s d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population

Although the first mutation associated with Parkinsons disease (PD) was identified several years ago in the alpha‐synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population.

The effects of a computer-based cognitive and physical training program in a healthy and mildly cognitive impaired aging sample

Objectives: The Long Lasting Memories (LLM) program concerns a newly integrated platform which combines cognitive exercises with physical activity within the context of advanced technologies. The main objective of this study was to present the preliminary results that determine the possible effectiveness of the LLM program in the improvement of cognitive functions and symptoms of depression in healthy elderly and subjects with mild cognitive impairment (MCI). Method: Fifty healthy and MCI subjects participated in the study. All of them received one hours physical training and 35 minutes’ cognitive training, 3 times a week, during the 12 weeks of the program. Before and after the intervention all participants were assessed using a battery of neuropsychological tests.Results: The results showed a significant improvement after the LLM training in global cognitive function, in verbal memory, in attention, in episodic memory and symptoms of depression. Conclusion: This study indicates that LLM is a promising solution for older adults with and without cognitive impairment, maintaining their wellbeing with few professional and technical requirements.

Time-frequency analysis methods to quantify the time-varying microstructure of sleep EEG spindles: Possibility for dementia biomarkers?

The time-varying microstructure of sleep EEG spindles may have clinical significance in dementia studies and can be quantified with a number of techniques. In this paper, real and simulated sleep spindles were regarded as AM/FM signals modeled by six parameters that define the instantaneous envelope (IE) and instantaneous frequency (IF) waveforms for a sleep spindle. These parameters were estimated using four different methods, namely the Hilbert transform (HT), complex demodulation (CD), matching pursuit (MP) and wavelet transform (WT). The average error in estimating these parameters was lowest for HT, higher but still less than 10% for CD and MP, and highest (greater than 10%) for WT. The signal distortion induced by the use of a given method was greatest in the case of HT and MP. These two techniques would necessitate the removal of about 0.4s from the spindle data, which is an important limitation for the case of spindles with duration less than 1s. Although the CD method may lead to a higher error than HT and MP, it requires a removal of only about 0.23s of data. An application of this sleep spindle parameterization via the CD method is proposed, in search of efficient EEG-based biomarkers in dementia. Preliminary results indicate that the proposed parameterization may be promising, since it can quantify specific differences in IE and IF characteristics between sleep spindles from dementia subjects and those from aged controls.