Can Traditional Board Games Prevent or Slow Down Cognitive Impairment? A Systematic Review and Meta-Analysis
Authors: Pozzi, Federico Emanuele | Appollonio, Ildebrando | Ferrarese, Carlo | Tremolizzo, Lucio
Article Type: Systematic Review
Abstract: Background: Traditional board games can entail significant skills encompassing several cognitive functions across different domains. Therefore, they may potentially represent effective cognitive interventions in the aging population with or without Alzheimer’s disease or other types of dementia. Objective: We aimed at verifying the hypothesis that traditional board games can prevent or slow down cognitive decline, through a systematic review on traditional board games and dementia. Methods: We searched five databases with tailored search strings. We included studies assessing the impact of board games on elderly subjects at risk of or suffering from cognitive impairment, or subjects with cognitive impairment irrespective …of age. Studies where the effect of board games was not separated by cards or other games were excluded. A meta-analysis was performed for specific cognitive and non-cognitive outcomes. Results: Board games improved mental function, as measured by Montreal Cognitive Assessment (p = 0.003) and Mini-Mental State Examination (p = 0.02). Ska and Go improved Trail Making Test –A, while Mahjong improved executive functions. There was no consistent effect across different games on Digit Span or Categorical Fluency. Chess improved quality of life measured with the WHO-QoL-OLD scale (p < 0.00001). Mahjong temporarily improved depressive symptoms. Go increased BDNF levels and left middle temporal gyrus and bilateral putamen metabolism. Conclusions: Traditional board games may slow global cognitive decline and improve the quality of life in elderly subjects. Different games have varying impacts on specific cognitive domains, possibly mediated by functional and biological factors. Show more
Keywords: Alzheimer’s disease, cognition, dementia, primary prevention, recreational games, secondary prevention, systematic review, tertiary prevention
DOI: 10.3233/JAD-230473
Citation: Journal of Alzheimer's Disease, vol. 95, no. 3, pp. 829-845, 2023
TSPO Modulates Oligomeric Amyloid-β-Induced Monocyte Chemotaxis: Relevance for Neuroinflammation in Alzheimer’s Disease
Authors: Conti, Elisa | Grana, Denise | Angiulli, Federica | Karantzoulis, Aristotelis | Villa, Chiara | Combi, Romina | Appollonio, Ildebrando | Ferrarese, Carlo | Tremolizzo, Lucio
Article Type: Research Article
Abstract: Background: Neuroinflammation is one of the cardinal mechanisms of Alzheimer’s disease (AD). with amyloid-β (Aβ) playing a critical role by activating microglia to produce soluble inflammatory mediators, including several chemokines. Peripheral monocytes are, therefore, attracted into the central nervous system (CNS), where they change into blood-born microglia and participate in the attempt of removing toxic Aβ species. The translocator protein-18 kDa (TSPO) is a transmembrane protein overexpressed in response to neuroinflammation and known to regulate human monocyte chemotaxis. Objective: We aimed to evaluate the role of the oligomeric Aβ1-42 isoform at inducing peripheral monocyte chemotaxis, and the possible involvement of …TSPO in this process. Methods: In vitro cell lines, and ex vivo monocytes from consecutive AD patients (n = 60), and comparable cognitively intact controls (n = 30) were used. Chemotaxis analyses were carried out through both μ -slide chambers and Boyden assays, using 125 pM oligomeric Aβ1-42 as chemoattractant. TSPO agonists and antagonists were tested (Ro5-4864, Emapunil, PK11195). Results: Oligomeric Aβ directly promoted chemotaxis in all our models. Interestingly, AD monocytes displayed a stronger response (about twofold) with respect to controls. Aβ-induced chemotaxis was prevented by the TSPO antagonist PK11195; the expression of the TSPO and of the C-C chemokine receptor type 2 (CCR2) was unchanged by drug exposure. Conclusion: Oligomeric Aβ1-42 is able to recruit peripheral monocytes, and we provide initial evidence sustaining a role for TSPO in modulating this process. This data may be of value for future therapeutic interventions aimed at modulating monocytes motility toward the CNS. Show more
Keywords: Alzheimer’s disease, amyloid-β, chemotaxis, monocytes, neuroinflammation, PK11195, TSPO
DOI: 10.3233/JAD-230239
Citation: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 549-559, 2023
Adult-Onset Epilepsy in Presymptomatic Alzheimer’s Disease: A Retrospective Study
Authors: DiFrancesco, Jacopo C. | Tremolizzo, Lucio | Polonia, Valeria | Giussani, Giorgia | Bianchi, Elisa | Franchi, Carlotta | Nobili, Alessandro | Appollonio, Ildebrando | Beghi, Ettore | Ferrarese, Carlo
Article Type: Research Article
Abstract: Background: The prevalence of epilepsy with onset in adulthood increases with age, mainly due to the accumulation of brain damage. However, a significant proportion of patients experience seizures of unknown cause. Alzheimer’s disease (AD) is associated with an increased risk of seizures. Seizure activity is interpreted as a secondary event related to hyperexcitability caused by amyloid-β aggregation. Objective: Since neurodegenerative processes begin several years before clinical symptoms, epilepsy could be more frequent in the presymptomatic stages of dementia. Methods: We retrospectively reviewed the prevalence of epilepsy of unknown origin with adult onset before cognitive decline in a large cohort of …AD patients (EPS-AD) recruited based on clinical and neuropsychological data. Data of patients with epilepsy followed by AD were compared with two control groups: patients with AD without seizures (no EPS-AD) and a large reference population (RP). Results: In AD patients, the prevalence of epilepsy of unknown origin, with onset in the adulthood before cognitive decline is 17.1 times higher compared with the RP (95% CI: 10.3–28.3). In EPS-AD, seizures begin on average 4.6 years (median 2.0) before the onset of cognitive symptoms and cognitive decline starts 3.6 years earlier compared with noEPS-AD. Conclusions: Neurodegenerative processes of dementia could play a key role in the pathogenesis of epilepsy in a subgroup of individuals intended to develop cognitive decline. Adult-onset epilepsy of undefined cause could thus represent a risk factor for the ongoing neurodegenerative damage, even preceding by years the onset of clinical symptoms of dementia. Show more
Keywords: Alzheimer’s disease, disease modifying therapies, epilepsy, neurodegeneration, prevalence, seizure
DOI: 10.3233/JAD-170392
Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1267-1274, 2017
Voluptuary Habits and Risk of Frontotemporal Dementia: A Case Control Retrospective Study
Authors: Tremolizzo, Lucio | Bianchi, Elisa | Susani, Emanuela | Pupillo, Elisabetta | Messina, Paolo | Aliprandi, Angelo | Salmaggi, Andrea | Cosseddu, Maura | Pilotto, Andrea | Borroni, Barbara | Padovani, Alessandro | Bonomini, Cristina | Zanetti, Orazio | Appollonio, Ildebrando | Beghi, Ettore | Ferrarese, Carlo
Article Type: Short Communication
Abstract: Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14–0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10–0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81–0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.
Keywords: Alcohol, coffee, frontotemporal dementia, risk factor, smoking, voluptuary habits
DOI: 10.3233/JAD-170260
Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 335-340, 2017
Estimating the Inheritance of Frontotemporal Lobar Degeneration in the Italian Population
Authors: Borroni, Barbara | Grassi, Mario | Bianchi, Marta | Bruni, Amalia Cecilia | Maletta, Raffaele Giovanni | Anfossi, Maria | Pepe, Daniele | Cagnin, Annachiara | Caffarra, Paolo | Cappa, Stefano | Clerici, Francesca | Daniele, Antonio | Frisoni, Giovanni B. | Galimberti, Daniela | Parnetti, Lucilla | Perri, Roberta | Rainero, Innocenzo | Tremolizzo, Lucio | Turla, Marinella | Zanetti, Orazio | Padovani, Alessandro
Article Type: Research Article
Abstract: Frontotemporal dementia (FTD) has a strong genetic basis, with familial forms occurring in 30–50% of cases. Causative genes have been identified, with an autosomal dominant pattern of inheritance. Notwithstanding, in a number of cases with positive family history no pathogenetic mutation has been reported, and the role of genetics in sporadic cases is still unclear. In the present study, we aim to estimate the genetic contribution to FTD using concordance among parent-offspring pairs. Heritability of early-onset (EO, <65 years) and late-onset (LO, ≥65 years) FTD was estimated by examining the concordance between parents and offspring. Probands with at least one …parent whose dementia status was known were recruited from 15 Italian centers, and the presence or absence of dementia was considered in siblings. Different prevalence estimates, as available by literature data, were tested. A total of 260 probands and 1619 family members were considered in this study. We found that parent-offspring concordance in FTD was 6.25%, resulting in hereditability of 98.5% (95% confidence interval (CI): 85.0%–100.0%). Equal heritability for both sexes regardless of parental gender was reported. EO-FTD showed hereditability of 86.3% (95% CI: 77.0%–95.0%) and LO-FTD of 75.7% (95% CI: 65.0%–86.0%). Estimating the contribution of genetics in FTD may help in driving future genetic studies to identify new pathogenetic determinants. We suggest that in most of the cases FTD is a genetic-based disease, even in the elderly. Different inheritance modality might be considered in future work, beyond autosomal dominant disease. Show more
Keywords: Frontotemporal dementia, frontotemporal lobar degeneration, genetics, heritability, inheritance
DOI: 10.3233/JAD-130128
Citation: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 371-376, 2014