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1. Vascular Function Is Improved After an Environmental Enrichment Program

Author

Bruno, Rosa Maria, Stea, Francesco, Sicari, Rosa, Ghiadoni, Lorenzo, Taddei, Stefano, Ungar, Andrea, Bonuccelli, Ubaldo, Tognoni, Gloria, Cintoli, Simona, Del Turco, Serena, Sbrana, Silverio, Gargani, Luna, D'Angelo, Gennaro, Pratali, Lorenza, Berardi, Nicoletta, Maffei, Lamberto, Picano Eugenio, on behalf of Train the Brain Consortium. Full list of consortium members: Maffei L, Picano E, Andreassi MG, Angelucci A, Baldacci F, Baroncelli L, Begenisic T, Bellinvia PF, Berardi N, Biagi L, Bonaccorsi J, Bonanni E, Bonuccelli U, Borghini A, Braschi C, Broccardi M, Bruno RM, Caleo M, Carlesi C, Carnicelli L, Cartoni G, Cecchetti L, Cenni MC, Ceravolo R, Chico L, Cintoli S, Cioni G, Costa M, D’Angelo G, D’Ascanio P, De Nes M, Del Turco S, Di Coscio E, Di Galante M, di Lascio N, Faita F, Falorni I, Faraguna U, Fenu A, Fortunato L, Franco R, Gargani L, Gargiulo R, Ghiadoni L, Giorgi FS, Iannarella R, Iofrida C, Kusmic C, Limongi F, Maestri M, Maffei M, Maggi S, Mainardi M, Mammana L, Marabotti A, Mariotti V, Melissari E, Mercuri A, Molinaro S, Narducci R, Navarra T, Noale M, Pagni C, Palumbo S, Pasquariello R, Pellegrini S, Pietrini P, Pizzorusso T, Poli A, Pratali L, Retico A, Ricciardi E, Rota G, Sale A, Sbrana S, Scabia G, Scali M, Scelfo D, Sicari R, Siciliano G, Stea F, Taddei S, Tognoni G, Tonacci A, Tosetti M, Turchi S, Volpi L, Bruno, Rosa Maria, Stea, Francesco, Sicari, Rosa, Ghiadoni, Lorenzo, Taddei, Stefano, Ungar, Andrea, Bonuccelli, Ubaldo, Tognoni, Gloria, Cintoli, Simona, Del Turco, Serena, Sbrana, Silverio, Gargani, Luna, D'Angelo, Gennaro, Pratali, Lorenza, Berardi, Nicoletta, Maffei, Lamberto, Picano, Eugenio, on behalf of Train the Brain Consortium., Full list of consortium members: Maffei L, Picano, E, Andreassi, Mg, Angelucci, A, Baldacci, F, Baroncelli, L, Begenisic, T, Bellinvia, Pf, Berardi, N, Biagi, L, Bonaccorsi, J, Bonanni, E, Bonuccelli, U, Borghini, A, Braschi, C, Broccardi, M, Bruno, Rm, Caleo, M, Carlesi, C, Carnicelli, L, Cartoni, G, Cecchetti, L, Cenni, Mc, Ceravolo, R, Chico, L, Cintoli, S, Cioni, G, Costa, M, D’Angelo, G, D’Ascanio, P, De Nes, M, Del Turco, S, Di Coscio, E, Di Galante, M, di Lascio, N, Faita, F, Falorni, I, Faraguna, U, Fenu, A, Fortunato, L, Franco, R, Gargani, L, Gargiulo, R, Ghiadoni, L, Giorgi, F, Iannarella, R, Iofrida, C, Kusmic, C, Limongi, F, Maestri, M, Maffei, M, Maggi, S, Mainardi, M, Mammana, L, Marabotti, A, Mariotti, V, Melissari, E, Mercuri, A, Molinaro, S, Narducci, R, Navarra, T, Noale, M, Pagni, C, Palumbo, S, Pasquariello, R, Pellegrini, S, Pietrini, P, Pizzorusso, T, Poli, A, Pratali, L, Retico, A, Ricciardi, E, Rota, G, Sale, A, Sbrana, S, Scabia, G, Scali, M, Scelfo, D, Sicari, R, Siciliano, G, Stea, F, Taddei, S, Tognoni, G, Tonacci, A, Tosetti, M, Turchi, S, and Volpi, L

Subjects
Male, control groups, medicine.medical_specialty, Brachial Artery, Pulse Wave Analysis, 030204 cardiovascular system & hematology, 03 medical and health sciences, endothelial progenitor cell, 0302 clinical medicine, cognitive dysfunction, Internal medicine, medicine.artery, Internal Medicine, medicine, human, Brachial artery, Cognitive decline, humans, Pulse wave velocity, Aged, endothelial progenitor cells, Aged, 80 and over, Environmental enrichment, business.industry, control group, Area under the curve, Neuropsychology, Brain, vascular stiffness, Cognition, Middle Aged, medicine.disease, Exercise Therapy, Vasodilation, Cross-Sectional Studies, Cardiovascular Diseases, Cardiology, Female, Endothelium, Vascular, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

Environmental enrichment may slow cognitive decay possibly acting through an improvement in vascular function. Aim of the study was to assess the effects of a 7-month cognitive, social, and physical training program on cognitive and vascular function in patients with mild cognitive impairment. In a single-center, randomized, parallel-group study, 113 patients (age, 65–89 years) were randomized to multidomain training (n=55) or usual care (n=58). All participants underwent neuropsychological tests and vascular evaluation, including brachial artery flow-mediated dilation, carotid–femoral pulse wave velocity, carotid distensibility, and assessment of circulating hematopoietic CD34+ and endothelial progenitor cells. At study entry, an age-matched control group (n=45) was also studied. Compared with controls, patients had at study entry a reduced flow-mediated dilation (2.97±2.14% versus 3.73±2.06%; P =0.03) and hyperemic stimulus (shear rate area under the curve, 19.1±15.7 versus 25.7±15.1×10 −3 ; P =0.009); only the latter remained significant after adjustment for confounders ( P =0.03). Training improved Alzheimer disease assessment scale cognitive (training, 14.0±4.8 to 13.1±5.5; nontraining, 12.1±3.9 to 13.2±4.8; P for interaction visit×training=0.02), flow-mediated dilation (2.82±2.19% to 3.40±1.81%, 3.05±2.08% to 2.24±1.59%; P =0.006; P =0.023 after adjustment for diameter and shear rate area under the curve), and circulating hematopoietic CD34 + cells and prevented the decline in carotid distensibility (18.4±5.3 to 20.0±6.6, 23.9±11.0 to 19.5±7.1 Pa −1 ; P =0.005). The only clinical predictor of improvement of cognitive function after training was established hypertension. There was no correlation between changes in measures of cognitive and vascular function. In conclusion, a multidomain training program slows cognitive decline, especially in hypertensive individuals. This effect is accompanied by improved systemic endothelial function, mobilization of progenitor CD34 + cells, and preserved carotid distensibility. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01725178.

Published
2018
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2. Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects

Author

Cecchetti L., Lettieri G., Handjaras G., Leo A., Ricciardi E., Pietrini P., Pellegrini S., Andreassi M. G., Angelucci A., Baldacci F., Baroncelli L., Begenisic T., Bellinvia P. F., Biagi L., Bonaccorsi J., Bonanni E., Borghini A., Braschi C., Broccardi M., Caleo M., Carlesi C., Carnicelli L., Cartoni G., Cenni M. C., Ceravolo R., Chico L., Cioni G., Costa M., D'Ascanio P., De Nes M., Di Coscio E., Di Galante M., di Lascio N., Faita F., Falorni I., Faraguna U., Fenu A., Fortunato L., Franco R., Gargiulo R., Giorgi F. S., Iannarella R., Iofrida C., Kusmic C., Limongi F., Maestri M., Maffei M., Maggi S., Mainardi M., Mammana L., Marabotti A., Mariotti V., Melissari E., Mercuri A., Molinaro S., Narducci R., Navarra T., Noale M., Pagni C., Palumbo S., Pasquariello R., Pizzorusso T., Poli A., Retico A., Rota G., Sale A., Scabia G., Scali M., Scelfo D., Siciliano G., Tonacci A., Tosetti M., Turchi S., Volpi L., Cecchetti, L., Lettieri, G., Handjaras, G., Leo, A., Ricciardi, E., Pietrini, P., Pellegrini, S., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Costa, M., D'Ascanio, P., De Nes, M., Di Coscio, E., Di Galante, M., di Lascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargiulo, R., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Maggi, S., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Molinaro, S., Narducci, R., Navarra, T., Noale, M., Pagni, C., Palumbo, S., Pasquariello, R., Pizzorusso, T., Poli, A., Retico, A., Rota, G., Sale, A., Scabia, G., Scali, M., Scelfo, D., Siciliano, G., Tonacci, A., Tosetti, M., Turchi, S., and Volpi, L.

Subjects
Vitamin, Male, medicine.medical_specialty, Article Subject, Homocysteine, Brain activity and meditation, Longitudinal Studie, Settore BIO/09 - Fisiologia, lcsh:RC321-571, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cognition, Neuroimaging, Internal medicine, medicine, Humans, Cognitive Dysfunction, Vitamin B12, Hemodynamic, Longitudinal Studies, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Anterior cingulate cortex, 030304 developmental biology, Aged, Aged, 80 and over, 0303 health sciences, business.industry, Neuropsychology, Hemodynamics, Brain, Vitamin B 12, medicine.anatomical_structure, Endocrinology, Phenotype, Neurology, chemistry, Female, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery, Human, Research Article
Abstract

Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype. Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0 05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0 0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.

Published
2019

3. Effects of combined training on neuropsychiatric symptoms and quality of life in patients with cognitive decline

Author

Cintoli, S., Radicchi, C., Noale, M., Maggi, S., Meucci, G., Tognoni, G., Bonuccelli, U., Sale, A., Berardi, N., Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Coscia, M., Costa, M., D'Angelo, G., D'Ascanio, P., Denes, M., Delturco, S., Dicoscio, E., Digalante, M., Dilascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tonacci, A., Tosetti, M., Turchi, S., Volpi, L., Cintoli, S., Radicchi, C., Noale, M., Maggi, S., Meucci, G., Tognoni, G., Bonuccelli, U., Sale, A., Berardi, N., Maffei, L., Picano, E., Andreassi, M. G., Angelucci, A., Baldacci, F., Baroncelli, L., Begenisic, T., Bellinvia, P. F., Biagi, L., Bonaccorsi, J., Bonanni, E., Borghini, A., Braschi, C., Broccardi, M., Bruno, R. M., Caleo, M., Carlesi, C., Carnicelli, L., Cartoni, G., Cecchetti, L., Cenni, M. C., Ceravolo, R., Chico, L., Cioni, G., Coscia, M., Costa, M., D'Angelo, G., D'Ascanio, P., Denes, M., Delturco, S., Dicoscio, E., Digalante, M., Dilascio, N., Faita, F., Falorni, I., Faraguna, U., Fenu, A., Fortunato, L., Franco, R., Gargani, L., Gargiulo, R., Ghiadoni, L., Giorgi, F. S., Iannarella, R., Iofrida, C., Kusmic, C., Limongi, F., Maestri, M., Maffei, M., Mainardi, M., Mammana, L., Marabotti, A., Mariotti, V., Melissari, E., Mercuri, A., Micera, S., Molinaro, S., Narducci, R., Navarra, T., Pagni, C., Palumbo, S., Pasquariello, R., Pellegrini, S., Pietrini, P., Pizzorusso, T., Poli, A., Pratali, L., Retico, A., Ricciardi, E., Rota, G., Sbrana, S., Scabia, G., Scali, M., Scelfo, D., Sicari, R., Siciliano, G., Stea, F., Taddei, S., Tonacci, A., Tosetti, M., Turchi, S., and Volpi, L.

Subjects
Quality of life, medicine.medical_specialty, Aging, education, Psychological intervention, Neuropsychiatric symptom, Disease, Neuropsychological Tests, Settore BIO/09 - Fisiologia, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Medicine, Dementia, Humans, Mild cognitive impairment, Neuropsychiatric symptoms, Non-pharmacological interventions, Physical and cognitive training, In patient, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive decline, Aged, business.industry, Non-pharmacological intervention, Cognition, medicine.disease, Cognitive training, humanities, Physical therapy, Neuropsychological Test, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Human
Abstract

Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline. Background and aims: Cognitive impairments associated with aging and dementia are major sources of neuropsychiatric symptoms (NPs) and deterioration in quality of life (QoL). Preventive measures to both reduce disease and improve QoL in those affected are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, NPs and QoL outcomes are too commonly overlooked in intervention trials. The purpose of this study was to test the effects of physical and cognitive training on NPs and QoL in MCI. Methods: Baseline data from an MCI court (N = 93, mean age 74.9 ± 4.7) enrolled in the Train the Brain (TtB) study were collected. Subjects were randomized in two groups: a group participated to a cognitive and physical training program, while the other sticked to usual standard care. Both groups underwent a follow-up re-evaluation after 7 months from baseline. NPs were assessed using the Neuropsychiatric Inventory (NPI) and QoL was assessed using Quality of Life-Alzheimer’s Disease (QOL-AD) scale. Results: After 7 months of training, training group exhibited a significant reduction of NPs and a significant increase in QOL-AD with respect to no-training group (p = 0.0155, p = 0.0013, respectively). Our preliminary results suggest that a combined training can reduce NPs and improve QoL. Conclusions: Measuring QoL outcomes is a potentially important factor in ensuring that a person with cognitive deficits can ‘live well’ with pathology. Future data from non-pharmacological interventions, with a larger sample and a longer follow-up period, could confirm the results and the possible implications for such prevention strategies for early cognitive decline.

Published
2019

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