Reserve and Resilience Investigators*
The table below contains the answers provided by 53 research groups during a survey study undertaken by the Reserve, Resilience and Protective Factors Professional Interest Area (PIA) of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment. Besides group (or PI) identification in the first column, responses reflect each group’s answers regarding the main theoretical backgrounds, designs, methodologies and study outcomes employed in their research. Answers to the last open field question reflect the top findings considered by each group within the area.
Should you wish to add your group to this list, please write to: af2409@cumc.columbia.edu.
To view all 10 columns, please use the horizontal scroll situated at the bottom of the table.
| Key Members/ Institution | Institution | Theoretical model/concept framework that best defines the group's research work | Specific aspects of cognitive reserve | Mechanisms of Reserve | Clinical outcomes of cognitive reserve | Key measures | Methods employed | Specific techniques | Top 3-5 findings and relevant references; link to website/pubmed |
|---|---|---|---|---|---|---|---|---|---|
| • Reserve • Resilience • Maintenance • Neuro-protection • Other | Determinants of cognitive reserve: • Environment • Genetic • E X G • Other | • Biological • Psychological • Psychosocial • Other | • Cognitive status • Cognitive decline • Incidence of dementia • Incidence MCI | • Classical CR measures (education, occupation, social, leisure) • Residual approaches etc. | Study designs: • Observational- epidemiologic • Longitudinal • Experimental • Brain series • RCT • Animal models If not, please specify | • Neuropsych • CSF and imaging biomarkers • Autopsy studies • Other | |||
| Arenaza-Urquijo, Eider | Barcelonabeta Brain Research Center | Reserve, Resilience, Maintenance, Resistance | Environmental (lifestyle), genetics | biological, psychosocial, psychological | Cognitive status, cognitive decline | Education, occupation, cognitive activity, social activity, physical activity, vascular health, psychoaffective factors | Observational-epidemiological and and longitudinal | Neuropsych, CSF and imaging biomarkers | (1) Education as well as late-life cognitive and physical activities as are associated with brain structure and function and interact with APOE4 (Arenaza-Urquijo et al., Neuroimage, 2013; Arenaza-Urquijo et al., Brain Imag Behav, 2017; Arenaza-Urquijo et al., Neurology, 2015) (2) Education and stress resilience are associated with Alzheimer's disease pathologies (amyloid and tau as measured with PET imaging) (Arenaza-Urquijo et al., Neurobiol Aging, 2017, Arenaza-Urquijo et al., 2019) (3) Anterior cingulate and anterior temporal lobe FDG-PET metabolism may serve as an imaging signature of resilience at older ages (Arenaza-Urquijo et al., Brain, 2019) (4) Better mental health proxies are associated with preserved hippocampal volumes in middle-aged adults with family history of AD (Arenaza-Urquijo et al., Neurology, in press). (5) Comprehensive reviews/Research frameworks to study resilience and reserve (Bartrés-Faz & Arenaza-Urquijo, Brain Topography, 2011, Arenaza-Urquijo et al., Frontiers Aging Neurosci, 2015, Arenaza-Urquijo& Vemuri, Neurology, 2018) |
| Bartrés-Faz, David | Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona | Reserve, Resilience, Maintenance | Enviromental, genetic | Biological, psychological, psychosocial | Cognitive status, cognitive stability & decline | Education, composite (ocupational, social, physical). Psychological constructs (i.e. purpose in life) | Observational, longitudional, imaging, experimental, | Neuropsych, MRI, non-invasive brain stimulatin (TMS, tDCS). | In a series of fMRI studies including language and memory tasks, we observed dissociations between healthy subjects vs MCI or AD during cognitive demands supporting the concepts of neural efficiency and neural compensation stated in the CR theory (Bartrés-Faz et al. Biol Psychol, 2009; Solé-Padullés et al. Neurobiol Aging 2009; Bosch et al. Cortex, 2010; reviewed in Bartrés-Faz & Arenaza-Urquijo. Brain Topography, 2011). We have observed that elders with high CR estimates (using education as proxy) show funcional reorganizations to brain stimulation (TMS) more similar to younger individuals and these predict better cognitive status at longer term (Abellaneda-Pérez et al. Neuroimage 2019). -We found that highly educated elders exhibited greater cortical tichkness in anterior cingulate, medial prefrontal and orbital cortices and that these areas are characterized by a relative upregulation of family genes involved in synaptic transmission and immune adaptative processes (Bartrés-Faz et al. J Neurosci 2019). |
| Rogalski, Emily; Geula, Changiz; Mesulam, Marsel | Northwestern University | Reserve, Resilience, Maintenance, Neuroprotection, SuperAging | Environmental, Genetic, ExG | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Education, occupation, social, leisure, genetic, personality, brain volume, brain pathology, etc. | Longitudinal Experimental Brain series | Neuropsych, CSF and Imaging Biomarkers, Autopsy | On average, memory capacity is significantly higher in populations of 50–60 year olds than in populations of 80 year olds. We define SuperAgers as individuals 80 or older whose episodic memory capacity is at least as good as that of cognitively average individuals in their 50s and 60s. SuperAgers therefore have memory capacity that is superior for age. We enrolled a dedicated and unique cohort of SuperAgers committed to longitudinal assessment and brain donation at death. We identified biologic, psychosocial, and genetic features of the SuperAgers, including maintenance of cortical integrity (especially in the anterior cingulate), an abundance of anterior cingulate Von Economo neurons and sparse cortical Alzheimer pathology compared to their cognitively average peers. By identifying neurobiologic features that contribute to superior memory performance in old age, outcomes from this project aim to isolate factors that promote successful cognitive aging and perhaps also prevent age-related brain diseases such as AD. 1. Rogalski E, Gefen T, Mao Q, Connelly M, Weintraub S, Geula C, Bigio EH, Mesulam MM. Cognitive trajectories and spectrum of neuropathology in SuperAgers: The first 10 cases. Hippocampus. 2018. PMC6050141 2. Rogalski EJ, Gefen T, Shi J, Samimi M, Bigio E, Weintraub S, Geula C, Mesulam MM. Youthful memory capacity in old brains: anatomic and genetic clues from the Northwestern SuperAging Project. J Cogn Neurosci. 2013; 25: 29-36;PMID: 23198888; PMC3541673 3. Cook AH, Sridhar J, Ohm D, Rademaker A, Mesulam MM, Weintraub S, Rogalski E. Rates of Cortical Atrophy in Adults 80 Years and Older With Superior vs Average Episodic Memory. JAMA. 2017;317:1373-1375. PMC5847263 |
| Soldan, Anje | Johns Hopkins University School of Medicine | Reserve, Resilience, Maintenance | Environmental, Genetic, ExG | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Incidence MCI | Classical CR proxy measures (education, NART, WAIS-vocab, leisure activities, occupation), residual approach less | Observational-Epidemiologic, Longitudinal, Brain Series | Neuropsych, CSF and Imaging Biomarkers | We've mostly looked at interactions between proxy measures of CR and AD biomarkers in relationship to risk of progression form normal to MCI or cognitive change (Soldan et al., 2013, 2015, 2017; Pettigrew, et al., 2017). I've also done a bit of experimental work looking at neural correlates of CR using EEG (Speer & Soldan, 2015). Soldan, A., Pettigrew, C., Li, S., Wang, M., Moghekar, A., Selnes, O., Albert, M., O'Brien, R., & the BIOCARD Research Team (2013). Relationship of cognitive reserve and CSF biomarkers to emergence of clinical symptoms in preclinical Alzheimer's Disease. Neurobiology of Aging, 34(12), 2827-2834. Spear, M., & Soldan, A., (2015). Cognitive reserve modulates ERPs associated with verbal working memory in young and older adults. Neurobiology of Aging, 36(3):1424-1434. Soldan, A., Pettigrew, C., Lu, Y., Wang, M.C., Selnes, O., Albert, M., Brown, T., Ratnanather, J.T., Younes, L., Miller, M.I., & the BIOCARD Research Team. (2015). Relationship of medial temporal lobe atrophy, APOE genotype, and cognitive reserve in preclinical Alzheimer's disease. Human Brain Mapping, 36(7):2826-41. Pettigrew, C., Soldan, A., Zhu, Y., Wang, M.C., Brown, T., Miller, M., Albert, M.; BIOCARD Research Team. (2017). Cognitive reserve and cortical thickness in preclinical Alzheimer's disease. Brain Imaging and Behavior, 11(2), 357-367. Soldan, A., Pettigrew, C., Cai, Q., Wang, J., Wang, M.C., Moghekar, A., Miller, M., & Albert, M. (2017). Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease. Neurobiology of Aging, 60, 164-172. |
| Pettigrew, Corinne | Johns Hopkins | Reserve, Resilience | Environmental, Genetic, E X G | Psychosocial | Cognitive decline, Incidence of MCI | Classical CR measures | Observational-Epidemiologic, Longitudinal | Neuropsych, CSF and imaging biomarkers | - Protective effects of CR on risk of progression to MCI are independent of APOE-4 carrier statues, but stronger in APOE-2 carriers vs. non-carriers (Pettigrew et al., 2013, Cognitive Neuroscience) - Protective effects of CR on risk of progression to MCI are stronger at low (vs. high) levels of CSF tau and p-tau, but are independent of CSF amyloid (Soldan et al., 2013, NBA) - Higher engagement in lifestyle activities is associated with a reduced rate of prior cognitive decline among individuals who progress from normal cognition to MCI, but not among individuals who remain normal (Pettigrew et al., in press, ADAD) |
| Paulo Caramelli, Leonardo Cruz de Souza, Elisa de Paula França Resende | Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil | Reserve, Resilience | Environmental | Biological Psychosocial | Cognitive status, Cognitive decline | Education, occupation, socioeconomic status | Observational-Epidemiologic, Longitudinal | Neuropsych, CSF and Imaging Biomarkers | - In population-based epidemiological studies, prevalence of dementia was significantly higher in illiterate elderly in comparison to literate individuals (Herrera E et al.; Alzheimer Dis Assoc Disord; 2002; Nitrini R et al.; Int Psychogeriatrics; 2009). '- Low educational level, including illiteracy, significantly influences cognitive performance, even outside the verbal domain, e.g., limb praxis (Nitrini R et al.; Cogn Behav Neurol; 2005; Rodrigues Cavalcante K and Caramelli P; J Int Neuropsychol Soc; 2009). '- Integrity of specific white matter fasciculi seems to play a role in episodic memory performance in the low-educated elderly (Resende EPF et al.; Arq Neuropsiquiatr; 2017). '- In a DTI study, low-literate elderly subjects had significantly higher fractional anisotropy values in the right superior longitudinal fasciculus than illiterate elderly (Resende EPF et al.; Cogn Behav Neurol; in press). |
| Scarmeas, Nikolaos | National and Kapodistrian University of Athens | Reserve, Maintenance | Environmental | Biological | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Classical CR measures | Observational-Epidemiologic, Longitudinal | Neuropsych CSF and Imaging Biomarkers | Population-based epidemiological cohort [HELIAD]; prospective data just coming in Cohort of middle aged / elderly cognitively normal [not even MCI] with cognitive concerns or family history of dementia with detailed phenotypic and biomarker characterization is being developed. |
| Ossenkoppele, Rik; van Loenhoud, Anita | VU University Medical Center | Reserve, Resilience | Environmental, Genetic | Biological | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Residual approaches (imaging vs cognition), education, physical/cognitive activity, premorbid IQ | Observational-Epidemiologic, Longitudinal | Neuropsych CSF and Imaging Biomarkers | 1. Increased glucose metabolism as a potential compensatory mechanisms against amyloid-beta deposition (van Loenhoud et al. [2019] Neurology https://pubmed.ncbi.nlm.nih.gov/31266904/) 2. Meta-analysis of RCT's: Physical activity has a beneficial effect on cognition in patients with dementia (Groot et al. [2016] Ageing Research Reviews: https://www.ncbi.nlm.nih.gov/pubmed/26607411) 3. Development of a novel neuroimaging (residual) approach to capture CR (van Loenhoud et al. [2017] Human Brain Mapping: https://www.ncbi.nlm.nih.gov/pubmed/28631336) 4. Differential effects of BR and CR on cognition in AD (Groot et al. [2018] Neurology: https://www.ncbi.nlm.nih.gov/pubmed/29237798) 5. A critical appraisal of ICV as a proxy of brain reserve (van Loenhoud et al. [2018] Alzheimer's Research & Therapy: https://www.ncbi.nlm.nih.gov/pubmed/30205838) |
| Holstege, Henne | Amsterdam UMC | Reserve, Resilience Maintenance, Neuroprotection | Genetic | Biological | Cognitive status | genetics, proteomics, neuropathology, all omics, with outcome measures cognitive functioning, corrected by eduction occupation etc. | Observational-Epidemiologic, Longitudinal, Brain series, Cohort study of cognitively healthy centenarians | Neuropsych, Autopsy studies, blood samples/ feces/ PET/MRI | Using our cohort of cognitively healthy centenarians (100-plus Study): we aim to learn how a brain can remain healthy for 100 years. We study several levels of cellular regulation, both in blood and in brain. https://www.biorxiv.org/content/early/2018/04/06/295287 https://www.nature.com/articles/s41431-018-0273-5 https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-018-0558-5 https://www.biorxiv.org/content/early/2018/07/13/366328 |
| Ewers, Michael; Franzmeier, Nicolai | Institute for Stroke and Dementia Research, University Hospital LMU Munich | Reserve | Environmental, FMRI | Biological, Functional | Cognitive status, Cognitive decline, Clinical worsening | Multimodal imaging; Biomarkers; Protective environmental factors | Observational, longitudinal, Functional MRI | Neuropsych, Neuroimaging, Biomarkers | Quantifying reserve by interaction analysis of pathology vs environmental protective factors (Ewers et al. Neurology 2013). Graph theoretical analysis of resting-state fMRI hub connectivity in fronto-parietal network as a substrate of reserve in ageing and Alzheimer's disease (Franzmeier et al. Brain 2018; Neurology 2017, Frontiers Aging Neurosci 2017), hub connectivity probed during task and association with network efficiency (Franzmeier et al. Alz Res Therapy 2018; J Alzheimer Dis 2017;). Compensatory enhancement of memory network connectivity (Zhang et al Neurobiol Aging 2016). fMRI biomarker of reserve (Franzmeier et al. Brain Imaging & Behav 2017) |
| Kochhann, Renata and Fonseca, Rochele Paz | Hospital Moinhos de Vento and Pontifical Catholic University of Rio Grande do Sul - Brazil | Reserve | Environmental | Psychological | Cognitive status, Cognitive decline, Incidence of dementia, Incidence of MCI | classical (education, occupation, frequency of reading and writing habits) | Longitudinal | Neuropsych | data not published yet |
| Chetelat, Gaël | Université Normandie, Inserm,Université de Caen-Normandie, Inserm UMR-S U1237, GIP Cyceron, Caen, France | Reserve, Resilience, Maintenance, Neuroprotection | Environmental, Genetic, E X G | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Neuroimaging biomarkers | Classical CR measures (education, occupation, social, leisure); others | Observational-Epidemiologic, Longitudinal, RCT | Neuropsych, CSF and imaging biomarkers | - Brain mechanisms of cognitive resilience in amyloid-positive individuals (Chételat et al., Brain, 2010) and in ApoE4 carriers (Arenaza-Urquijo et al., Neurology, 2015) - Links between proxies of cognitive reserve and multimodal neuroimaging (MRI, FDG-PET, connectivity/resting-state fMRI) (Bastin et al., Neuroimage. 2012; Arenaza-Urquijo et al., Neuroimage. 2013) - Multimodal neuroimaging evidences of a neuroprotection – compensation continuum across the AD spectrum (Arenaza-Urquijo et al., Neurobiol Aging. 2017) - Regional-specific effects related to CR proxies (Arenaza-Urquijo et al., Brain Imaging Behav. 2017) - Meditation to strengthen reserve in the ageing population (Chételat G et al., Alzheimers Res Ther. 2018; Chételat G et al., Sci Rep. 2017) |
| Singh Khalsa, Dharma | Alzheimer's Research and Prevention Foundation | Reserve, Resilience, Maintenance, Neuroprotection, All | Improvement in clinical outcomes including SCD, MCI. less depression, anxiety and better sleep and mood, biomarkers, scans, telomere measurement, others | Biological, Psychological, Clinical | Cognitive status, Cognitive decline, Incidence of dementia, Incidence of MCI, Reversal of SCD and MCI may lead to decreased incidence of dementia | Building higher levels of CR true yoga meditation and spiritual fitness | Longitudinal, Experimental, RCT, Clinical studies RCT | Neuropsych, Imaging, blood biomarkers, clinical outcomes, neuropsychlogical tests, Hamilton Depression scale, Well-being scales | www.alzheimersprevention.org/research 1. Review article of our work published in JAD Khalsa D, Stress, Meditation and Alzheimer's Disease Prevention: Where The Evidence Stands. (2015) J Alzheimer's Dis 48 1-12 doi: 10.3233/JAD-142766 2. Reversal of MCI and increased neuro-connectivity 2A. Changes in Neural Connectivity and Memory Following a Yoga Intervention for Older Adults: A Pilot Study. Eyre, Harris A. et al, Journal of Alzheimer's Disease, vol. 52, no. 2, pp. 673-684, 2016 DOI: 10.3233/JAD-150653 2B. Neurochemical and Neuroanatomical Plasticity Following Memory Training and Yoga Interventions in Older Adults with Mild Cognitive Impairment. Hongyu Yang et al, Frontiers in Aging Neuroscience. http://dx.doi.org/10.3389/fnagi.2016.00277 2C. A Randomized Controlled Trial of Kundalini Yoga in Mild Cognitive Impairment. Harris A. Eyre et al, International Psychogeriatrics DOI: 10.1017/S1041610216002155 3. Reversal of SCD and positive measurements of multiple biomarkers. 3A. Innes K et al (2018) Effects of Meditation and Music Listening on Blood Biomarkers of cellular aging and Alzheimer's disease in Adults with Subjective Cognitive Decline: J Alzheimer's Disease ( in press). 3B. Innes K et al (2017) Meditation and Music improve cognition in adults with subjective cognitive decline. J Alzheimer's Dis 56 (3), 899-916. DOI: 10.3233/JAD-160867 3C. Innes K et al, Effects of meditation vs Music Listening on perceived Stress, Mood, Sleep, and QOL in Adults with Early Memory Loss: J Alzheimer's Dis 52, 1277-1298. DOI: 10.3233/JAD-151106 4. Chanting Meditation Increases Cerebral Blood Flow. 4A. Cerebral Blood Flow Changes During Chanting Meditation Khalsa DS et al, Nucl Med Commun. 2009 Dec;30(12):956-61. doi: 10.1097/MNM.0b013e32832fa26c. 5. Long term meditation enhances cognitive reserve. 5A. Cerebral Blood Flow Differences Between Long-Term Meditators and Non-Meditators Newberg AB et al, Conscious Cogn. 2010 Dec;19(4):899-905. doi: 10.1016/j.concog.2010.05.003 |
| Fischer, Corinne | St. Michaels Hospital | Music, Art | Music, Art | Psychosocial | Cognitive status, Cognitive decline | N/A | Longitudinal, Experimental | Neuropsych, CSF and imaging biomarkers,clinical outcomes, neuropsychlogical tests, Hamilton Depression scale, Well-being scales | Found repeated exposure to autobiographically salient music improved memory and functional connectivity in patients with AD/MCI |
| Rajji,Tarek | University of Toronto and Centre for Addiction and Mental Health (CAMH) | Reserve, Resilience | Environmental, Genetic, E X G | Biological | Cognitive status, Cognitive decline, Incidence of dementia;Incidence of MCI | Education, occupation | Longitudinal, Experimental, Brain series, RCT | Neuropsych, CSF and imaging biomarkers, Neurophysiology | Kumar et al; JAMA Psychiatry, 2017 Goodman et al. Frontiers Aging Neuroscience, 2018 |
| Wirth, Miranka | Charité - Universitätsmedizin Berlin | Reserve, Resilience, Neuroprotection | Environmental, E X G | Biological, Psychological | Cognitive status, Cognitive decline | education, occupation, lifelong cognitive activity, functional connectivity | Observational-Epidemiologic, RCT | Neuropsych, CSF and imaging biomarkers | - Functional connectivity is a neural substrate of cognitive reserve in the setting of cerebrovascular pathology (Benson et al.; Alzheimers Res Ther; 2018) - Lifelong cognitive activity may reduce brain pathology in older age and thereby promote healthy cognition(Wirth et al.; Neurobiology of Aging; 2014; Wirth et al.; Journal of Neuroscience; 2014) ) |
| Verghese, Joe; Holtzer, Roee; Blumen, Helena; Ayers, Emmeline | Albert Einstein College of Medicine | Reserve, Maintenance | Environmental | Biological, Psychological, Psychosocial | Cognitive Status, Cognitive decline, Incidence of dementia; Incidence of MCI | Education, leisure activities, fMRI, PGS | Observational-Epidemologic Longitudinal RCT | Neuropsych, CSF and imaging biomarkers | https://www.ncbi.nlm.nih.gov/pubmed/19652139 Cognitive Reserve and Postoperative Delirium in Older Adults. Tow A, Holtzer R, Wang C, Sharan A, Kim SJ, Gladstein A, Blum Y, Verghese J. J Am Geriatr Soc. 2016 Jun;64(6):1341-6. doi: 10.1111/jgs.14130. Leisure activities and the risk of dementia in the elderly. Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, Ambrose AF, Sliwinski M, Buschke H. N Engl J Med. 2003 Jun 19;348(25):2508-16. Leisure activities and the risk of amnestic mild cognitive impairment in the elderly. Verghese J, LeValley A, Derby C, Kuslansky G, Katz M, Hall C, Buschke H, Lipton RB. Neurology. 2006 Mar 28;66(6):821-7. Epub 2006 Feb 8. |
| Soto, Marcio | Universidad Católica San Pablo, Arequipa, Perú | Reserve | Environmental | Psychological, psychosocial | Cognitive decline | education, bilingualism, reading level | Observational-Epidemologic | Neuropsych, EEG biomarkers | subjects with a low level of reading skills displayed lower general cognitive performance, reduced processing speed and cognitive deficits. Soto-Añari et al. (2013). Rev Neurol. 2013 Jan 16;56(2):79-85. Illiterates bilinguals had poor performance in inhibitory control task. Soto-Añari et al. (2018). AAIC 2018 |
| AIBL | University of Melbourne | Resilience, SuperAging | Cognitive Status, Cognitive decline, Neurodegeneration, structure-cognition relationships | SuperAging classification criteria (based on neuropsychological performance) | Longitudinal | Neuropsych, CSF and imaging biomarkers | SuperAger classification is associated with lower risk of progression from CN to MCI/dementia over 8 years. While SuperAgers have higher verbal memory/executive function performance than those who are cognitively normal for their age (CNFA), the rate of change in these cognitive measures is the same for both groups and SuperAgers were not resistant to the effects of elevated amyloid burden on cognitive decline compared to CNFA. Individuals without elevated amyloid burden showed reduced rates of cognitive decline (Dang et al.; Archives of Clinical Neuropsychology; 2018) | ||
| Yaakov Stern, Christian Habeck, Jason Steffener, Nikolaos Scarmeas | Columbia University | Reserve, Maintenance | Environmental | Biological, Psychological, Psychosocial | Cognitive Status, Cognitive decline, Incidence of dementia; Incidence of MCI; Moderation pathology | Classic CR measures, residua; approaches, brain networks | Observational-Epidemologic Longitudinal Experimental | Neuropsych, CSF and imaging biomarkers; Functional imaging | CR theoretical model (CR, BR) and core concepts - Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. JINS 2002;8:448-460. - Barulli D, Stern Y. Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve. Trends Cogn Sci. 2013;7(10): 502-509. • Epidemiologic – population-based and CR in the presence of neurological changes. - Stern Y, Gurland B, Tatemichi T, Tang MX, Wilder D, Mayeux R. Influence of education & occupation on the incidence of Alzheimer's disease. JAMA 1994;271:1004-1010. - Stern Y, Albert S, Tang M-X, Tsai W-Y. Rate of memory decline in AD is related to education and occupation: Cognitive reserve? Neurology 1999;53:1942-1957. - Stern Y, Alexander GE, Prohovnik I, Mayeux R. Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease. Ann Neurol 1992;32:371-375 - Scarmeas N, Levy G, Tang MX, Manly J, Stern Y. Influence of leisure activity on the incidence of Alzheimer's disease. Neurology. 2001;57:2236-42. • Neural basis of CR: unique / multiple brain mechanisms (imaging) supporting CR ((neural compensation, neural reserve) - Review: Stern Y. Cognitive Reserve. Neuropsychologia 2009;47:2015–2028. - Neural reserve/neural compensation: Stern Y, Habeck C, Moeller J, Scarmeas N, Anderson KE, Hilton HJ, et al. Brain networks associated with cognitive reserve in healthy young and old adults. CerebCortex. 2005;15:394-402. - Neural compensation and CR: Steffener J, Stern Y. Exploring the neural basis of cognitive reserve in aging. Biochim Biophys Acta. 2012;1822:467-73. - Neural efficiency and CR: Habeck C, Hilton HJ, Zarahn E, Flynn J, Moeller JR, Stern Y. Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of non-verbal memory. Neuroimage. 2003;20:1723-33. - Task invariant CR netwrk: Stern Y, Gazes Y, Razlighi Q, Steffener J, Habeck C. A task-invariant cognitive reserve network. Neuroimage 2018;176:36-45. |
| Sylvie Belleville | Université de Montréal | Reserve, Resilience, Neuroprotection | Environmental | Biological, Psychological | Cognitive Status, Cognitive decline | Classic CR measures, Moderation; fun ctional activiation; interventions | Observational-Epidemiologic Longitudinal Experimental Brain series RCT | Neuropsych, CSF and imaging biomarkers | Cognitive training can provide late-life protective effects (Belleville et al, Brain, 2011; Belleville et al, PLOS-ONE, 2014.; Moderation analyses provide evidence that functional recruitment of new brain regions provides neural substrate for reserve. |
| James Mortimer | University of South Florida | Reserve, Resilience | Environmental, Genetic, EXT | Biological | Cognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCI | reaction time, education, IQ, brain size | Observational-Epidemologic Longitudinal | Neuropsych, CSF and imaging biomarkers, Autopsy studies | Main findings over the past 15 years include elucidation of the role of brain size and eduatin in dementia showing both to be important; and factor analysis and SEM modeling of autopsy data showing that reserve as indicated by brain weight and eduation to be as or more important in comparison with the severity of Alzheimer pathology in predicting dementia. Borenstein, A.R. and Mortimer, J.A.: Alzheimer's Disease: Life Course Perspectives on Risk Reduction. New York: Elsevier Academic Press, 2016.; Mortimer, J.A., et al. Alzheimer's and Dementia, 2018.; Mortimer, J.A. et al. Alzheimer's and Dementia 2014.; Mortimer, J.A., et al. Alzheimer's and Dementia, 2012.; Mortimer, J.A..:, Future Neurology, 2009.; Mortimer, J.A. et al. Alzheimer's Dis. Assoc. disord., 2008.; Mortimer, J.A., et al. J. Clin. Exp. Neuropsychol. 2003 |
| Roche, Joan | Keystone Senior Living | Resilience, Neuroprotection | Environmental, Activity | Biological, Psychosocial | Cognitive Status, Cognitive decline, ADL, Depression | Classical CR | Observational-Epidemiologic, Longitudinal | Neuropsych | In process; measuring initial data. Pre-intervention |
| Clouston, Sean | Stony Brook University | Reserve, Neuroprotection | Environmental | Biological, Psychological | Cognitive decline, Incidence of MCI | Education, occupation, SES | Observational-Epidemiologic Longitudinal Brain series | Neuropsych, CSF and imaging biomarkers | Cognitive training can provide late-life protective effects (Belleville et al, Brain, 2011; Belleville et al, PLOS-ONE, 2014.; Moderation analyses provide evidence that functional recruitment of new brain regions provides neural substrate for reserve. |
| Okonkwo, Ozioma | UW Madison | Reserve, Resilience, Maintenance, Neuroprotection | Environmental, Genetic, EXG | Biological, Psychological, Psychosocial | Cognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCI | Education, occupation, fitness, exercise, cognitive activities, physical activities, cognitive activities, social interaction, vascular health | Observational-Epidemologic, Longitudinal, Brain series | Neuropsych, CSF and imaging biomarkers | Cardiorespiratory fitness attenuates age-associated aggregation of white matter hyperintensities in an at-risk cohort. Vesperman CJ, Pozorski V, Dougherty RJ, Law LL, Boots E, Oh JM, Gallagher CL, Carlsson CM, Rowley HA, Ma Y, Bendlin BB, Asthana S, Sager MA, Hermann BP, Johnson SC, Cook DB, Okonkwo OC. Alzheimers Res Ther. 2018 Sep 24;10(1):97. doi: 10.1186/s13195-018-0429-0.; Social support and verbal interaction are differentially associated with cognitive function in midlife and older age. Zuelsdorff ML, Koscik RL, Okonkwo OC, Peppard PE, Hermann BP, Sager MA, Johnson SC, Engelman CD. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2019 Mar;26(2):144-160. doi: 10.1080/13825585.2017.1414769. Epub 2017 Dec 15.; BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention. Boots EA, Schultz SA, Clark LR, Racine AM, Darst BF, Koscik RL, Carlsson CM, Gallagher CL, Hogan KJ, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Dubal DB, Engelman CD, Johnson SC, Okonkwo OC. Neurology. 2017 May 30;88(22):2098-2106. doi: 10.1212/WNL.0000000000003980. Epub 2017 May 3.; Chronotropic Response and Cognitive Function in a Cohort at Risk for Alzheimer's Disease. Law LL, Schultz SA, Boots EA, Einerson JA, Dougherty RJ, Oh JM, Korcarz CE, Edwards DF, Koscik RL, Dowling NM, Gallagher CL, Bendlin BB, Carlsson CM, Asthana S, Hermann BP, Sager MA, Johnson SC, Cook DB, Stein JH, Okonkwo OC. J Alzheimers Dis. 2017;56(1):351-359. doi: 10.3233/JAD-160642. |
| Henderson, Joseph | Univ. Minn. Medical School, Duluth campus | Syndemic: Synergism of Biol + Soc Determinants | Environmental, Genetic, Multiple Cultural Factors, Toxic Stress | Biological, Psychological, Psychosocial, Cultural Factors | Cognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCI | social determinants, APO-E4 genotype, Diabetes | Observational-Epidemiologic, Community-based participatory research | CSF and imaging biomarkers, interview elicitation of perceptions of cause, course, treatment | Amer Indian people may have some genetic protection from AD: Low freq of E4 among Amer. Indians with high indigenous gene loads (J. Neil Henderson, et al., Neurosci Letters, 2002).; Some Am. Indians interpret symptoms such as hallucinations as pre-death views into the afterworld. (J. Neil Henderson and John Traphagan, Alz Dis & Assoc Disorders, 2005).; Understanding dementia perceptions and progression must be analyzed in cultural and stage context. Henderson, J. Neil (2015) Cultural Construction of Dementia Progression, Behavioral Aberrations, and Situational Ethnicity: An Orthogonal Approach. Care Management Journals 16:95-105.; Toxic stress of indigenous colonial conditions may predispose to vascular dementia. Henderson, J. Neil, Carson, L. D., and King, Kama (due out in Sept. 2019) Indigenous Vascular Dementia: A Colonized Syndemic Hypothesis. In Indigeneity and Dementia, (W. Hulko, Ed.). University of British Columbia Press: Vancouver. |
| Valenzuela, Michael | University of Sydney | Reserve | Environmental, EXG | Biological | Cognitive decline, Incidence of dementia | Lifetime of Experiences Questionnaire (LEQ), education, occupational complexity, leisure activities | Observational-Epidemiologic, Longitudinal, Experimental, Brain Series | Neuropsych, Autopsy studies, sMRI | 1. Neurohistological correlates of cognitive reserve deteriminants: Valenzuela MJ, Matthews FE, Brayne C, Ince P, Halliday G, Kril JJ, Dalton MA, Richardson K, Forster G and Sachdev PS. Multiple Biological Pathways Link Cognitive Lifestyle to Protection from Dementia. Biological Psychiatry (May 2012); 71(9):783-91 Suo, C., Leon, I., Brodaty, H., Trollor, J. N., Wen, W., Sachdev, P. & Valenzuela, M. Supervisory experience at work is linked to low rate of hippocampal atrophy in late life. Neuroimage (Nov 2012); 63(3):1542-51 C Suo, N Gates, M Fiatarone Singh, N Saigal, GC Wilson, J Meiklejohn, P Sachdev, H Brodaty, W Wen, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Michael J Valenzuela. Midlife managerial experience is linked to late life hippocampal morphology and function. Brain Imaging and Behavior, (2017) 11(2), 333-345. 2. LEQ tool for assessment of environmental cognitive reserve determinants:Valenzuela M & Sachdev P. Assessment of Complex Mental Activity Across the Lifespan: Development of the Lifetime of Experiences Questionnaire. Psychological Medicine (Jul 2007); 37(7):1015-1025 Valenzuela M, Sachdev P, Chen X, Wen W, Brodaty H. Lifespan mental activity predicts diminished rate of hippocampal atrophy. PLoS ONE (Jul 2008); 3(7):e2598 M. J. Valenzuela, I. Leon, C. Suo, D. Martinez Piamba, N. Kochan, H. Brodaty and P. Sachdev. Cognitive Lifestyle in Older Persons: the Population-based Sydney Memory & Ageing Study. Journal of Alzheimer's Disease, (Jan 2013);36(1):87-97 3. sMRI correlates of environmental cognitive reserve determinants, focusing on occupational complexity: Suo, C., Leon, I., Brodaty, H., Trollor, J. N., Wen, W., Sachdev, P. & Valenzuela, M. Supervisory experience at work is linked to low rate of hippocampal atrophy in late life. Neuroimage (Nov 2012); 63(3):1542-51 C Suo, N Gates, M Fiatarone Singh, N Saigal, GC Wilson, J Meiklejohn, P Sachdev, H Brodaty, W Wen, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Michael J Valenzuela. Midlife managerial experience is linked to late life hippocampal morphology and function. Brain Imaging and Behavior, (2017) 11(2), 333-345. |
| Prashanthi Vemuri and Mayo Clinic Study of Aging Investigators | Mayo Clinic | Reserve, Resilience, Resistance | Environmental, EXG | Biological | Cognitive decline | Education/occupation, Leisure and Physical Activities, Sleep, Vascular Health, Stress | Observational-Epidemologic, Longitudinal | CSF and imaging biomarkers | Our work has been primarily focused on development of early biomarkers for detecting disease related changes and applying them to understand mechanisms through which protective factors influence aging and dementia related disease processes. Here are specific publications that are relevant to the PIA. • Cognitive Performance: Cross-sectional CSF and imaging biomarkers (Vemuri et. al. Brain 2011 and Vemuri et. al. Annals of Neurology 2012). • Longitudinal Cognitive Decline: Intellectual lifestyle and longitudinal cognitive outcomes (Vemuri et. al. JAMA Neurology 2014) and AD, CVD, Intellectual lifestyle, and longitudinal cognitive decline (Vemuri et. al. Brain 2015). • Resilience and Imaging Outcomes: APOE4, intellectual lifestyle, and longitudinal imaging trajectories (Vemuri. et. al. Neurology 2016), Amyloid and neurodegeneration outcomes (Vemuri et. al. JAMA Neurology 2017), Systemic Vascular Health (Vemuri et. al. Annals of Neurology 2017 and 2018; Fatemi et. al. Neurology 2018, and Ramanan VK et. al. JAD 2018), Sleep and Brain Health (Carvalho DZ et. al. Sleep Med 2017 and Carvalho DZ et. al. JAMA Neurology 2018), and metabolic signature for cognitive resilience in 80+ (Arenaza-Urquijo E et. al. Brain 2019). • Opinion Papers: Arenaza-Urquijo E and Vemuri P Neurology 2018 and Vemuri et. al. Alz, Res, and Therapy 2018. |
| Amoretti, Silvia; Vieta, Eduard; Bernardo, Miquel | Hospital Clinic of Barcelona | Reserve, Resilience, Neuroprotection | Environmental | Biological, Psychological | Cognitive Status, Cognitive decline | Classical CR proxy measures (education, WAIS-vocab, leisure activities, occupation) | Longitudinal | Neuropsych | Cognitive reserve predicts baseline and long-term neuropsychological outcome, negative symptoms and functioning in a first-episode psychosis sample (Amoretti et al.; European Neuropsychopharmacology; 2016) |
| Nyberg, Lars; Pudas, Sara; Wåhlin, Anders | Umeå University, Sweden | Maintenance | E x G | Psychological | Cognitive status | Not used much, but residual | Longitudinal Experimental Brain series | Neuropsy, MRI, PET biomarkers | Nyberg et al (2012) TiCS; Nyberg & Pudas (2019) Ann Rev Psychol.; Degerman et al (2016) Neurobiol Aging |
| Walhovd KB, Fjell AM | Center for Lifespan Changes in Brain and Cognition (LCBC) | Not strong relience on CNA models/frameworks but Maintenance, Reserve and Neuroplasticity have been used in our group | We do not tend to use CR in our studies. We do not outline a clear distintion between CR and BR. | Biological (HC volume, ICV,weight at birth, poligenetic scores), Years of Education, Parents income, Sleep. | We have never used a CR framework. We use cognitive status, cognitive decline, brain decline/change as outcome measures | Education, family income, genetics (PGS), functional activations, Birth at weight, HC volume, WM microstructure | Longitudinal, Experimental (cross, long), Training-induced interventions | Neuropsych, CSF and Imaging Biomarkers, MRI (fMRI, sMRI, DTI), Training paradigms | WM microstructure in the older group is predictive of Method of Loci training memory gains in aging. (de Lange et al., 2016, NoA PMID: 27565301). Maintenance of frontal brain function during encoding seems to be a primary characteristic of preservation of memory function in aging. We showed low levels of activity in frontal networks were associated with low memory performance in the older adults only. Low-performing older adults exhibited a strong longitudinal memory decline spanning 8 years back and were also characterized by lower hippocampal volumes and steeper rates of cortical atrophy. (Vidal-Piñeiro, 2018, CerCor; PMID: 30137326). Birth weight and parental education exert continued influences throughout the lifespan on brain (cortical area) and cognition (general cognitive ability). (Walhovd, 2016, PNAS, PMID: 27432992) We found that longitudinal measures of cortical atrophy were widely correlated with sleep quality (Sexton, 2014, Neurology, PMID: 25186857) |
| Henson, Richard | MRC Cognition & Brain Sciences Unit, Cambridge, UK | Reserve, Resilience, Maintenance, Neuroprotection, SuperAging | Environmental, Genetic, ExG | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Education, occupation, social, leisure, genetic, personality, brain volume, brain pathology | Observational (plans for longitudinal) | Neuropsych, Imaging Biomarkers (MRI+MEG) | Results associated with CamCAN cohort: www.cam-can.org, including: 1) Chan, D., Shafto, M., Kievit, R., Matthews, F., Spink, M., Valenzuela, M., Cam-CAN & Henson, R.N. (2018). Lifestyle activities in mid-life contribute to cognitive reserve in late-life, independent of education, occupation and late-life activities. Neurobiology of Aging, 70, 180-183. 2) de Mooij, S. M. M., Henson, R. N., Waldorp, L. J., Kievit, R. A.. (2018). Age differentiation within grey matter, white matter and between memory and white matter in an adult lifespan cohort. Journal of Neuroscience, 38, 5826-5836. 3).Morcom, A. CamCAN, Henson, R. N. (2018). Increased prefrontal activity with aging reflects nonspecific neural responses rather than compensation. Journal of Neuroscience, 1701-1717. 4) Strommer, J.M., Davis, S.W., Henson, R.N., Tyler, L.K., Cam-CAN, Campbell K.L. Physical activity predicts population-level age-related differences in frontal white matter (in press). The Journals of Gerontology: Series A. BioRxiv 5) Borgeest, G., Henson, R., Shafto, M., Samu, D., CamCAN, Kievit, R. Greater lifestyle engagement is associated with healthy cognitive ageing. BioRxiv. |
| Kievit, Rogier | MRC Cognition & Brain Sciences Unit, Cambridge, UK | Reserve, Resilience, Maintenance | Environmental, Genetic, ExG | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Classical CR proxy measures (education, NART, WAIS, processing speed, leisure activities, occupation), mental health, cardiovascular healthresidual approaches | Observational-Epidemiologic, Longitudinal, Brain Series | Neuropsych, quantitative modeling (SEM), MRI (DWI and T1) | Results associated with CamCAN cohort: www.cam-can.org, including: 1) Fuhrmann, D., Nesbitt, D., Shafto, M., Rowe, J. B., Price, D., Gadie, A., ... & Kievit R A (2019). Strong and specific associations between cardiovascular risk factors and white matter micro-and macrostructure in healthy aging. Neurobiology of aging, 74, 46-55. 2) de Mooij, S. M. M., Henson, R. N., Waldorp, L. J., Kievit, R. A.. (2018). Age differentiation within grey matter, white matter and between memory and white matter in an adult lifespan cohort. Journal of Neuroscience, 38, 5826-5836. 3).Morcom, A. CamCAN, Henson, R. N. (2018). Increased prefrontal activity with aging reflects nonspecific neural responses rather than compensation. Journal of Neuroscience, 1701-1717. 4) Strommer, J.M., Davis, S.W., Henson, R.N., Tyler, L.K., Cam-CAN, Campbell K.L. Physical activity predicts population-level age-related differences in frontal white matter (in press). The Journals of Gerontology: Series A. BioRxiv 5) Borgeest, G., Henson, R., Shafto, M., Samu, D., CamCAN, Kievit, R. Greater lifestyle engagement is associated with healthy cognitive ageing. BioRxiv. |
| Tyler, Lorraine | Dept of Psychology, University of Cambridge | Reserve, Resilience, Maintenance, Neuroprotection | environmental, Genetic, ExG | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, | genetics, occupation, lifestyle factors, with outcome measures cognitive functioning, corrected by eduction occupation etc. brin measures - structural and functional | Observational-Epidemiologic, Longitudinal, Brain series, Cohort study of cognitively healthy centenarians | Neuropsych, Autopsy studies, blood samples/ feces/ PET/ MRI | |
| Rowe, James | Dept Clinical Neurosciences, Cambridge University | Reserve, Resilience, Neuroprotection | Environmental, Genetic | Biological, Psychological | Cognitive Status, Cognitive decline | Classic CR measures, Moderation; fun ctional activiation; interventions | Observational-Epidemiologic Longitudinal Experimental | Neuropsych, imaging biomarkers (fMRI, MRI, MEG ) | https://scholar.google.com/citations?user=2_i6GTYAAAAJ&hl=en ; ftd.neurology.cam.ac.uk ; www.cam-can.org ; |
| Klöppel, Stefan | University of Bern; Department of Old Age Psychiatry and Psychotherapy | Reserve, Maintenance, Interventions | Environmental | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline | Classical CR measures, imaging measures (e.g., volume, activity) | Experimental, Longitudinal, RCT | Neuropsych, Imaging, blood samples, NIBS | https://www.ncbi.nlm.nih.gov/pubmed/?term=kloppel%2C+stefan+compensation |
| Peter, Jessica | University of Bern; Department of Old Age Psychiatry and Psychotherapy | Reserve, Resilience, Interventions | Environmental | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline | Classical CR measures, imaging measures (e.g., volume, activity) | Experimental, Longitudinal, RCT | Neuropsych, Imaging, blood samples, NIBS | The modulating effect of tDCS in MCI/ AD depends on cognitive reserve as assessed by years of education or the cognitive reserve index questionnaire. In AD, tDCS significantly improved episodic memory in those with lower CR while in patients with MCI only those with higher CR benefited significantly. The study is not published yet but will be submitted soon. |
| Calabria, Marco | Cognitive NeuroLab, Faculty of Health Sciences | Reserve, Resilience | Environmental (bilingualism) | Psychological | Cognitive status, Cognitive decline | Education, occupation, social, leisure, as covariates of the bilingualism effect | Experimental (cross-sectional) | Neuropsychology and experimental cognitive tasks | Results from the study 'Active bilingualism delays the onset of mild cognitive impairment' (Neuropsychologia, 2020) https://www.sciencedirect.com/science/article/abs/pii/S0028393220302013 Main findings: 1. Results from multiple regression analyses showed that active bilingualism (as a composite score calculated with a prinicipal componente analysis) was a significant predictor of delay in the age at onset for all the clinical measures in MCI, but not AD patients. 2. The effect of active bilingualism was independent of occupation, educational level and job attainment across the individuals' lifespan. 3. Although we did not find an effect of active bilingualism across all EC tasks, we did find an effect for conflict resolution |
| Ávila, César | Jaume I University, Castellón de la Plana (Spain) | Reserve, Neuroprotection | Environmental (bilingualism) | Biological, Psychological | Cognitive status, Cognitive decline, | Education as covariate of the bilingualism effect | Cross-sectional and longitudinal | Neuropsych, Imaging Biomarkers | |
| Staff, Roger | NHS-Grampian University of Aberdeen | Reserve, Resilience, Maintenance, Neuroprotection | Environmental, Genetic | Biological, Psychological, Psychosocial | Cognitive Status, Cognitive decline, incident dementia, dealth | Early life IQ, education, personality,SES, imaging, Social activity | Observational, logitudinal, imaging | Neuropsych, blood and Imaging Biomarkers, SES | 1) What provides cerebral reserve? June 2004Brain 127(Pt 5):1191-9 DOI: 10.1093/brain/awh144 2) The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases. November 2011Brain 134(Pt 12):3687-96. DOI: 10.1093/brain/awr259 3) Intellectual engagement and cognitive ability in later life (the "use it or lose it" conjecture): Longitudinal, prospective study. December 2018 BMJ Clinical Research 363:k4925. DOI: 10.1136/bmj.k4925 4) The influence of childhood intelligence, social class, education and social mobility on memory and memory decline in late life. August 2018 Age and Ageing 47(6). DOI: 10.1093/ageing/afy111 5) Life-course determinants of cognitive reserve (CR) in cognitive aging and dementia – a systematic literature review. July 2017Aging and Mental Health 22(8):1-12 DOI:10.1080/13607863.2017.1348471 PUBMED: https://www.ncbi.nlm.nih.gov/pubmed/?term=aberdeen+birth+cohort |
| Santarnecchi, Emiliano | Berenson-Allen Center for NonInvaiseve Brain Stmulation, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS-158, Boston, MA,USA | Reserve, Resilience, Neuroprotection | Environmental, Genetic, ExG | Biological, Psychological | Cognitive status, Cognitive decline, Incidence of dementia, Incidence MCI | Classic CR measures (education, social, leisure time activities and working occupation); IQ; Graph Theory Measures of individual functional and structural MRI and DTI data (connectomics-related estimates of resilience and reserve) | Experimental, Brain Series, Genetic, Healthy and Pathological Cohorts Study | Neuropsychological Testing, Genetic Testing, Imaging Biomarkers (MRI, fMRI, ASL), Electrophysiology Biomarker (e.g. EEG), Mathematical modeling (e.g. Network-Control Theory, Epidemiological Spreading models); NonInviasive Brain Stimulation Techniques | Measures of Brain Resilience have been investigated focusing on the association between Resilience and topological properties of brain networks, as explicated by Graph Theory estimates and neuroimaging-derived connectome analysis. In particular, we have highlighted the importance of distributed communication efficiency of brain networks as a key factor underlying brain robustness to targeted and random lesions/perturbation (Santarnecchi et al., Cortex, 2015); furthermore, we have showed how weak, long‐distance brain funcitonal connections account for the vast majority of interindiviudal differences in IQ and reserve (Santarnecchi et al., Human Brain Mapping, 2014). We have looked at psychological aspects of resilience (i.e. traits related to the ability to cope with stress) identifying resting-state fMRI networks supporting higher levels of Coping in healthy individuals (Santarnecchi et al. 2018, CABN). Most recently, we have started investigating Noninvasive Brain Stimultion techniques as a mean toward the quantification of Resilience via so-called "Perturbationo-based biomarkers", and as a possible tool to augment it (Santarnecchi & Rossi, The Spanish Journal of Psychology, 2016). Moreover, we have recently investigated the role of genetics in defining individual brain resilience levels, by looking at MRI and GWAS data of ~500 monozygotic and dizygotic twins (Menardi, in preparation). Finally, we have recently worked on a model of cognitive reserve accounting for cortical excitability changes in healthy and pathological aging (Menardi et al., Journal of Alzheimer's Disease, 2018). |
| Estanga, Ainara; Martinez-Lage, Pablo | Fundación CITA Alzheimer, Donostia-San Sebastian (Spain) | Reserve, Resilience, Maintenance | Environmental, ExG(APOE) | Biological, Psychological, Psychosocial | Cognitive status, Cognitive decline, Incidence MCI | Classical CR proxy measures (education,, WAIS-vocab, leisure activities, occupation, bilingualism) | Observational-Epidemiologic, Longitudinal | Neuropsych, CSF and Imaging Biomarkers | In a cohort of cognitively healthy middle-aged participants (Gipuzkoa Alzheimer Proyect-GAP study) we found a beneficial effect of bilingualism (early and late) compared to monolingualism on executive and visuospatial functions performance. Moreover, early bilingualism was related to a better CSF AD-biomarker profile and showed a moderation effect on the association between age and CSF AD-biomarkers. (Estanga et al., Neurobiol Aging, 2017) |
| Maass, Anne; Düzel, Emrah; Schreiber, Stefanie | DZNE Magdeburg | Reserve, Resilience, Maintenance, Neuroprotection, SuperAging, Plasticitiy, neural resources | Environmental, Genetic, Vascularization | Biological, Psychological | Cognitive status, Cognitive decline | Classical CR proxy measures, pathology measures (PET, CSF), neuroimaging structural and functional measures (connectivtiy, activation patterns) | Observational-Epidemiologic Longitudinal Intervention studies | Neuropsych, CSF and Imaging Biomarkers (inlcuding 7T MRI) | We are specifcally interested in vascular plasticity (exercise;see Maass et al., 2014; Molecular Psychiatry) and also how hippocampal vascularization patterns might serve as a protective factor against pathology or contribute to resilience in the face of pathology (see Spallazzi et al, 2019, Neuroimage Clinical). Further interest lies on differences in network function, activation as potential compensatory factor (e.g. Maass, et al, 2019, Brain). |
| Arakaki, Xianghong | Huntington Medical Research Institutes | Reserve, Resilience, Brain resolution? | Environmental, Genetic, EXG | Biological, Psychological, Psychosocial, and Spiritual | Cognitive status, Cognitive decline, Incidence of dementia and Incidence of MCI | Brain alpha power during tasking | Observational-Epidemiologic | CSF and imaging biomarkers, functional EEG | Arakaki et al., Plos ONE, 2019 |
| Wang, Ziqi | Chengdu Fifth People Hospital | Maintenance, Neuroprotection | EXG | Biological, Psychological and Psychosocial | Cognitive decline, Incidence of dementia | Education, occupation, social, leisure, wife/husband educatin, residual approaches | Observational-Epidemiologic, Longitudinal, RCT | Neuropysch, CSF and imaging biomarkers | 1. Inadequate intake of legume and animal oil associated with the prevalence of MCI. (Ziqi Wang et al.; BMC Public Health, 2010) 2. Women show better verbal memory than men in aMCI despite similar levels of brain hypometabolism. (Erin E Sundermann et al.; Neurology. 2016 Nov 1) 3. Among Aβ-positive individuals, greater CR related to attenuated clinical progression in predementia stages of AD, but accelerated cognitive decline after the onset of dementia. (Anna Catharina van Loenhoud et al.; Neurology. 2019) |
| Camaz Deslandes, Andrea; de Oliveira Silva, Felipe; Vinícius Alves Ferreira, José, Placido, Jéssica; Figueiredo, Luiz Felipe; Silveira, Heitor; Teixeira, Ivan Abdalla; Reis Fabiano Neves, Tatiana; Bem de Almeida, Creso Alberto; Silva de Almeida, Júlia | Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil | Reserve Maintenance Neuroprotection Other - Write In (Required): Motor Biomarkers | Environmental | Biological Psychosocial | Cognitive status Cognitive decline Incidence of dementia Incidence of MCI Other - Write In (Required): Assessment of symptoms of depression, anxiety and physical function | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. Physical Function | Observational-Epidemiologic Longitudinal Experimental RCT | Neuropsych Other - Write In (Required): Physical function tests | 1. Three months of multimodal training contributes to mobility and executive function in elderly individuals with mild cognitive impairment, but not in those with Alzheimer's disease: A randomized controlled trial (https://doi.org/10.1016/j.maturitas.2019.04.217); 2. Stages of mild cognitive impairment and Alzheimer’s disease can be differentiated by declines in timed up and go test: A systematic review and meta-analysis (https://doi.org/10.1016/j.archger.2019.103941; 3.Treadmill training as an augmentation treatment for Alzheimer’s disease: a pilot randomized controlled study (https://doi.org/10.1590/0004-282X20130231). 4. Spatial Navigation in the Elderly With Alzheimer's Disease: A Cross-Sectional Study (https://doi.org/10.3233/jad-180819); 5.Exercise and Mental Health: Many Reasons to Move (https://doi.org/10.1159/000223730). |
| Chen, Jiu-Chiuan (J.C.); Petkus, Andrew | Keck School of Medicine, University of Southern California | Reserve Resilience Maintenance Neuroprotection | Environmental | Biological Psychosocial | Cognitive status Cognitive decline Incidence of dementia Incidence of MCI | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. Residual approaches; MIMIC | Observational-Epidemiologic Longitudinal | Neuropsych Other - Write In (Required): brain MRI | Petkus AJ, Resnick S, Rapp SR, Espeland MA, Gatz M, Widaman K, Wang X, Younan D, Casanova R, Chui HC, Barnard RT, Gaussoin S, Goveas JS, Hayden KM, Henderson VM, Sachs BC, Saldana S, Shadyab AH, Shumaker SA, Chen JC. General and domain-specific cognitive reserve, mild cognitive impairment, and dementia risk in older women Alzheimer's & Dementia : Translational Research & Clinical Interventions 2019, 5: 118-128 |
| Fahnestock, Margaret | McMaster University | Maintenance Neuroprotection | Environmental Genetic | Biological | Cognitive decline | Residual approaches, etc. Biochemical/molecular markers Neurotrophins, proneurotrophins and related molecules | Longitudinal Experimental Animal models Other - Write In (Required): Cellular models | Autopsy studies | 1. BDNF levels correlate with cognitive decline. Peng et al, J Neurochem. 2005. 2. ProNGF and neurodegeneration in Alzheimer's disease. Fahnestock & Shekari, Frontiers Neurosci 2019. 3. Exercise + antioxidant diet increases BDNF & improves cognition. Fahnestock et al, Neurobiol Aging 2012. |
| Sohrabi, Hamid; Martins, Ralph | Murdoch University | Reserve Resilience Maintenance Neuroprotection | Environmental Genetic | Biological Psychological Psychosocial | Cognitive status Cognitive decline Incidence of dementia Incidence of MCI | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. education, occupation, social, leisure, and Residual approaches | Observational-Epidemiologic Longitudinal Experimental | Neuropsych CSF and imaging biomarkers Other - Write In (Required): Blood Biomarkers | Our research include familial, young onset dementia and sporadic late onset AD. Manuscript under preparation |
| Seshadri, Sudha | Adjunct Professor of Neurology, Boston University School of Medicine Senior Investigator, the Framingham Heart StudyGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases | Resilience | Environmental Genetic E X G | Biological Psychological Psychosocial Other - Write In (Required): Built Environment | Cognitive status Cognitive decline Incidence of dementia Incidence of MCI Other - Write In (Required): Cognitive health in oldest-old | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. Genomic, Epigenetic, Mitochondrial, MRI imaging, pathology, blood biomarkers like IGF and BDNF | Observational-Epidemiologic Longitudinal Experimental Brain series RCT | Neuropsych CSF and imaging biomarkers Autopsy studies | Population epidemiology and genetic epidemiology studies |
| Anstey, K.J.; Maccora, J.; Eramudugolla, R.; Peters, Huque | University of New South Wales | Resilience | Environmental Genetic E X G Other - Write In (Required): demographic | Biological Psychological Psychosocial | Cognitive status Cognitive decline Incidence of dementia Incidence of MCI | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. education, occupation, brain metrics, neuropsychological metrics | Observational-Epidemiologic Longitudinal Brain series | Neuropsych Other - Write In (Required): Lifecourse epidemiology | McDermott, K.L., McFall, G.P., Andrews, S.J., Anstey, K.J., & Dixon, R.A. (Nov 2016). Memory resilience to Alzheimer's genetic risk: Sex effects in predictor profiles. Journal of Gerontology: Psychological Sciences doi: 10.1093/geronb/gbw161. Anstey, K.J., & Dixon, R.A. Resilience in Mid-life and Aging, in Handbook of Psychology and Aging, 9th Edition. Editors, Willis, S. & Schaie, W. in press. Maccora, J, Peters, R, Anstey, K.J. Gender differences in superior-memory SuperAgers and associated factors in an Australian Cohort 2020 doi.org/10.1177/0733464820902943 |
| Alladi, Suvarna | National Institute of Mental Health and Neurosciences Bangalore, India | Reserve Resilience | Environmental Genetic | Biological Psychological | Cognitive status Cognitive decline | Classical CR measures (education, occupation, social, leisure). Residual approaches, etc. Education, Bilingualism, social networking, traditional occupations like craft | Observational-Epidemiologic Experimental | Neuropsych CSF and imaging biomarkers | Our research group focuses on the potentially protective role of literacy, education, bilingualism, complex traditional occupations like craft on age at onset of dementia and it's subtypes: AD, FTD, Vascular dementia and the neural mechanisms of cognitive reserve in diverse settings, especially in context of LMIC Alladi et al, Neurology 2013, Alladi et al Neurology 2018 Alladi et al Stroke 2016 Alladi et al Neuropsychologia 2017 |
| Pascual-Leone, Alvaro | Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health - Hebrew SeniorLife and Department of Neurology, Harvard Medical School, Boston MA; Guttmann Brain Health Insitut, Institut Guttmann de Neurorehabilitacion, Barcelona | Reserve, Resilience, Maintenance, Neuroprotection, Neuroplasticity, Brain Health | Enviromental, genetic | Biological, Psychological, Psychosocial | Cognitive status Cognitive stability versus decline Neurophysiologic substrate to enable such clinical outcomes are critical | Education, developmental history (lofe-long approaches), lifestyle metrics (several defined pillar including physical activity, cognitive activity, nutrition, sleep, social relations, psychological constructs); neurophysiologic metris - EEG, perturbation biomarkers with TMS, modulation with tCS; dual task paradigms | Observational, longitudional, experimental (imaging, EEG, TMS, tCS, cognitive), RCTs | Neuropsych, MRI and other imaging, EEG, non-invasive brain stimulatin (TMS, tDCS). | My scientific work combines various brain imaging and brain stimulation techniques to examine causal relations between patterns of brain activity, cognitive processes, and behavior in health and disease. An overarching goal has been the development of translational approaches to characterize and modulate brain activity to sustain brain health across the lifespan, prevent age-related disability and help patients with debilitating neuropsychiatric disorders while gaining fundamental insights into human brain function. Towards this goal I have contributed to the development of translatable perturbation-based biomarkers and the field of therapeutic brain stimulation. For a list of published work see http://www.ncbi.nlm.nih.gov/pubmed/?term=pascual-leone+a. A major focus of my work is to characterize and promote brain health across the lifespan and minimize disability in patients with neuropsychiatric disorders while gaining fundamental insights into human brain function. Translational efforts have spanned basic, animal research, human trials, and the launch of patient-centered clinical programs that includes the Brain Fit ClubTM and the Memory A2Z ProgramTM that focus on personalized interventions to minimize disability and prevent disease. I helped define and lead the Football Players Health Study at Harvard University which is dedicated to understanding the causes of the health problems that are faced by former professional American-style football players with the goal of improving their health and wellbeing. This work has led to an extension to promote deeper understanding into the effects of physical exercise on brain plasticity and function. In 2016 I brought together a team of international investigators and funding partners to establish the Barcelona Brain Health Initiative which I lead as its scientific director along with David Bartres-Faz (PI) and Jose M. Tormos. This large longitudinal cohort study aims at identifying markers of brain and cognitive health across the lifespan, and developing and testing multimodal lifestyle interventions to prevent age-related cognitive decline and minimize the risk of brain-related disability. |
| Cadar, Dorina; Almeida-Meza, Pamela | University College London, Department of Behavioral Science and Health | Reserve Resilience Maintenance Neuroprotection Successful aging | Environment (lifestyle) Genetic EXG | Biological Psychological Psychosocial | Cognitive status | Classical CR measures (education, occupation, social, leisure) Residual approaches, etc. | Observational - epidemiologic Longitudinal Experimental | Neuropsych | We constructed a Cognitive Reserve Index as a composite measure of education, occupation and leisure activities, using a standardised questionnaire. Cox proportional hazards regression models were used to estimate the hazard ratios of dementia in relation to cognitive reserve levels (low, medium and high) and its components (education, occupation and leisure activities). Our study showed a reduced risk of dementia for individuals with a higher level of cognitive reserve, represented by higher education, complex occupations and multifaceted level of leisure activities. Almeida-Meza, P., Steptoe, A., & Cadar, D. (2020). Markers of cognitive reserve and dementia incidence in the English Longitudinal Study of Ageing. The British Journal of Psychiatry, 1-9. doi:10.1192/bjp.2020.54 DOI: https://doi.org/10.1192/bjp.2020.54 Published online by Cambridge University Press: 30 March 2020 In the current study, we investigated the heterogeneity of cognitive trajectories at the end of life by assigning individuals into groups according to their cognitive trajectories prior to death. We also examined the role of childhood intelligence and education as proxies of cognitive reserve on these trajectories and group membership. Participants were drawn from the Lothian Birth Cohort of 1921 (LBC1921), a longitudinal study of individuals with a mean age of 79 years at study entry, and observed up to a maximum of five times to their early 90s. Cadar, D., Robitaille, A., Pattie, A., Deary, I. J., & Muniz-Terrera, G. (2020). The long arm of childhood intelligence on terminal decline: Evidence from the Lothian Birth Cohort 1921. Psychology and Aging. DOI: http://dx.doi.org/10.1037/pag0000477 We investigated the association between education, as a marker of cognitive reserve and change in memory in early old age using data from 10 countries of the Survey of Health, Ageing and Retirement in Europe. We modelled memory decline as a function of time in the study over an 8-year period, fitting independent latent growth models. Education was used as a marker of cognitive reserve and evaluated in association with memory performance and rate of change, while accounting for income, general health, smoking, body mass index, gender, and baseline age. We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment. Cadar, D., Robitaille, A., Clouston, S., Hofer, S. M., Piccinin, A. M., & Muniz-Terrera, G. (2017). An international evaluation of cognitive reserve and memory changes in early old age in ten European countries. Neuroepidemiology. doi: 10.1159/000452276 |
| Rory Boyle; Rachel Buckley; Gillian Coughlan; Michael Properzi; Dorene Rentz | Massachusetts General Hospital/Harvard Medical School/Brigham and Women's Hospital | Reserve, Resilience, Resistance | Environmental, Genetic, Biomarkers, Sex Differences | Biological | Cognitive status; Cognitive decline (Onset and rate of) | Residual approaches; Cognition; Multimodal imaging; Biomarkers | Observational-epidemiologic; Longitudinal; Brain series | Neuropsych; Neuroimaging; Amyloid and Tau-PET; Biomarkers | 1) Buckley et al. (2017) Neurology: Intrinsic connectivity of the default mode, frontoparietal, and salience networks moderated the relationship between amyloid burden and cognitive decline such that those with stronger connectivity in these networks had slower cognitive decline, despite elevated amyloid burden. 2) Dumitrescu et al. (2020) Brain: GWAS of clinical trial and longitudinal cohort data suggested that the genetic architecture of resilience is distinct to the genetic architecture of clinical Alzheimers disease and identified a possible resilience gene in the bile acid metabolism pathway. 3) Bettcher et al. (2019) Neurobiology of Aging: Latent variable/residual measure of cognitive reserve protected against the negative effect of brain atrophy on cognitive decline and was more rapidly depleted in individuals who display clinical deterioration. |
| Jagust, William; Harrison, Theresa; Pezzoli, Stefania | UC Berkeley | Resilience, Reserve, Resistance | Neurobiological (biomarkers), environmental, physical activity | Biological, Psychological | Cognitive status, cognitive trajectory, conversion to impairment | Classical proxies (edu, WAIS, etc), residual approaches, combination/ composite measures, lifestyle measures, health measures | Longitudinal observational studies of aging and clinical progression; lifestyle interventions | Neuropsycholo gical testing, neuroimaging biomarkers, genetics, lifestyle questionnaires , personality tests | 1) Development of a single measure of resilience using proxy-based (early-life) and residuals-based (later-life) measures that moderates the effect of AD pathology on cognitive decline in cognitively normal older adults (Dobyns et al., 2021). 2) Development of a novel definition of successful cognitive aging (SA) based on a cognitive age prediction model (Pezzoli et al., 2023). SA is characterized by greater anterior cingulate thickness and hippocampal volume, regardless of SA definition (Harrison et al., 2018; Pezzoli et al., 2023). Moreover, lower entorhinal tau deposition,but not amyloid beta is related to SA (Pezzoli et al., 2023). A combination of cortical integrity and resistance to tau may be features of SA. |
*Bartrés-Faz D, Arenaza-Urquijo E, Ewers M, Belleville S, Chételat G, Franzmeier N, Gonneaud J, González de Echevarri JM, Okonkwo O, Schultz S, Valenzuela M, Stern Y, Vemuri P. Theoretical frameworks and approaches used within the Reserve, Resilience an Protective Factors professional interest area of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (in press).