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 contact Dr. Kulbir Kaur at kk3347@cumc.columbia.edu.

 

To view all 10 columns, please use the horizontal scroll situated at the bottom of the table.

Key Members/ InstitutionInstitutionTheoretical 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, EiderBarcelonabeta Brain Research CenterReserve, Resilience, Maintenance, ResistanceEnvironmental (lifestyle), geneticsbiological, psychosocial, psychologicalCognitive status, cognitive declineEducation, occupation, cognitive activity, social activity, physical activity, vascular health, psychoaffective factors Observational-epidemiological and and longitudinalNeuropsych, 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 BarcelonaReserve, Resilience, MaintenanceEnviromental, geneticBiological, psychological, psychosocialCognitive status, cognitive stability & declineEducation, 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, MarselNorthwestern UniversityReserve, Resilience, Maintenance, Neuroprotection, SuperAgingEnvironmental, Genetic, ExGBiological, Psychological, PsychosocialCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIEducation, occupation, social, leisure, genetic, personality, brain volume, brain pathology, etc.Longitudinal
Experimental
Brain series
Neuropsych, CSF and Imaging Biomarkers, AutopsyOn 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, AnjeJohns Hopkins University School of MedicineReserve, Resilience, MaintenanceEnvironmental, Genetic, ExGBiological, Psychological, PsychosocialCognitive status, Cognitive decline, Incidence MCIClassical CR proxy measures (education, NART, WAIS-vocab, leisure activities, occupation), residual approach lessObservational-Epidemiologic, Longitudinal, Brain SeriesNeuropsych,
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, CorinneJohns HopkinsReserve, ResilienceEnvironmental, Genetic, E X GPsychosocialCognitive decline, Incidence of MCIClassical CR measuresObservational-Epidemiologic, LongitudinalNeuropsych, 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 ResendeUniversidade Federal de Minas Gerais (UFMG), Belo Horizonte, BrazilReserve, ResilienceEnvironmentalBiological PsychosocialCognitive status, Cognitive declineEducation, occupation, socioeconomic statusObservational-Epidemiologic, LongitudinalNeuropsych,
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, NikolaosNational and Kapodistrian University of AthensReserve, MaintenanceEnvironmentalBiologicalCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIClassical CR measuresObservational-Epidemiologic, LongitudinalNeuropsych
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, AnitaVU University Medical CenterReserve, ResilienceEnvironmental, GeneticBiologicalCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIResidual approaches (imaging vs cognition), education, physical/cognitive activity, premorbid IQObservational-Epidemiologic, LongitudinalNeuropsych
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, HenneAmsterdam UMCReserve, Resilience Maintenance, NeuroprotectionGeneticBiologicalCognitive statusgenetics, proteomics, neuropathology, all omics, with outcome measures cognitive functioning, corrected by eduction occupation etc.Observational-Epidemiologic, Longitudinal, Brain series, Cohort study of cognitively healthy centenariansNeuropsych, Autopsy studies, blood samples/ feces/ PET/MRIUsing 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 MunichReserveEnvironmental, FMRIBiological, FunctionalCognitive status, Cognitive decline, Clinical worseningMultimodal imaging; Biomarkers; Protective environmental factorsObservational, longitudinal, Functional MRINeuropsych, Neuroimaging, BiomarkersQuantifying 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, RenataPontifical Catholic University of Rio Grande do Sul - BrazilReserveEnvironmentalPsychologicalCognitive status, Cognitive decline, Incidence of dementia, Incidence of MCIclassical (education, occupation, frequency of reading and writing habits)LongitudinalNeuropsychdata not published yet
Chetelat, GaëlUniversité Normandie, Inserm,Université de Caen-Normandie, Inserm UMR-S U1237, GIP Cyceron, Caen, FranceReserve, Resilience, Maintenance, NeuroprotectionEnvironmental, Genetic, E X GBiological, Psychological, PsychosocialCognitive status, Cognitive decline, Neuroimaging biomarkersClassical CR measures (education, occupation, social, leisure); othersObservational-Epidemiologic, Longitudinal, RCTNeuropsych, 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, DharmaAlzheimer's Research and Prevention FoundationReserve, Resilience, Maintenance, Neuroprotection, AllImprovement in clinical outcomes including SCD, MCI. less depression, anxiety and better sleep and mood, biomarkers, scans, telomere measurement, others Biological, Psychological, ClinicalCognitive status, Cognitive decline, Incidence of dementia, Incidence of MCI, Reversal of SCD and MCI may lead to decreased incidence of dementiaBuilding higher levels of CR true yoga meditation and spiritual fitnessLongitudinal, Experimental, RCT, Clinical studies RCTNeuropsych, Imaging, blood biomarkers, clinical outcomes, neuropsychlogical tests, Hamilton Depression scale, Well-being scaleswww.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 HospitalMusic, ArtMusic, ArtPsychosocialCognitive status, Cognitive declineN/ALongitudinal, ExperimentalNeuropsych, CSF and imaging biomarkers,clinical outcomes, neuropsychlogical tests, Hamilton Depression scale, Well-being scalesFound repeated exposure to autobiographically salient music improved memory and functional connectivity in patients with AD/MCI
Rajji,TarekUniversity of Toronto and Centre for Addiction and Mental Health (CAMH)Reserve, ResilienceEnvironmental, Genetic, E X GBiologicalCognitive status, Cognitive decline, Incidence of dementia;Incidence of MCIEducation, occupationLongitudinal, Experimental, Brain series, RCTNeuropsych, CSF and imaging biomarkers, NeurophysiologyKumar et al; JAMA Psychiatry, 2017 Goodman et al. Frontiers Aging Neuroscience, 2018
Wirth, Miranka Charité - Universitätsmedizin BerlinReserve, Resilience, NeuroprotectionEnvironmental, E X GBiological, PsychologicalCognitive status, Cognitive declineeducation, occupation, lifelong cognitive activity, functional connectivityObservational-Epidemiologic, RCTNeuropsych, 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, EmmelineAlbert Einstein College of MedicineReserve, MaintenanceEnvironmentalBiological, Psychological,
Psychosocial
Cognitive Status, Cognitive decline,
Incidence of dementia; Incidence of MCI
Education, leisure activities, fMRI, PGSObservational-Epidemologic
Longitudinal
RCT
Neuropsych, CSF and imaging biomarkershttps://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, MarcioUniversidad Católica San Pablo, Arequipa, PerúReserveEnvironmentalPsychological, psychosocialCognitive decline
education, bilingualism, reading levelObservational-Epidemologic

Neuropsych, EEG biomarkerssubjects 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
AIBLUniversity of MelbourneResilience, SuperAgingCognitive Status, Cognitive decline, Neurodegeneration, structure-cognition relationships
SuperAging classification criteria (based on neuropsychological performance)Longitudinal
Neuropsych, CSF and imaging biomarkersSuperAger 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 ScarmeasColumbia UniversityReserve, MaintenanceEnvironmentalBiological, Psychological, PsychosocialCognitive Status, Cognitive decline,
Incidence of dementia; Incidence of MCI; Moderation pathology
Classic CR measures, residua; approaches, brain networksObservational-Epidemologic
Longitudinal
Experimental
Neuropsych, CSF and imaging biomarkers; Functional imagingCR 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 BellevilleUniversité de MontréalReserve, Resilience, NeuroprotectionEnvironmentalBiological, PsychologicalCognitive Status, Cognitive declineClassic CR measures, Moderation; fun ctional activiation; interventionsObservational-Epidemiologic
Longitudinal
Experimental
Brain series
RCT
Neuropsych, CSF and imaging biomarkersCognitive 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 MortimerUniversity of South FloridaReserve, ResilienceEnvironmental, Genetic, EXTBiological Cognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCIreaction time, education, IQ, brain sizeObservational-Epidemologic
Longitudinal
Neuropsych, CSF and imaging biomarkers, Autopsy studiesMain 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 LivingResilience, NeuroprotectionEnvironmental, ActivityBiological, PsychosocialCognitive Status, Cognitive decline, ADL, Depression
Classical CRObservational-Epidemiologic, Longitudinal
NeuropsychIn process; measuring initial data. Pre-intervention
Clouston, SeanStony Brook UniversityReserve, NeuroprotectionEnvironmentalBiological, PsychologicalCognitive decline, Incidence of MCIEducation, occupation, SESObservational-Epidemiologic
Longitudinal
Brain series

Neuropsych, CSF and imaging biomarkersCognitive 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, OziomaUW MadisonReserve, Resilience, Maintenance, NeuroprotectionEnvironmental, Genetic, EXGBiological, Psychological, PsychosocialCognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCIEducation, occupation, fitness, exercise, cognitive activities, physical activities, cognitive activities, social interaction, vascular healthObservational-Epidemologic,
Longitudinal, Brain series
Neuropsych, CSF and imaging biomarkersCardiorespiratory 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, JosephUniv. Minn. Medical School, Duluth campusSyndemic: Synergism of Biol + Soc DeterminantsEnvironmental, Genetic, Multiple Cultural Factors, Toxic StressBiological, Psychological, Psychosocial, Cultural FactorsCognitive Status, Cognitive decline, Incidence of dementia, Incidence of MCI
social determinants, APO-E4 genotype, DiabetesObservational-Epidemiologic, Community-based participatory research
CSF and imaging biomarkers, interview elicitation of perceptions of cause, course, treatmentAmer 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, MichaelUniversity of SydneyReserve Environmental, EXGBiologicalCognitive decline, Incidence of dementiaLifetime of Experiences Questionnaire (LEQ), education, occupational complexity, leisure activitiesObservational-Epidemiologic, Longitudinal, Experimental, Brain SeriesNeuropsych, Autopsy studies, sMRI1. 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 InvestigatorsMayo ClinicReserve, Resilience, ResistanceEnvironmental, EXGBiologicalCognitive decline
Education/occupation, Leisure and Physical Activities, Sleep, Vascular Health, StressObservational-Epidemologic, Longitudinal

CSF and imaging biomarkersOur 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, MiquelHospital Clinic of BarcelonaReserve, Resilience, NeuroprotectionEnvironmentalBiological, PsychologicalCognitive Status, Cognitive declineClassical CR proxy measures (education, WAIS-vocab, leisure activities, occupation)LongitudinalNeuropsychCognitive 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, AndersUmeå University, SwedenMaintenanceE x GPsychologicalCognitive statusNot used much, but residualLongitudinal
Experimental
Brain series
Neuropsy, MRI, PET biomarkersNyberg et al (2012) TiCS; Nyberg & Pudas (2019) Ann Rev Psychol.; Degerman et al (2016) Neurobiol Aging
Walhovd KB, Fjell AMCenter 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 groupWe 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 measuresEducation, family income, genetics (PGS), functional activations, Birth at weight, HC volume, WM microstructureLongitudinal, Experimental (cross, long), Training-induced interventionsNeuropsych, CSF and Imaging Biomarkers, MRI (fMRI, sMRI, DTI), Training paradigmsWM 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, RichardMRC Cognition & Brain Sciences Unit, Cambridge, UKReserve, Resilience, Maintenance, Neuroprotection, SuperAgingEnvironmental, Genetic, ExGBiological, Psychological, PsychosocialCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIEducation, occupation, social, leisure, genetic, personality, brain volume, brain pathologyObservational (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, RogierMRC Cognition & Brain Sciences Unit, Cambridge, UKReserve, Resilience, MaintenanceEnvironmental, Genetic, ExGBiological, Psychological, PsychosocialCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIClassical CR proxy measures (education, NART, WAIS, processing speed, leisure activities, occupation), mental health, cardiovascular healthresidual approaches Observational-Epidemiologic, Longitudinal, Brain SeriesNeuropsych, 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, LorraineDept of Psychology, University of CambridgeReserve, Resilience, Maintenance, Neuroprotectionenvironmental, Genetic, ExGBiological, Psychological, PsychosocialCognitive status, Cognitive decline, genetics, occupation, lifestyle factors, with outcome measures cognitive functioning, corrected by eduction occupation etc. brin measures - structural and functionalObservational-Epidemiologic, Longitudinal, Brain series, Cohort study of cognitively healthy centenariansNeuropsych, Autopsy studies, blood samples/ feces/ PET/ MRI
Rowe, JamesDept Clinical Neurosciences, Cambridge University Reserve, Resilience, NeuroprotectionEnvironmental, GeneticBiological, PsychologicalCognitive Status, Cognitive declineClassic CR measures, Moderation; fun ctional activiation; interventionsObservational-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, StefanUniversity of Bern; Department of Old Age Psychiatry and PsychotherapyReserve, Maintenance, InterventionsEnvironmentalBiological, Psychological, PsychosocialCognitive status, Cognitive declineClassical CR measures, imaging measures (e.g., volume, activity)Experimental, Longitudinal, RCTNeuropsych, Imaging, blood samples, NIBShttps://www.ncbi.nlm.nih.gov/pubmed/?term=kloppel%2C+stefan+compensation
Peter, JessicaUniversity of Bern; Department of Old Age Psychiatry and PsychotherapyReserve, Resilience, InterventionsEnvironmentalBiological, Psychological, PsychosocialCognitive status, Cognitive declineClassical CR measures, imaging measures (e.g., volume, activity)Experimental, Longitudinal, RCTNeuropsych, Imaging, blood samples, NIBSThe 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, MarcoCognitive NeuroLab, Faculty of Health SciencesReserve, ResilienceEnvironmental (bilingualism)PsychologicalCognitive status, Cognitive declineEducation, occupation, social, leisure, as covariates of the bilingualism effectExperimental
(cross-sectional)
Neuropsychology and experimental cognitive tasksResults 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, CésarJaume I University, Castellón de la Plana (Spain)Reserve, NeuroprotectionEnvironmental (bilingualism)Biological, PsychologicalCognitive status, Cognitive decline, Education as covariate of the bilingualism effectCross-sectional and longitudinalNeuropsych, Imaging Biomarkers
Staff, RogerNHS-Grampian University of AberdeenReserve, Resilience, Maintenance, NeuroprotectionEnvironmental, Genetic Biological, Psychological, PsychosocialCognitive Status, Cognitive decline, incident dementia, dealthEarly life IQ, education, personality,SES, imaging, Social activityObservational, logitudinal, imagingNeuropsych, blood and Imaging Biomarkers, SES1) 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, EmilianoBerenson-Allen Center for NonInvaiseve Brain Stmulation, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS-158, Boston, MA,USAReserve, Resilience, NeuroprotectionEnvironmental, Genetic, ExG Biological, PsychologicalCognitive status, Cognitive decline, Incidence of dementia, Incidence MCIClassic 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 StudyNeuropsychological 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 TechniquesMeasures 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, PabloFundación CITA Alzheimer, Donostia-San Sebastian (Spain)Reserve, Resilience, MaintenanceEnvironmental, ExG(APOE) Biological, Psychological, PsychosocialCognitive status, Cognitive decline, Incidence MCIClassical CR proxy measures (education,, WAIS-vocab, leisure activities, occupation, bilingualism)Observational-Epidemiologic, LongitudinalNeuropsych,
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, StefanieDZNE MagdeburgReserve, Resilience, Maintenance, Neuroprotection, SuperAging, Plasticitiy, neural resourcesEnvironmental, Genetic, VascularizationBiological, PsychologicalCognitive status, Cognitive declineClassical 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, XianghongHuntington Medical Research InstitutesReserve, Resilience, Brain resolution?Environmental, Genetic, EXGBiological, Psychological, Psychosocial, and SpiritualCognitive status, Cognitive decline, Incidence of dementia and Incidence of MCI
Brain alpha power during taskingObservational-EpidemiologicCSF and imaging biomarkers, functional EEGArakaki et al., Plos ONE, 2019
Wang, ZiqiChengdu Fifth People HospitalMaintenance, NeuroprotectionEXGBiological, Psychological and PsychosocialCognitive decline, Incidence of dementia
Education, occupation, social, leisure, wife/husband educatin, residual approachesObservational-Epidemiologic, Longitudinal, RCTNeuropysch, CSF and imaging biomarkers1. 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, JúliaInstitute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilReserve
Maintenance
Neuroprotection
Other - Write In (Required): Motor Biomarkers
EnvironmentalBiological
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, AndrewKeck School of Medicine, University of Southern CaliforniaReserve
Resilience
Maintenance
Neuroprotection
EnvironmentalBiological
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, MargaretMcMaster UniversityMaintenance
Neuroprotection
Environmental
Genetic
BiologicalCognitive declineResidual approaches, etc.
Biochemical/molecular markers Neurotrophins, proneurotrophins and related molecules
Longitudinal
Experimental
Animal models
Other - Write In (Required): Cellular models
Autopsy studies1. 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, RalphMurdoch UniversityReserve
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, SudhaAdjunct Professor of Neurology, Boston University School of Medicine
Senior Investigator, the Framingham Heart StudyGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases
ResilienceEnvironmental
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, HuqueUniversity of New South WalesResilienceEnvironmental
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, SuvarnaNational Institute of Mental Health and Neurosciences Bangalore, IndiaReserve
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, AlvaroHinda 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 HealthEnviromental, geneticBiological, psychological, psychosocialCognitive status, cognitive stability versus decline, neurophysiologic substrate to enable such clinical outcomes are criticalEducation, 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 paradigmsObservational, longitudional, experimental (imaging, EEG, TMS, tCS, cognitive), RCTsNeuropsych, 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.

 

 

*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 TreatmentAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (in press).