There are many active research projects accessing and applying shared ADNI data. Use the search above to find specific research focuses on the active ADNI investigations. This information is requested annually as a requirement for data access.
| Principal Investigator | |
| Principal Investigator's Name: | Oriol Grau |
| Institution: | BarcelonaBeta Brain Research Center |
| Department: | Alzheimer's Prevention Program |
| Country: | |
| Proposed Analysis: | Background: Growing evidence links poor sleep quality to a greater risk of dementia, and particularly to Alzheimer’s disease (AD). A bidirectional relationship between sleep disruption and AD pathology may drive the association between these two conditions: while sleep deprivation may promote amyloid βeta (Aβ) and tau accumulation through increased neuronal activity during wakefulness and impaired glymphatic clearence (Kang, 2009; Lucey, 2017), Aβ and tau accumulation may induce sleep/wake cycle disruption (Roh, 2012). This association is supported by evidence of an association between sleep quality and AD biomarkers in cognitively unimpaired adults (Carvalho, 2018; Y-E. S. Ju, 2015; Sprecher, 2017; Holth 2019). Several lines of evidence suggest that progressive accumulation of AD pathology in key regions involved in sleep-wake regulation may cause sleep disturbance to emerge early in the disease continuum, even before the appearance of the first cognitive symptoms (Ju, 2014; Mander, 2016). However, despite the natural history of AD pathology progression has been thoroughly described in seminal neuropathological studies (Braak & Braak, 1997; Braak, 2011; Thal, 2005), there is a lack of studies specifically focusing on the sequential involvement of key sleep/wake cycle regulatory center in the brain by AD pathology along the AD continuum, as well as its relationship with the presence of sleep disturbance during lifetime. The main goal of the present project is to use ADNI Neuropathology Core and clinical data to better understand which is the sequential involvement of different regions that are relevant for sleep/wake regulation in the AD natural history, as well as their association with sleep disturbance. This information will be used to generate new hypotheses and interpret eventual associations found in other studies assessing the relationship between objective sleep measures (e.g. polysomnography) and AD biomarkers in vivo. Proposed analyses: 1) To assess the presence of Alzheimer's disease (AD) pathological change (i.e. amyloid and tau deposition) in cortical and subcortical brain locations involved in sleep/wake regulation of brain donors from the ADNI cohort, irrespective of the clinical or main neuropathological diagnosis. We will focus on regions that, based on the existing literature, are known to be involved in regulation of local sleep expression such as NREM slow-wave sleep (e.g. medial prefrontal, insular and cingulate cortices), sleep spindles (e.g. thalamus) and REM sleep (e.g. cholinergic and pontine nuclei), as well as other subcortical regions involved in sleep-wake cycle regulation such as the locus coeruleus, tuberomammillary nucleus and the hypothalamus. 2) After assessing the presence of AD pathology in the aforementioned regions (if available), we will describe the sequential involvement of AD pathology using existing AD staging criteria (Braak & Braak, 1997; Thal, 2005) as a proxy of disease progression. 3) Furthermore, we will analyze associations between regional deposition of amyloid and tau (or eventually other type of pathologies) in the above-mentioned brain regions, and the presence of sleep disturbance, as determined by caregiver report on the Neuropsychiatric Inventory (NPI) or a brief questionnaire form of the NPI (NPI-Q). For this aim, we will focus on donors that were either cognitively unimpaired (with or without AD changes) or that had a clinical diagnosis of MCI / AD, with AD neuropathological confirmation. References: 1. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18(4), 351–357. https://doi.org/10.1016/S0197-4580(97)00056-0 2. Braak, H., Thal, D. R., Ghebremedhin, E., & del Tredici, K. (2011). Stages of the Pathologic Process in Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 70(11), 960–969. https://doi.org/10.1097/NEN.0b013e318232a379 3. Carvalho, D. Z, et al. (2018). Association of Excessive Daytime Sleepiness With Longitudinal -Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurology, 75(6), 672 -680. 4. Holth, J. K, et al. (2019). The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science, 2546(January), 5. eaav2546. 6. Ju, Y.-E. S, et al. (2015). Sleep and Alzheimer disease pathology - a bidirectional relationship. Nat Rev Neurol, 10(2), 115 -119. 7. Kang, J.-E, et al. (2009). Amyloid- Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, 326(5955), 1005 -1007. 8. Lucey, B. P, et al. (2017). Effect of sleep on overnight CSF amyloid- kinetics. Annals of Neurology. 9. Mander, B. A, et al. (2016). Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer'sDisease? Trends in Neurosciences, 39(8), 552 -566. 10. Roh, J. H, et al. (2012). Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer's Disease Pathology. Science Translational Medicine, 4(150), 150ra122. 11. Sprecher, K. E, et al. (2017). Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology,89(5), 445 -453. 12. Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002). Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology, 58(12), 1791–1800. https://doi.org/10.1212/WNL.58.12.1791 |
| Additional Investigators | |
| Investigator's Name: | Ana Fernández Arcos |
| Proposed Analysis: | Background: Growing evidence links poor sleep quality to a greater risk of dementia, and particularly to Alzheimer’s disease (AD). A bidirectional relationship between sleep disruption and AD pathology may drive the association between these two conditions: while sleep deprivation may promote amyloid βeta (Aβ) and tau accumulation through increased neuronal activity during wakefulness and impaired glymphatic clearence (Kang, 2009; Lucey, 2017), Aβ and tau accumulation may induce sleep/wake cycle disruption (Roh, 2012). This association is supported by evidence of an association between sleep quality and AD biomarkers in cognitively unimpaired adults (Carvalho, 2018; Y-E. S. Ju, 2015; Sprecher, 2017; Holth 2019). Several lines of evidence suggest that progressive accumulation of AD pathology in key regions involved in sleep-wake regulation may cause sleep disturbance to emerge early in the disease continuum, even before the appearance of the first cognitive symptoms (Ju, 2014; Mander, 2016). However, despite the natural history of AD pathology progression has been thoroughly described in seminal neuropathological studies (Braak & Braak, 1997; Braak, 2011; Thal, 2005), there is a lack of studies specifically focusing on the sequential involvement of key sleep/wake cycle regulatory center in the brain by AD pathology along the AD continuum, as well as its relationship with the presence of sleep disturbance during lifetime. The main goal of the present project is to use ADNI Neuropathology Core and clinical data to better understand which is the sequential involvement of different regions that are relevant for sleep/wake regulation in the AD natural history, as well as their association with sleep disturbance. This information will be used to generate new hypotheses and interpret eventual associations found in other studies assessing the relationship between objective sleep measures (e.g. polysomnography) and AD biomarkers in vivo. Proposed analyses: 1) To assess the presence of Alzheimer's disease (AD) pathological change (i.e. amyloid and tau deposition) in cortical and subcortical brain locations involved in sleep/wake regulation of brain donors from the ADNI cohort, irrespective of the clinical or main neuropathological diagnosis. We will focus on regions that, based on the existing literature, are known to be involved in regulation of local sleep expression such as NREM slow-wave sleep (e.g. medial prefrontal, insular and cingulate cortices), sleep spindles (e.g. thalamus) and REM sleep (e.g. cholinergic and pontine nuclei), as well as other subcortical regions involved in sleep-wake cycle regulation such as the locus coeruleus, tuberomammillary nucleus and the hypothalamus. 2) After assessing the presence of AD pathology in the aforementioned regions (if available), we will describe the sequential involvement of AD pathology using existing AD staging criteria (Braak & Braak, 1997; Thal, 2005) as a proxy of disease progression. 3) Furthermore, we will analyze associations between regional deposition of amyloid and tau (or eventually other type of pathologies) in the above-mentioned brain regions, and the presence of sleep disturbance, as determined by caregiver report on the Neuropsychiatric Inventory (NPI) or a brief questionnaire form of the NPI (NPI-Q). For this aim, we will focus on donors that were either cognitively unimpaired (with or without AD changes) or that had a clinical diagnosis of MCI / AD, with AD neuropathological confirmation. References: 1. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18(4), 351–357. https://doi.org/10.1016/S0197-4580(97)00056-0 2. Braak, H., Thal, D. R., Ghebremedhin, E., & del Tredici, K. (2011). Stages of the Pathologic Process in Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 70(11), 960–969. https://doi.org/10.1097/NEN.0b013e318232a379 3. Carvalho, D. Z, et al. (2018). Association of Excessive Daytime Sleepiness With Longitudinal -Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurology, 75(6), 672 -680. 4. Holth, J. K, et al. (2019). The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science, 2546(January), 5. eaav2546. 6. Ju, Y.-E. S, et al. (2015). Sleep and Alzheimer disease pathology - a bidirectional relationship. Nat Rev Neurol, 10(2), 115 -119. 7. Kang, J.-E, et al. (2009). Amyloid- Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, 326(5955), 1005 -1007. 8. Lucey, B. P, et al. (2017). Effect of sleep on overnight CSF amyloid- kinetics. Annals of Neurology. 9. Mander, B. A, et al. (2016). Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer'sDisease? Trends in Neurosciences, 39(8), 552 -566. 10. Roh, J. H, et al. (2012). Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer's Disease Pathology. Science Translational Medicine, 4(150), 150ra122. 11. Sprecher, K. E, et al. (2017). Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology,89(5), 445 -453. 12. Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002). Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology, 58(12), 1791–1800. https://doi.org/10.1212/WNL.58.12.1791 |
| Investigator's Name: | Laura Stankeviciute |
| Proposed Analysis: | Background: Growing evidence links poor sleep quality to a greater risk of dementia, and particularly to Alzheimer’s disease (AD). A bidirectional relationship between sleep disruption and AD pathology may drive the association between these two conditions: while sleep deprivation may promote amyloid βeta (Aβ) and tau accumulation through increased neuronal activity during wakefulness and impaired glymphatic clearence (Kang, 2009; Lucey, 2017), Aβ and tau accumulation may induce sleep/wake cycle disruption (Roh, 2012). This association is supported by evidence of an association between sleep quality and AD biomarkers in cognitively unimpaired adults (Carvalho, 2018; Y-E. S. Ju, 2015; Sprecher, 2017; Holth 2019). Several lines of evidence suggest that progressive accumulation of AD pathology in key regions involved in sleep-wake regulation may cause sleep disturbance to emerge early in the disease continuum, even before the appearance of the first cognitive symptoms (Ju, 2014; Mander, 2016). However, despite the natural history of AD pathology progression has been thoroughly described in seminal neuropathological studies (Braak & Braak, 1997; Braak, 2011; Thal, 2005), there is a lack of studies specifically focusing on the sequential involvement of key sleep/wake cycle regulatory center in the brain by AD pathology along the AD continuum, as well as its relationship with the presence of sleep disturbance during lifetime. The main goal of the present project is to use ADNI Neuropathology Core and clinical data to better understand which is the sequential involvement of different regions that are relevant for sleep/wake regulation in the AD natural history, as well as their association with sleep disturbance. This information will be used to generate new hypotheses and interpret eventual associations found in other studies assessing the relationship between objective sleep measures (e.g. polysomnography) and AD biomarkers in vivo. Proposed analyses: 1) To assess the presence of Alzheimer's disease (AD) pathological change (i.e. amyloid and tau deposition) in cortical and subcortical brain locations involved in sleep/wake regulation of brain donors from the ADNI cohort, irrespective of the clinical or main neuropathological diagnosis. We will focus on regions that, based on the existing literature, are known to be involved in regulation of local sleep expression such as NREM slow-wave sleep (e.g. medial prefrontal, insular and cingulate cortices), sleep spindles (e.g. thalamus) and REM sleep (e.g. cholinergic and pontine nuclei), as well as other subcortical regions involved in sleep-wake cycle regulation such as the locus coeruleus, tuberomammillary nucleus and the hypothalamus. 2) After assessing the presence of AD pathology in the aforementioned regions (if available), we will describe the sequential involvement of AD pathology using existing AD staging criteria (Braak & Braak, 1997; Thal, 2005) as a proxy of disease progression. 3) Furthermore, we will analyze associations between regional deposition of amyloid and tau (or eventually other type of pathologies) in the above-mentioned brain regions, and the presence of sleep disturbance, as determined by caregiver report on the Neuropsychiatric Inventory (NPI) or a brief questionnaire form of the NPI (NPI-Q). For this aim, we will focus on donors that were either cognitively unimpaired (with or without AD changes) or that had a clinical diagnosis of MCI / AD, with AD neuropathological confirmation. References: 1. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18(4), 351–357. https://doi.org/10.1016/S0197-4580(97)00056-0 2. Braak, H., Thal, D. R., Ghebremedhin, E., & del Tredici, K. (2011). Stages of the Pathologic Process in Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 70(11), 960–969. https://doi.org/10.1097/NEN.0b013e318232a379 3. Carvalho, D. Z, et al. (2018). Association of Excessive Daytime Sleepiness With Longitudinal -Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurology, 75(6), 672 -680. 4. Holth, J. K, et al. (2019). The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science, 2546(January), 5. eaav2546. 6. Ju, Y.-E. S, et al. (2015). Sleep and Alzheimer disease pathology - a bidirectional relationship. Nat Rev Neurol, 10(2), 115 -119. 7. Kang, J.-E, et al. (2009). Amyloid- Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, 326(5955), 1005 -1007. 8. Lucey, B. P, et al. (2017). Effect of sleep on overnight CSF amyloid- kinetics. Annals of Neurology. 9. Mander, B. A, et al. (2016). Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer'sDisease? Trends in Neurosciences, 39(8), 552 -566. 10. Roh, J. H, et al. (2012). Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer's Disease Pathology. Science Translational Medicine, 4(150), 150ra122. 11. Sprecher, K. E, et al. (2017). Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology,89(5), 445 -453. 12. Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002). Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology, 58(12), 1791–1800. https://doi.org/10.1212/WNL.58.12.1791 |
| Investigator's Name: | Núria Tort-Colet |
| Proposed Analysis: | Background: Growing evidence links poor sleep quality to a greater risk of dementia, and particularly to Alzheimer’s disease (AD). A bidirectional relationship between sleep disruption and AD pathology may drive the association between these two conditions: while sleep deprivation may promote amyloid βeta (Aβ) and tau accumulation through increased neuronal activity during wakefulness and impaired glymphatic clearence (Kang, 2009; Lucey, 2017), Aβ and tau accumulation may induce sleep/wake cycle disruption (Roh, 2012). This association is supported by evidence of an association between sleep quality and AD biomarkers in cognitively unimpaired adults (Carvalho, 2018; Y-E. S. Ju, 2015; Sprecher, 2017; Holth 2019). Several lines of evidence suggest that progressive accumulation of AD pathology in key regions involved in sleep-wake regulation may cause sleep disturbance to emerge early in the disease continuum, even before the appearance of the first cognitive symptoms (Ju, 2014; Mander, 2016). However, despite the natural history of AD pathology progression has been thoroughly described in seminal neuropathological studies (Braak & Braak, 1997; Braak, 2011; Thal, 2005), there is a lack of studies specifically focusing on the sequential involvement of key sleep/wake cycle regulatory center in the brain by AD pathology along the AD continuum, as well as its relationship with the presence of sleep disturbance during lifetime. The main goal of the present project is to use ADNI Neuropathology Core and clinical data to better understand which is the sequential involvement of different regions that are relevant for sleep/wake regulation in the AD natural history, as well as their association with sleep disturbance. This information will be used to generate new hypotheses and interpret eventual associations found in other studies assessing the relationship between objective sleep measures (e.g. polysomnography) and AD biomarkers in vivo. Proposed analyses: 1) To assess the presence of Alzheimer's disease (AD) pathological change (i.e. amyloid and tau deposition) in cortical and subcortical brain locations involved in sleep/wake regulation of brain donors from the ADNI cohort, irrespective of the clinical or main neuropathological diagnosis. We will focus on regions that, based on the existing literature, are known to be involved in regulation of local sleep expression such as NREM slow-wave sleep (e.g. medial prefrontal, insular and cingulate cortices), sleep spindles (e.g. thalamus) and REM sleep (e.g. cholinergic and pontine nuclei), as well as other subcortical regions involved in sleep-wake cycle regulation such as the locus coeruleus, tuberomammillary nucleus and the hypothalamus. 2) After assessing the presence of AD pathology in the aforementioned regions (if available), we will describe the sequential involvement of AD pathology using existing AD staging criteria (Braak & Braak, 1997; Thal, 2005) as a proxy of disease progression. 3) Furthermore, we will analyze associations between regional deposition of amyloid and tau (or eventually other type of pathologies) in the above-mentioned brain regions, and the presence of sleep disturbance, as determined by caregiver report on the Neuropsychiatric Inventory (NPI) or a brief questionnaire form of the NPI (NPI-Q). For this aim, we will focus on donors that were either cognitively unimpaired (with or without AD changes) or that had a clinical diagnosis of MCI / AD, with AD neuropathological confirmation. References: 1. Braak, H., & Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging, 18(4), 351–357. https://doi.org/10.1016/S0197-4580(97)00056-0 2. Braak, H., Thal, D. R., Ghebremedhin, E., & del Tredici, K. (2011). Stages of the Pathologic Process in Alzheimer Disease. Journal of Neuropathology and Experimental Neurology, 70(11), 960–969. https://doi.org/10.1097/NEN.0b013e318232a379 3. Carvalho, D. Z, et al. (2018). Association of Excessive Daytime Sleepiness With Longitudinal -Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurology, 75(6), 672 -680. 4. Holth, J. K, et al. (2019). The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science, 2546(January), 5. eaav2546. 6. Ju, Y.-E. S, et al. (2015). Sleep and Alzheimer disease pathology - a bidirectional relationship. Nat Rev Neurol, 10(2), 115 -119. 7. Kang, J.-E, et al. (2009). Amyloid- Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science, 326(5955), 1005 -1007. 8. Lucey, B. P, et al. (2017). Effect of sleep on overnight CSF amyloid- kinetics. Annals of Neurology. 9. Mander, B. A, et al. (2016). Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer'sDisease? Trends in Neurosciences, 39(8), 552 -566. 10. Roh, J. H, et al. (2012). Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of -Amyloid in Mice with Alzheimer's Disease Pathology. Science Translational Medicine, 4(150), 150ra122. 11. Sprecher, K. E, et al. (2017). Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology,89(5), 445 -453. 12. Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002). Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology, 58(12), 1791–1800. https://doi.org/10.1212/WNL.58.12.1791 |
