TABLE 2.
Systematic Literature Review of Studies Examining Aβ Biomarkers and Cortical Integrity in Cognitively Normal Older Adults
| Study | Cohort | N | Mean age (SD) | Biomarker modality | GM∼Aβ | GM∼Tau | Description of findings: |
|---|---|---|---|---|---|---|---|
| Desikan et al. PLoS One 2010 | Alzheimer's Disease Neuroimaging Initiative (ADNI) | 208 | 76.0 (4.9) | CSF | Neg | Neg | Aβ+ subjects had decreased GM compared to Aβ– subjects in F. Tau+ subjects had decreased GM compared to tau– subjects in T. |
| Glodzik et al. Neurobiol Aging 2012 | Center for Brain Health and Alzheimer's Disease Center at NYU School of Medicine | 115 | 62.6 (9.5) | CSF | Neg | Neg | Aβ+/tau+ subjects had decreased GM compared to Aβ–/tau– subjects in P, T, L, W. Tau negatively predicted GM in P, T. Tau+ subjects had decreased GM compared to tau– subjects in P, L, T. |
| Stricker et al. Brain Imaging Behav. 2012 | ADNI | 103 | 75.5 (5.21) | CSF | Null | Neg | In all subjects, tau negatively predicted F GM. |
| Fortea et al. Alzheimers Dement 2014 | ADNI | 145 | 73.4 (6.2) | CSF | Pos | Neg | In tau– subjects, Aβ positively predicted P, O, T, GM. In Aβ+ subjects, tau negatively predicted F, P, O, T GM. |
| Wang et al. Neurology 2015 | Knight Alzheimer's Disease Research Center at Washington University | 188 | 73.0 (6.0) | CSF | Null | Neg | In tau+ subjects, tau negatively predicted P, O, T, L GM. |
| Pettigrew et al. Neuroimage Clin 2017 | Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) | 207 | 56.9 (10.0) | CSF | Null | Null | |
| Maass et al. J Neurosci 2018 | Berkeley Aging Cohort Study (BACS) | 83 | 77 (6) | PET | Null | Neg | In all subjects, tau negatively predicted T GM. In Aβ+ subjects, tau was negatively related to change in T GM. In Aβ– subjects, tau was negatively related to change in T GM. |
| Montal et al. Alzheimers Dement 2018 | Hospital de Sant Pau, Barcelona, Spain; Hospital Marqués de Valdecilla, Satander, Spain; CITA Alzheimer, San Sebastian, Spain | 254 | 58.6 (7.7) | CSF | Neg, Pos | Neg | Aβ+/tau‐–subjects had increased GM compared to Aβ–/tau– subjects in P, T. Aβ+/T+ subjects had decreased GM compared to Aβ–/tau– subjects in T. |
| Batzu et al. Neurobiol Aging 2019 | ADNI | 122 | 72.3 (5.7) | CSF | Neg, Pos | Neg | Aβ+/tau– subjects had increased GM compared to Aβ–/tau– subjects in F, P, O. Aβ+/tau+ subjects had decreased GM compared to Aβ–/tau– subjects in F. |
| Luo et al. Front Neurosci 2019 | ADNI | 76 | 75.0 (5.5) | CSF | Null | Null | |
| Becker et al. Ann Neurol 2011 | Massachusetts General and Brigham and Women's Hospitals, and referring memory clinics (S.S., G.M., and D.M.) | 87 | 75.0 (8.0) | PET | Neg | N/A | In all subjects, Aβ negatively predicted F, P, T, L GM. Aβ+ subjects had decreased GM compared to Aβ– subjects in F, P, L. |
| Arenaza‐Urquijo et al. J Alzheimers Dis 2013 | Alzheimer's Disease and Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Barcelona, Spain | 33 | 70.3 (7.1) | CSF | Neg | N/A | Aβ+ subjects had decreased GM compared to Aβ– subjects in F, P, T, L. |
| Doré et al. JAMA Neurol 2013 | Australian Imaging Biomarkers and Lifestyle Study of Ageing (AIBL) | 93 | 73.9 (7.4) | PET | Neg | N/A | Aβ+ subjects had decreased GM in P, L compared to Aβ– subjects. In Aβ+ subjects, Aβ negatively predicted P, T, L GM. Aβ+ subjects had an increased rate of GM atrophy than Aβ– subjects in P, T, L. |
| Whitwell et al. Neuroimage Clin 2013 | Mayo Clinic Alzheimer's Disease Research Center and Mayo Clinic Study of Aging (MCSA) | 230 | 80* | PET | Neg, Pos | N/A | Aβ+ subjects had increased GM compared to Aβ– subjects in P; Aβ+ subjects had decreased GM compared to Aβ– subjects in F, O, P, T |
| Kljajevic et al. Neurobiol Aging 2014 | ADNI | 57 | 76.7 (5.8) | PET | Null | N/A | |
| Araque et al. Neurobiol Aging 2015 | ADNI | 40 | 75.2 (6.8) | PET | Neg | N/A | In all subjects, Aβ+ subjects had a higher rate of GM atrophy compared to Aβ– in P, O, L. |
| Doherty et al. Alzheimers Dement (Amst) 2015 | Wisconsin Registry for Alzheimer's Prevention (WRAP) | 109 | 60.7 (5.7) | PET | Neg | N/A | Aβ+ subjects had decreased GM compared to Aβ– subjects in T. |
| Kaffashian et al. Neurobiol Aging 2015 | Three‐City Dijon Study | 1187 | 72.0 (3.98) | CSF | Neg | N/A | Subjects in the highest tertile of Aβ at baseline and follow‐up had faster GM atrophy in W than those in the lowest tertile. |
| Llado‐Saz et al. Neurobiol Aging 2015 | Laboratory of Functional Neuroscience at Pablo de Olavide University | 120 | 68.9 (3.7) | CSF | Neg | N/A | Aβ+ subjects had decreased GM compared to Aβ– subjects in F, T. |
| Mattsson et al. Neurology 2015 | ADNI | 280 | 73.6(6.3) | PET | Null | N/A | |
| Susanto et al. J Alzheimers Dis 2015 | ADNI | 103 | 75.5 (5.2) | CSF | Neg | N/A | Aβ+ subjects had decreased GM compared to Aβ–subjects in P. |
| Hanseeuw et al. Alzheimers Dement 2016 | Harvard Aging Brain Study (HABS) | 250 | 73.8 (6.0) | PET | Null | N/A | |
| Hedden et al. Cereb Cortex 2016 | HABS | 186 | 73.8 (6.0) | PET | Neg | N/A | In all subjects, Aβ negatively predicted T, L GM. |
| Li et al. J Alzheimers Dis 2017 | ADNI | 251 | 75.5 (6.5) | PET | Null | N/A | |
| Sala‐Llonch et al. J Alzheimers Dis 2017 | N/A | 89 | 73.1 (6.0) | CSF | Neg | N/A | In Aβ+ subjects, Aβ negatively predicted F GM. |
| Voevodskaya et al. Neurobiol Aging 2017 | Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFinder) | 299 | 73.3 (5.0) | CSF | Null | N/A | |
| Wolk et al. Neurobiol Aging 2017 | ADNI | 86 | 74.3 (6.9) | PET | Null | N/A | |
| Knopman et al. Neurobiol Aging 2018 | MCSA | 1164 | 70.0 (10.0) | PET | Neg | N/A | In all subjects, Aβ negatively predicted O, T GM. |
| Ten Kate et al. Alzheimers Res Ther 2018 | European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF‐AD MBD) | 337 | 66.5 (7.2) | PET | Neg | N/A | Aβ+ subjects had decreased GM compared to Aβ– subjects in O, T. |
| Haller et al. Front Neurosci 2019 | University Hospitals of Geneva | 133 | 76.8 (4.0) | PET | Null | N/A | |
| Rabin et al. JAMA Neurol 2019 | HABS | 182 | 73.4 (6.2) | PET | Neg | N/A | In all subjects, Aβ negatively predicted W GM. |
| Rahayel et al. Eur J Nucl Med Mol Imaging 2019 | Centre de recherche de l'Institut universitaire de gériatrie de Montréal (CRIUGM) | 103 | 73.4 (6.2) | PET | Neg, Pos | N/A | In all subjects, Aβ negatively predicted F and positively predicted F, T GM. |
Abbreviations: Aβ, amyloid beta; F, frontal lobe; GM, gray matter; L, limbic lobe (cingulate gyrus, parahippocampal gyrus, dentate gyrus); Neg, negative association between pathology biomarker and cortical measure; Null, no significant association between pathology biomarker and cortical measure; O, occipital lobe; P, parietal lobe; Pos, positive association between pathology biomarker and cortical measure; SD, standard deviation; T, temporal lobe; W, whole cortex.
Notes: Studies testing cross‐sectional associations between Aβ and cortical integrity (thickness or volume) in cognitively healthy older adults. Citation, cohort, sample size, mean age, and pathology biomarker modality are listed in addition to a brief summary of results. The locations of cortical areas with significant results are noted by the lobe of the brain for brevity. Studies including Aβ and tau biomarkers are listed in chronological order followed by studies with only an Aβ biomarker in chronological order.
*This study reported a median age.