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Table 2 Characteristics of the reviewed longitudinal studies

From: Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer’s disease and cognitively unimpaired individuals

No. Author Study population (cohort) Follow-up duration AT(N) Biomarkers Biomarker method / assay NPS instrument NPS with association Significant findings
1 Binette et al. 2020 [45] 115 CU at-risk for AD
3 years A
[18F]NAV4694-PET, global SUVR
[18F]AV1451-PET, SUVR in Braak stages I, III, IV
GDS-S, AES, Geriatric anxiety scale, Stress subscale, Big5 inventory Apathy, anxiety • ↓ A associated with ↓ anxiety and apathy at baseline
• ↓ T associated with ↓ apathy at baseline
• No longitudinal association between A, T and NPS
2 Babulal et al. 2016 [54] 118 CU at baseline (9 with mood disorder)
66 CU on follow-up
(Washington University)
1 year A
N (CSF total tau)
PiB-PET, MCBP cut-off used median split
CSF Aβ42, total tau, ptau181 ELISA. Cut-off values used median split
POMS-SF, GDS-S, NPI-Q Total mood disturbance, NPI-Q score, anxiety and depressive symptoms • ↑ A longitudinally associated with ↑ total mood disturbance, anxiety, depression scores on POMS-SF, ↑ NPI-Q score and ↑ GDS-S score
• T and N predicted longitudinal changes in NPI-Q score
3 Blasko et al. 2010 [55] 331 CU
(VITA cohort)
2.5 years A Sandwich Aβ ELISA DSM-IV criteria, GDS Depression • ↑ A at baseline predicted late-onset depression
4 Direk et al. 2013 [56] 657 nondemented
(Rotterdam study)
11 years A Sandwich Aβ ELISA CES-D, HADS Depressive symptoms • ↑ A associated with ↑ depressive symptoms at baseline and subsequent incident dementia
5 Donovan et al. 2018 [57] 270 CU (HABS) 5 years A PiB-PET, DVR as continuous variable GDS Anxious-depressive symptoms • ↑ A longitudinally associated with ↑ GDS and anxiety-concentration scores
6 Gatchel et al. 2019 [58] 276 CU - 22 with mild depression
1 year A
N (HV, glucose metabolism)
PiB-PET, DVR cut-off > 1.20
GDS GDS score • ↑ A moderated the longitudinal association between ↑ depressive symptoms and ↑ cognitive decline
7 Harrington et al. 2017 [59] 359 CU (AIBL) 54 months A PiB-PET, SUVR cut-off ≥1.5 GDS-S Incident depression • ↑ A longitudinally associated with ↑ incident depression
8 Johansson et al. 2020 [60] 104 CU
53 MCI
4 years A
N (GM thickness, subcortical volumes)
[18F] flutemetamol PET, SUVR cut-off > 1.42
AES, HADS Apathy, anxiety • ↑ A longitudinally associated with ↑ apathy, ↑ anxiety over time
• ↑ N longitudinally associated with ↑ apathy over time (in CU and MCI subjects)
9 Perin et al. 2018 [61] 585 CU (AIBL) 72 months A PiB-PET, SUVR cut-off ≥1.5 GDS-S GDS-S score, apathy-anxiety symptoms • ↑ A longitudinally associated with ↑ GDS-S score and apathy-anxiety symptoms
10 Qiu et al. 2015 [62] 223 CU - 68 depressed
(NAME cohort)
6.2 years A Sandwich Aβ ELISA, Aβ + cut-off used median split of plasma Aβ40/Aβ42 ratio CES-D Nil • No association between A and depression
11 Ng et al. 2017 [63] 33 preclinical AD – A + T+
60 at-risk for AD - A + T- or A-T+
22 healthy control
2 years N (Glucose metabolism) FDG-PET NPI NPI-Q score • ↑ NPI-Q score predicted longitudinal ↓ glucose metabolism in preclinical AD
  1. ↑: higher/greater; ↓ lower/lesser, A amyloid-β; AD Alzheimer’s disease, ADNI Alzheimer’s Disease Neuroimaging Initiative, AES Apathy Evaluation Scale, AI anterior insula, AIBL Australian Imaging, Biomarker & Lifestyle Study of Ageing, amyloid-β, 40 amyloid-β 1–40; 42 amyloid-β 1–42, CES-D Center for Epidemiological Studies Depression Scale, CSF cerebrospinal fluid, CU cognitively unimpaired, DSM-IV Diagnostic and Statistical Manual of Mental Disorders-IV, DVR distribution volume ratio, ELISA enzyme linked immunosorbent assay, FDG fluorodeoxyglucose, GDS geriatric depression scale, GDS-S geriatric depression scale short form, GM grey matter, HABS Harvard Aging Brain Study, HADS Hospital Anxiety and Depression Scale, HV hippocampal volume, MCBP mean cortical binding potential, MCI mild cognitive impairment, N neurodegeneration, NAME, Nutrition, Aging and Memory in the Elderly study, NPI Neuropsychiatric Inventory, NPI-Q Neuropsychiatric Inventory Questionnaire, OR odds ratio, PCC posterior cingulate cortex, PET positron emission tomography PiB Pittsburgh Compound B, POMS-SF Profile of Mood States - Short Form, ptau181 phosphorylated tau181, SUVR standardized uptake value ratio, T tau, VITA Vienna Transdanube Aging study, vmPFC ventromedial prefrontal cortex