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Table 2 Potential protective factors for cognitive impairment in the oldest-old

From: Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study

Domain Potential protective factor Study Agea Sample size (N) Outcome variable Result
Cognitive reserve High level of education H85 Gothenburg study [18] 85.7 (±0.05) No dementia: 794
Dementia: 271
Dementia Protective
The 90+ Study [4] 94 (90–106) No dementia: 536
Dementia: 375
Dementia Protective
Vantaa 85+ Study [17] 88.4 (85.0–104.0) No incident dementia: 239
Incident dementia: 100
Incident dementia Protective
High cognitive activity The 90+ Study [16] 93 (90–103) No incident dementia: 319
Incident dementia: 268
Incident dementia Equivocal
Vascular comorbidity Low total/LDL or high HDL cholesterol level Leiden 85-plus Study [20] 85 (85) No dementia: 488
Dementia: 73
Cognition
Dementia
Equivocal
Newcastle 85+ Study [19] 85 (85) No dementia: 767
Dementia: 78
Cognition
Cognitive decline
Equivocal
NonaSantfeliu study [21] 94.3 (±2.6) 62, dementia status unknown Cognition No effect
Octabaix study [22] 85 (85) 321, dementia status unknown Cognition No effect
PLAD [15] 93.6 (90–108) No cognitive impairment: 300
Cognitive impairment: 409
Cognition No effect
Vantaa 85+ Study [17] 88.4 (85.0–104.0) No incident dementia: 239
Incident dementia: 100
Incident dementia No effect
Absence of hypertension Leiden 85-plus Study [23] 85 (85) 572, dementia status unknown Cognition
Cognitive decline
Risk
Newcastle 85+ Study [19] 85 (85) No dementia: 767
Dementia: 78
Cognition
Cognitive decline
Equivocal
PLAD [27] 93.6 (90–108) No cognitive impairment: 317
Cognitive impairment: 465
Cognition No effect
Umeå 85+ study [26] 85, 90 and ≥ 95 No dementia: 342
Dementia: 233
Cognition
Dementia
Protective
Umeå 85+ study [25] 88.8 (±4.1) No incident dementia: 136
Incident dementia: 69
Incident dementia No effect
The 90+ Study [24] 93.2 (90–103) No incident dementia: 335
Incident dementia: 224
Incident dementia Risk
Vantaa 85+ Study [17] 88.4 (85.0–104.0) No incident dementia: 239
Incident dementia: 100
Incident dementia Equivocal
Absence of DM Leiden 85-plus Study [30] 85 (85) 596, dementia status unknown Cognition
Cognitive decline
Equivocal
Octabaix study [31] 85 (85) 167, dementia status unknown Cognition
Cognitive decline
No effect
Vantaa 85+ Study [11] ≥85 No incident dementia: 249
Incident dementia: 106
Incident dementia Protective
Absence of stroke H85 Gothenburg study [18] 85.7 (±0.05) No dementia: 794
Dementia: 271
Dementia Protective
Vantaa 85+ Study [32] 88.4 (±2.9) No dementia: 339
Dementia: 214
Incident dementia: 100
Dementia
Incident dementia
Protective
Absence of AF Vantaa 85+ Study [32] 88.4 (±2.9) No dementia: 339
Dementia: 214
Incident dementia: 100
Dementia
Incident dementia
No effect
Mood and sleep No depression Leiden 85-plus Study [34] 85 (85) 500, dementia status unknown Cognition Protective
Umeå 85+ study [14] 85, 90 and 95–103 No dementia: 173
Dementia: 69
Dementia Protective
High sleep quality PLAD [35] 93.5 (±3.4) No dementia: 251
Dementia: 409
Dementia
Cognition
Protective
Sensory system Absence of visual impairment Leiden 85-plus Study [37] 85 (85) 459, dementia status unknown Cognition Protective
Newcastle 85+ Study [38] 85 (85) No dementia: 771
Dementia: 68
Cognition Protective
Absence of glaucoma or cataract Newcastle 85+ Study [105] 85 (85) No dementia: 771
Dementia: 68
Cognition Equivocal
Absence of hearing impairment Leiden 85-plus Study [37] 85 (85) 459, dementia status unknown Cognition Equivocal
Physical performance and capacity Good physical performance Leiden 85-plus Study [40] 85 (85) 555, dementia status unknown Cognition Protective
The 90+ Study [41] 93.3 (±2.6) No incident dementia: 366
Incident dementia: 212
Incident dementia Protective
High physical activity The 90+ Study [16] 93 (90–103) No incident dementia: 319
Incident dementia: 268
Incident dementia No effect
Genetics Absence of APOEε4 and/or presence of APOEε2 Danish 1905 birth cohort [42] 93.1 (±0.3) 1551, dementia status unknown Cognition
Cognitive decline
No effect
Leiden 85-plus Study [43] 89.0 (87.4–91.2)b No dementia: 242
Dementia: 78
Dementia Protective
The 90+ Study [44] 93.7 (90–105) No dementia: 566
Dementia: 236
Incident dementia: 188
Dementia
Incident dementia
Equivocal
Vantaa 85+ Study [45] ≥85 313 without dementia
197 with dementia
Dementia Protective
Vantaa 85+ Study [46] ≥85 No incident dementia: 187
Incident dementia: 58
Incident dementia
Cognitive decline
No effect
MnSOD, GLRX, GSTP1, MT1A, NDUFV1, PRDX3, UQCRFS1, PICALM Danish 1905 birth cohort [106,107,108] 92-93c 1089–1650, dementia status unknown Cognition Protective
ACOX1 Danish 1905 birth cohort [106] 93.2 (92.7–93.8) 1089, dementia status unknown Cognition Risk
Cytokine genes, CLU Danish 1905 birth cohort [108,109,110] 92-93c 1380–1651, dementia status unknown Cognition
Cognitive decline
Equivocal
MTHFR, MTR Danish 1905 birth cohort [111] 93.1 (±0.3) 1651, dementia status unknown Cognition
Cognitive decline
No effect
KLOTHO PLAD [112] 93.5 (90–108) No cognitive impairment: 236
Cognitive impairment: 470
Cognition Protective
PPAR-γ2 PLAD [113] 93.7 (90–108) No cognitive impairment: 257
Cognitive impairment: 475
Cognition No effect
LRP, LPL, ACE Vantaa 85+ Study [114] ≥85 No dementia: 203
Dementia (AD): 113
Dementia No effect
Hallmarks of ageing Low level of inflammation markers Leiden 85-plus Study [49] 85 (85) No dementia: 491 Cognition
Cognitive decline
Equivocal
The 90+ Study [50] 94.3 (90–105) No dementia: 232
Dementia: 73
Dementia Equivocal
The 90+ Study [51] 93.9 (90–102) No incident dementia: 145
Incident dementia: 82
Incident dementia No effect
Low level of senescence markers Leiden 85-plus Study [52] 89.8 (85–101) No dementia: 452
Dementia: 146
Incident dementia: unknown
Cognition
Dementia
Incident dementia
No effect
Markers of neurodegeneration Normal levels of Aβ and tau in CSF H85 Gothenburg study [56] 85 (85) No incident dementia: 28
Incident dementia: 7
Incident dementia Protective
Negative amyloid PET-scan The 90+ Study [57] 94.2 (90–99)d No incident dementia: 10
Incident dementia: 3
Cognitive decline Protective
Less brain atrophy H85 Gothenburg study [58] 85 (85) No dementia: 30
Dementia: 23
Dementia Equivocal
Less WMH H85 Gothenburg study [59] 85 (85) No dementia: 133
Dementia: 103
Dementia Protective
High white matter integrity The 90+ Study [60] 94.6 (90–103) Normal: 64
CIND: 30
CIND No effect
  1. Amyloid β, AD Alzheimer’s disease, APOE Apolipoprotein E, CIND Cognitive Impairment, No Dementia, CSF cerebrospinal fluid, DM diabetes mellitus, HDL high-density lipoproteins, LDL low-density lipoproteins, MCI Mild Cognitive Impairment, MMSE Mini-Mental State Examination, N Number, PET positron emission tomography, PLAD Project of Longevity and Aging in Dujangyan, WMH white matter hyperintensities
  2. aMean age (range, if available, or ± if standard deviation) in years at baseline, unless stated otherwise; bMedian age (interquartile range, IQR) in years; cMinimal and maximum mean age in years of the studies referred to; dMedian age (range) in years