Cerebral amyloid deposition itself is not related to depressive symptoms in elderly individuals with normal cognition, MCI, and Alzheimer's disease


      A couple of population studies demonstrated that elderly with depression have lower plasma amyloid-β 42 (Aβ42) than those without depression, and so called “amyloid depression hypothesis” (i.e., the hypothesis that cerebral amyloid deposition is related to late-life depression) was proposed. This study aimed to investigate the relationship between global cerebral Aβ burden and depressive symptoms in elderly individuals with normal cognition (NC), amnestic mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD).


      Twenty-six NC, 23 MCI and 27 AD individuals were recruited. Subjects with history of major depressive episode or stroke were excluded. All subjects received three-dimensional volumetric 3T MRI, Pittsburgh Compound B (PiB)-positron emission tomography (PET) and comprehensive clinical evaluation including vascular burden assessment. Depressive symptoms were measured using Geriatric Depression Scale (GDS) and Hamilton Depression Rating Scale (HAM-D).


      There were significant group differences of GDS and HAM-D scores among diagnostic groups, and post-hoc tests showed that AD had significantly higher GDS and HAM-D scores than NC (see Table). However, multiple linear regression analysis controlling for age, gender, diagnostic group, and vascular burden did not reveal that global cerebral Aβ burden measured by PiB-PET was associated with GDS or HAM-D scores. In subgroup analyses for each diagnostic group, we did not find any significant associations between global cerebral Aβ burden and GDS or HAM-D scores after controlling age, gender and vascular burden.


      Our results did not support “amyloid depression hypothesis”, while the relationship between diagnostic group and depression scores implied that late-life depression might be associated with overall brain degeneration.
      Table 1Subjects characteristics
      All (n=76)CN (n=26)MCI (n=23)AD (n=27)P
      Age, year70.32±7.3671.541 5.2970.481 7.6669.00+ 8.740.457
      Gender, n (M/F)18/5810/164/194/230.090
      Education, year9.28±4.8911.1214.678.87+4.637.85+4.930.045*
      ApoE ε4 carrier, n (%)37 (48.7)12 (46.2)10 (43.5)15 (55.6)0.662
       ≥ 1120012
      Vascular risk score, %0.96+0.740.85+0.731.09+0.730.96+0.760.529
      Global amyloid burden1.3110.321.09+0.221.31+0.281.54+0.29<0.001*†
      PiB positive, n (%)35 (46.1)3 (11.5)11 (47.8)21 (77.8)<0.001
      CDR-SOB, clinical dementia rating-sum of boxes; GDS, Geriatric depression scale; HAM-D, Hamilton depression rating scale. Comparison of three diagnostic groups was done by ANOVA with post hoc contrasts using Tukey's methods: *CN vs AD, †MCI vs AD, ‡CN vs MCI. Chi-square test was performed to compare the categorical variables