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. 2016 Apr 5;6(4):e775.
doi: 10.1038/tp.2016.39.

Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns

M Habes  1   2   3 , D Janowitz  3 , G Erus  2 , J B Toledo  4 , S M Resnick  5 , J Doshi  2 , S Van der Auwera  3 , K Wittfeld  6 , K Hegenscheid  7 , N Hosten  7 , R Biffar  8 , G Homuth  9 , H Völzke  1 , H J Grabe  3   6 , W Hoffmann  1   6 , C Davatzikos  2
Affiliations

Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns

M Habes et al. Transl Psychiatry. .

Abstract

We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

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Figures

Figure 1
Figure 1
SPARE-BA values for all SHIP participants (n=2705) plotted against age. Red line represents local polynomial fitted curve. Higher/lower values indicate less/more aging-specific brain atrophy patterns, captured by the SPARE-BA index. Brain rendering shows the gray matter RAVENS (regional volumetric) maps for age groups 20–80. The color map represents lower RAVENS values (that is, less gray matter) in blue and higher RAVENS values (that is, more gray matter) in red. We observe a consistent decrease in gray matter volume in the cortex with age, which are particularly prominent in certain frontal, parietal and temporal brain regions. SPARE-BA, Spatial Pattern of Atrophy for Recognition of BA.
Figure 2
Figure 2
(a) SPARE-BA index for SHIP subjects ⩾65 years old. Values are reflecting relatively continuous progression of aging-related atrophy patterns with age. Based on SPARE-BA, we grouped these subjects into subjects with advanced brain aging (red dots; 0.5 s.d. below trend line) and resilient to brain aging (black triangles; 0.5 s.d. above trend line). (b) The relationship between age and SPARE-AD (reflecting clinical AD-like patterns of brain atrophy) in both groups. Advanced brain aging individuals have higher SPARE-AD values. SPARE-AD, Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease; SPARE-BA, Spatial Pattern of Atrophy for Recognition of BA.
Figure 3
Figure 3
Regional gray matter volume differences between resilient aging (n=191) and advanced aging (n=179) subjects. Results are significant at level P<0.001, and all survived FDR correction with q<0.001. FDR, false discovery rate.
Figure 4
Figure 4
Patterns overlap. Blue: regions displaying significant regional atrophy patterns between resilient and ABA individuals; Red: regions displaying significantly AD-related patterns of atrophy in high vs low SPARE-AD individuals; Green: overlap of the blue and red regions (P<0.001 and FDR correction with q<0.001). Histograms are presented for gray matter volumes of blue/red/green regions for ABA and RA individuals. These results highlight the difference between advanced and clinical AD-like brain aging, and they also indicate that increased SPARE-AD values in advanced aging are entirely due to partial overlap (green) of underlying regions. ABA, advanced brain aging; FDR, false discovery rate; RA, resilient to aging; SPARE-AD, Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease.
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