Neuropathological lesions in the very old: results from a large Brazilian autopsy study

Abstract

Objective: To compare neuropathological correlates of cognitive impairment between very old and younger individuals from a Brazilian clinicopathological study.

Methods: We assessed the frequency of neuropathological lesions and their association with cognitive impairment (Clinical Dementia Rating scale ≥0.5) in the 80 or over age group compared to younger participants, using logistic regression models adjusted for sex, race and education.

Results: Except for infarcts and siderocalcinosis, all neuropathological lesions were more common in the 80 or over age group (n = 412) compared to 50-79 year olds (n = 677). Very old participants had more than twice the likelihood of having ≥2 neuropathological diagnoses than younger participants (OR = 2.66, 95% CI = 2.03-3.50). Neurofibrillary tangles, infarcts and hyaline arteriolosclerosis were associated with cognitive impairment in the two age groups. Siderocalcinosis was associated with cognitive impairment in the younger participants only, while Lewy body disease was associated with cognitive impairment in the very old only. In addition, we found that the association of infarcts and multiple pathologies with cognitive impairment was attenuated in very old adults (Infarcts: P for interaction = 0.04; and multiple pathologies: P = 0.05). However, the predictive value for the aggregate model with all neuropathological lesions showed similar discrimination in both age groups [Area under Receiver Operating Characteristic curve (AUROC) = 0.778 in younger participants and AUROC = 0.765 in the very old].

Conclusion and relevance: Despite a higher frequency of neuropathological findings in the very old group, as found in studies with high-income populations, we found attenuation of the effect of infarcts rather than neurofibrillary tangles and plaques as reported previously.

Keywords: 80 and over; Alzheimer’s disease; aged; dementia; neuropathology; vascular dementia; very old.

Figure 1

Relative frequency of participants aged under 80 years (black bar) and those aged 80 years or older (white bar) according to the number of neuropathological lesions present in the individual.

Figure 2

Percentage of single and multiple pathologies within each age group in participants aged under 80 years (black bar) and those aged 80 years or older (white bar). A. Alzheimer’s disease (AD) lesions (Braak & Braak score for neurofibrillary tangles ≥III and CERAD score ≥B) alone and in combination with vascular lesions, Lewy body disease (LBD), argyrophilic grain (AG), siderocalcinosis (sidero) and TDP‐43. B. Vascular lesions (infarcts and small vessel disease) alone and in combination with LBD, AG, siderocalcinosis and TDP‐43. Chi‐square test for the association between each combination of neuropathological lesions and age groups: *P < 0.0001; **P < 0.001; ***P < 0.05.

Figure 3

Relative frequency of moderate or severe neuropathological lesion in participants with cognitive impairment (triangle marker) and those without cognitive impairment (square marker), according to age group (<80 yo and ≥80 yo): A. Neurofibrillary tangles (Braak & Braak score ≥ III); B. Neuritic plaques (CERAD ≥ B); C. Infarcts; D. Hyaline arteriolosclerosis; E. Cerebral amyloid angiopathy; F. Lewy body disease (LBD) (Braak & Braak LBD ≥ IV); G. Siderocalcinosis; H. Argyrophilic grain disease; I. Hippocampal sclerosis; J. transactive response DNA‐binding protein 43 kDA (TDP‐43). Information for TDP‐43 was available in 410 participants. P‐values are for the interaction term between each neuropathological lesions and age group.

Figure 4

Discrimination of the aggregate model with neuropathological lesions in participants younger than 80 years (gray line with triangle marker) and 80 years and older (black line with circle marker) using the area under the Receiving Operator Curve (ROC). The aggregate model includes neurofibrillary tangles, neuritic plaques, Lewy body disease, infarcts, hyaline arteriolosclerosis, cerebral amyloid angiopathy, siderocalcinosis, hippocampal sclerosis and argyrophilic grain disease.