The Combination of Plaques and Tangles Indicates a Much Higher Risk of Dementia
Medical imaging allows researchers to assess the burden of amyloid-β and tau deposits in the living brain. As noted here, it is the combination of both amyloid plaques and tau tangles that marks a greatly raised risk of the onset of cognitive decline and dementia, 20-fold higher in fact. This is a very large effect size, suggesting that the interaction of multiple mechanisms is the important driver of neurodegeneration in tauopathies such as Alzheimer's disease.
Do amyloid plaques and tau tangles destine a cognitively intact person to decline? Yes, according to researchers who report that cognitively normal older adults with plaques and tangles declined much faster than those without either pathology - and faster than those with only plaques. Over an average of 3.5 years of follow-up, people with plaques and tangles as measured by PET had a 15 to 20 times higher risk of developing mild cognitive impairment (MCI) or dementia. Other groups analyzing different cohorts appear to be finding the same thing; papers are under review. "This quick progression to MCI is clinically relevant because it tells us that amyloid and tau PET are predictive of imminent cognitive decline. To consider amyloid and tau PET positivity merely as a risk factor, and not manifest disease, may be an underestimation of its malignancy."
Researchers pooled data from 1,325 cognitively intact older adults from seven longitudinal research cohorts and divided them into groups based on their amyloid and tau PET scans: 843 had neither pathology, 328 had only amyloid (A+T-), 55 had amyloid with tau in the medial temporal lobe (A+T+MTL), and 65 had amyloid with tau in the neocortex as well (A+T+Neo). 80 percent of the neocortical-positive participants also had tangles in their MTL, as tau generally spreads from the MTL to the cortex. The researchers tracked scores on the modified preclinical Alzheimer cognitive composite 5 (mPACC5) and Mini-Mental State Exam (MMSE) for an average of 3.5 years after the PET scans. Biomarker-positive participants were an average of seven years older, and had slightly lower baseline MMSE scores, than their biomarker-negative counterparts. While controls held their ground on the mPACC5 and MMSE, A+T- participants slipped a tad and both A+T+ groups declined steeply.
People with plaques and tangles were likelier to develop MCI or dementia. Compared to controls, A+T- volunteers had a 2.5-fold higher risk of developing MCI, while people with A+T+MTL or A+T+Neo had 15 or 19 times higher risk, respectively. Twenty-one people progressed to all-cause dementia; half were A+T+Neo. They were a whopping 40 times likelier to develop dementia in this time frame than controls, while A+T+MTL people had a 5.5-fold higher risk. A+T- volunteers developed dementia at the same rate as controls.