Measurement of beta-amyloid (Aβ) and phosphorylated tau (p-tau) levels offers the
potential for early detection of neurocognitive impairment. Still, the probability
of developing a clinical syndrome in the presence of these protein changes (A+ and
T+) remains unclear. By performing a systematic review and meta-analysis, we investigated
the risk of mild cognitive impairment (MCI) or dementia in the non-demented population
with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal
fluid examination.A systematic search of prospective and retrospective studies investigating
the association of Aβ and p-tau with cognitive decline was performed in three databases
(MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was
assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were
pooled using a random-effects model. The effect of neurodegeneration was not studied
due to its non-specific nature.A total of 18,162 records were found, and at the end
of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to
the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients
was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia
was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aβ42 or Aβ42/40 analysis and amyloid
PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects
(11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73
[95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95%
CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion
(13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression
showed that the ORs for Aβ exposure decreased with age in MCI. (beta = -0.04 [95%
CI -0.03 to -0.083]).Identifying Aβ-positive individuals, irrespective of the measurement
technique employed (CSF or PET), enables the detection of the most at-risk population
before disease onset, or at least at a mild stage. The inclusion of tau status in
addition to Aβ, especially in A+T+ cases, further refines the risk assessment. Notably,
the higher odds ratio associated with Aβ decreases with age.The study was registered
in PROSPERO (ID: CRD42021288100).
