Dryad
Therriault, Joseph;
Pascoal, Tharick;
Benedet, Andrea;
Fernandez-Arias, Jaime;
Wang, Tina;
Berzgin, Gleb;
Kang, Min Su;
Lussier, Firoza;
Chamoun, Mira;
Savard, Melissa;
Tissot, Cecile;
Massarweh, Gassan;
Soucy, Jean-Paul;
Vitali, Paolo;
Saha-Chaudhuri, Paramita;
Gauthier, Serge;
Rosa-Neto, Pedro
—
2021-12-17
<p style="text-align:justify;"><b>Objective:</b> <span style="background:white;"> To assess the frequency of biologically-defined Alzheimer’s disease (AD) in relation to age, sex and <i>APOEε4</i>, as well as rates of discordance between clinically- and biologically defined AD. </span></p>
<p style="text-align:justify;"><b>Methods:</b> <span style="background:white;">We assessed cognitively unimpaired (CU) elderly (n=166), amnestic MCI (n=77) and probable AD dementia (n=62) subjects who underwent evaluation by dementia specialists and neuropsychologists in addition to amyloi</span>d-PET with [<sup>18</sup>F]AZD4694<span style="background:white;"> and tau-PET with [<sup>18</sup>F]MK6240. Individuals were grouped according to their AD biomarker profile. Positive predictive value for biologically-defined AD was assessed in relation to clinical diagnosis. Frequency of AD biomarker profiles were assessed using logistic regressions with odds ratios and 95% CIs.</span></p>
<p style="text-align:justify;"><b>Results:</b> <span style="background:white;">The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically-defined AD (positive predictive value: 85.2%). 7.88% of CU elderly subjects were positive for both amyloid-PET and tau-PET. Frequency of biologically-defined AD increased with age (OR: 1.14; p<0.0001) and frequency of <i>APOEε4</i> allele carriers (Single <i>ε4: </i>OR: 3.82; <i>p</i><0.0001; Double <i>ε4: </i>OR: 17.55, <i>p</i><0.0001). </span></p>
<p style="text-align:justify;"><b>Discussion:</b> While we observed <span style="background:white;">strong, but not complete, agreement between clinically-defined “probable AD” dementia and biomarker positivity for both amyloid</span>-β<span style="background:white;"> and tau, we also observed that biologically-defined AD was not rare in CU elderly. A</span>bnormal tau-PET was almost exclusively observed in individuals with abnormal amyloid-PET. <span style="background:white;">Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically-defined AD and related entities. </span></p>