RESUMEN
BACKGROUND: Little is known regarding the differential effects of the apolipoprotein E (APOE) É4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). OBJECTIVE: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEÉ4 allele and onset age. METHODS: A total of 165 participants including 54 EOAD patients (29 É4-; 25 É4+), 45 LOAD patients (21 É4-; 24 É4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. RESULTS: EOAD É4- patients showed greater THK retention in the association cortices, whereas their EOAD É4+ counterparts had more retention in medial temporal areas. THK topography of LOAD É4+ was similar to EOAD É4â+â. THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD É4-, highest in LOAD É4-, and modest in É4+ groups. Even in the APOEÉ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD É4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. CONCLUSION: Our observations suggest the differential effects of the APOEÉ4 on the relationship between tau and amyloid in EOAD and LOAD.
Asunto(s)
Enfermedad de Alzheimer , Humanos , Alelos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Cognición , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To evaluate the differences between early-onset subcortical vascular cognitive impairment (EO-SVCI) and late-onset subcortical vascular cognitive impairment (LO-SVCI) with regard to pathologic burden, structural changes, and cognitive function. METHODS: We prospectively recruited 142 patients from a single referral center. Patients were divided into EO-SVCI (n = 30, age at onset <65 years) and LO-SVCI (n = 112, age at onset ≥ 65 years) groups. All patients underwent neuropsychological tests, 3T brain MRI, and [(11)C] Pittsburgh compound B (PiB)-PET. We compared pathologic burden such as small vessel disease and amyloid burden; structural changes such as structural network, cortical thickness, and hippocampal volume; and cognitive function between EO-SVCI and LO-SVCI. RESULTS: EO-SVCI patients had more lacunes, while LO-SVCI patients had higher PiB standardized uptake value ratios. EO-SVCI patients exhibited more severe structural network disruptions in the frontal area, while LO-SVCI patients exhibited more severe cortical and hippocampal atrophy. Although disease severity did not differ between the 2 groups, frontal-executive dysfunction was more severe in EO-SVCI patients. CONCLUSIONS: EO-SVCI patients showed more vascular related factors, while LO-SVCI patients exhibited more Alzheimer disease-related characteristics. The greater number of lacunes in EO-SVCI might account for the more severe frontal network disruption and frontal-executive dysfunction, while the greater amyloid burden in LO-SVCI might account for the more severe cortical and hippocampal atrophy. Our findings suggest that the age at onset is a crucial factor that determines distinct features in SVCI patients, such as pathologic burden, structural changes, and cognitive function.