Distinct neuropsychological presentation and progression between early‐ and late‐onset Alzheimer’s disease

Abstract

AbstractBackgroundEarly‐onset Alzheimer’s disease (EOAD, onset before 65 years), is the most common early‐onset neurodegenerative dementia. However, it still represents a diagnostic challenge especially when compared with late‐onset Alzheimer’s disease (LOAD). Our aim was to describe and compare the neuropsychological presentation at diagnosis and its progression in patients with EOAD and LOAD.MethodsOne‐hundred ninety‐five participants were included and classified accordingly to their CSF AD biomarker profile and clinical status: 46 young controls (Y‐CTR) aged below 65 years (age=57.4±4.7; MMSE=28.7±1.6), 23 old controls (O‐CTR) aged 65 or above (age=69.7±3.7; MMSE=28.0±1.4), 89 EOAD (age=59.8±4.2; MMSE=22.6±3.9) and 37 LOAD (age=74.5±4.8; MMSE=24.3±3.1). All subjects underwent clinical and neuropsychological assessment, APOE genotyping and lumbar puncture at baseline. Clinical and neuropsychological follow‐up was performed annually over 2 years.ResultsNo differences were found in terms of gender or years of education among the study groups. APOE4 was more frequent in EOAD and LOAD groups than controls (p<0.01). As expected, the control groups presented higher CSF Aβ42 and lower CSF tau and p‐tau levels than AD groups (Table 1). Baseline neuropsychological assessment (Figure 1) revealed differences between EOAD and LOAD in global cognitive function (p<0.05), ideomotor (p<0.05) and constructional (p<0.01) praxis, visuoperceptive (p<0.05) and visuospatial (p<0.01) function and working memory (p<0.05). When comparing controls and AD groups, EOAD performed significantly worse than Y‐CTR in all cognitive domains while LOAD showed differences with O‐CTR in memory, language and executive function but obtained a similar performance in ideomotor and constructional praxis, visuospatial function, attention and working memory. Longitudinally (Figure 2), no differences between EOAD and LOAD were observed on memory or language domains but EOAD showed higher decline in global cognitive function (p<0.05), ideomotor (p<0.05) and constructional (p<0.01) praxis, visuoperceptive (p<0.05) and visuospatial (p<0.01) function, attention (p<0.05) and working memory (p<0.05).ConclusionsEarly‐ and late‐onset AD present distinct neuropsychological profiles at diagnosis with EOAD displaying higher difficulties in non‐memory domains and a more aggressive course. The present data may help on enhancing EOAD diagnosis and therefore on ensuring an earlier intervention in this population.