Background: Cases of early-onset Alzheimer disease (AD)with an autosomal dominant inheritance pattern (familial AD FAD ) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We des...Background: Cases of early-onset Alzheimer disease (AD)with an autosomal dominant inheritance pattern (familial AD FAD ) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, < 40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD. Objective: To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life. Design, Setting, and Participants: The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer’s Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD. Results: Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F)in exon 6 of the PSEN1 gene, which segregates with disease. Conclusions: A novel PSEN1 mutation causes very early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.展开更多
Objective: To quantify visual discrimination, spacem otion, and objectform perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). Methods: Th e...Objective: To quantify visual discrimination, spacem otion, and objectform perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). Methods: Th e authors used a crosssectional study to compare three demented groups matched for overall dementia severity (PDD: n=24; DLB: n=20; AD: n=23) and two age, s ex, and educationmatched control groups (PD: n=24, normal controls [NC]: n =2 5). Results: Visual perception was globally more impaired in PDD than in nondeme nted controls (NC, PD), but was not different from DLB. Compared to AD, PDD pati ents tended to perform worse in all perceptual scores. Visual perception of pati ents with PDD/DLB and visual hallucinations was significantly worse than in pati ents without hallucinations. Conclusions: Parkinson disease dementia (PDD) is as sociated with profound visuoperceptual impairments similar to dementia with Lewy bodies (DLB) but different from Alzheimer disease. These findings are consisten t with previous neuroimaging studies reporting hypoactivity in cortical areas in volved in visual processing in PDD and DLB.展开更多
文摘Background: Cases of early-onset Alzheimer disease (AD)with an autosomal dominant inheritance pattern (familial AD FAD ) are rare but have greatly advanced our understanding of the molecular pathogenesis of AD. We describe herein a kindred with very early-onset FAD (age, < 40 years) with unusual pathological features and a novel mutation in the presenilin 1 (PSEN1) gene (S170F) and review the existing literature on very early-onset FAD. Objective: To analyze the neuropathological and genetic features of a family with onset of AD in the third decade of life. Design, Setting, and Participants: The proband underwent full clinical assessment and postmortem examination at the Washington University Alzheimer’s Disease Research Center, St Louis, Mo. Limited pathological samples and autopsy records of 2 affected family members were available. The proband underwent screening for mutations in genes linked with FAD. Results: Dementia developed in 3 family members in this kindred at a mean age of 27 years; the proband had myoclonus, seizures, and rigidity, similar to findings in previously described kindreds with PSEN1 mutations. All 3 family members were confirmed to have AD by neuropathological examination. The proband also had widespread Lewy body pathology in the brainstem, limbic areas, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. The proband had a single mutation (S170F)in exon 6 of the PSEN1 gene, which segregates with disease. Conclusions: A novel PSEN1 mutation causes very early-onset FAD with associated Lewy bodies. To our knowledge, this kindred has the earliest reported onset of pathologically confirmed FAD and dementia with Lewy bodies.
文摘Objective: To quantify visual discrimination, spacem otion, and objectform perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). Methods: Th e authors used a crosssectional study to compare three demented groups matched for overall dementia severity (PDD: n=24; DLB: n=20; AD: n=23) and two age, s ex, and educationmatched control groups (PD: n=24, normal controls [NC]: n =2 5). Results: Visual perception was globally more impaired in PDD than in nondeme nted controls (NC, PD), but was not different from DLB. Compared to AD, PDD pati ents tended to perform worse in all perceptual scores. Visual perception of pati ents with PDD/DLB and visual hallucinations was significantly worse than in pati ents without hallucinations. Conclusions: Parkinson disease dementia (PDD) is as sociated with profound visuoperceptual impairments similar to dementia with Lewy bodies (DLB) but different from Alzheimer disease. These findings are consisten t with previous neuroimaging studies reporting hypoactivity in cortical areas in volved in visual processing in PDD and DLB.
