Abstract

ObjectiveTo further our understanding of the association between self-reported childhood learning disabilities (LDs) and atypical dementia phenotypes (Atypical Dementia), including logopenic primary progressive aphasia (L-PPA), Posterior Cortical Atrophy (PCA), and Dysexecutive-type Alzheimer’s Disease (AD).MethodsThis retrospective case series analysis of 678 comprehensive neuropsychological assessments compared rates of self-reported LD between dementia patients diagnosed with Typical AD and those diagnosed with Atypical Dementia. 105 cases with neuroimaging or CSF data available and at least one neurology follow-up were identified as having been diagnosed by the neuropsychologist with any form of neurodegenerative dementia. These cases were subject to a consensus diagnostic process among three dementia experts using validated clinical criteria for AD and PPA. LD was considered Probable if two or more statements consistent with prior LD were documented within the Social & Developmental History of the initial neuropsychological evaluation.Results85 subjects (Typical AD n=68, Atypical AD n=17) were included in the final analysis. In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD (OR 13.1, 95% CI 1.3-128.4). All three of the L-PPA cases reporting a childhood LD endorsed childhood difficulty with language. By contrast, both PCA cases reporting Probable childhood LD endorsed difficulty with attention and/or math.ConclusionsIn people who develop dementia, childhood LD may predispose to atypical phenotypes. Future studies are required to confirm whether atypical neurodevelopment predisposes to regional-specific neuropathology in AD and other dementias.

Highlights

  • Adults with a childhood history of specific learning disabilities (LDs) may be more likely to develop atypical phenotypes of dementia, including atypical Alzheimer’s Disease (AD) [1,2,3]

  • In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD

  • Future studies are required to confirm whether atypical neurodevelopment predisposes to regional-specific neuropathology in AD and other dementias

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Summary

Introduction

Adults with a childhood history of specific learning disabilities (LDs) may be more likely to develop atypical phenotypes of dementia, including atypical Alzheimer’s Disease (AD) [1,2,3]. Atypical AD phenotypes involve focal, primarily non-amnestic presentations, with symptoms that correlate with non-hippocampal tau pathology [5]. When logopenic Primary Progressive Aphasia (L-PPA) is caused by AD pathology, it begins with word-finding difficulty at onset, with tau-related neurodegeneration prominent in language associational cortex [6]. Posterior Cortical Atrophy (PCA) and “Dysexecutive” variants of AD involve visual and dysexecutive symptoms at onset, with prominent neurodegeneration found in visual and frontal association cortices, respectively [7,8,9,10,11]. Non-AD dementia syndromes caused by frontotemporal lobar dementia (FTLD) pathology, including Semantic Dementia (SD), behavioral variant FTD (bvFTD) and non-fluent/agrammatic Primary Progressive Aphasia (aPPA), exhibit significant phenotypic heterogeneity [12]

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