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Distinguishing Characteristics Identified Between Dementia With Lewy Bodies and Early-Onset Alzheimer Disease

More than 60% of patients with early-onset dementia with Lewy bodies had a least 3 of the 5 identified factors at first clinic visit, compared with fewer than 20% of those with early-onset Alzheimer disease.

For patients with early-onset dementia of an undifferentiated etiology, new research identified characteristics that may differentiate early-onset dementia with Lewy bodies (DLB) from early-onset Alzheimer disease (AD) cases, such as increased psychotics features, cognitive fluctuations, motor changes, and apathy.1

"This has important implications, as it suggests a thorough motor examination is critical when assessing early-onset dementia,” senior investigator Simon Kang Seng Ting, MD, Head of Service, Singapore General Hospital, and colleagues, wrote. "The limited range of neuropsychological tests used in this study could not consistently distinguish early-onset DLB from early-onset AD dementia. However, patients with late-onset DLB had more amnestic deficits than those with early onset, which we attribute to a higher burden of AD copathology."

A total of 1152 patients enrolled from the National Alzheimer’s Coordinating Center (NACC) database were included, 848 of whom received a pathological diagnosis of AD post mortem and 218 who received diagnosis of Lewy body disease. After excluding 52 patients with missing data and 12 diagnosed with Parkinson disease dementia, the remaining cohort were classified as either early-onset AD, early-onset DLB, and late-onset DLB based on age of symptom onset.

Based on these pathologically defined subgroups, data gathered at first clinic visit and post mortem were then analyzed retrospectively. These included demographic, cognitive, and motor and behavioral variables, which were collected on different forms under the first visit packet in the NACC database. Formal test batteries in the NACC database used included the Mini-Mental State Examination (MMSE), Unified Parkinson’s Disease Rating Scale, Geriatric Depression Scale (GDS), Neuropsychiatric Inventory Questionnaire (NPI-Q), Logical Memory IA and IIA, Trails A and B, and Boston Naming test.

After inclusion and exclusion criteria were applied, 363 patients with early-onset AD (mean age, 53.0 years; SD, 5.8), 32 patients with early-onset DLB (mean age, 57.9 years; SD, 3.2), and 147 patients with late-onset DLB remained (mean age, 73.5 years; SD, 5.5). Among patients with early-onset dementia, the initial clinical diagnosis concurred with the pathologic diagnosis in 79.9% (290 of 363) for pathologically confirmed AD but only 50% (16 of 32) of patients with pathologically confirmed DLB.

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Even after correcting for baseline MMSE and age differences between these 2 groups, early-onset DLB was more likely to present with visual hallucinations (46.9% vs 11.6%), delusional beliefs (18.8% vs 15.0%), apathy (71.9% vs 52.1%), and rapid eye movement sleep behavior disorder (15.6% vs 6.6%) than those with early-onset AD. These patients were also more likely to have motor symptoms including altered gait (62.5% vs 22.0%), tremors (53.1% vs 11.0), slowing (71.9% vs 26.2%), and increased falls (18.8% vs 8.0%) than those with early-onset AD.

Memory impairments, present in 87.5% and 96.7% of those with early-onset DLB and early-onset AD, respectively, was the predominant presentation for 46.9% and 63.1% of those respective groups. Essentially, those in the early-onset DLB group were more likely to report cognitive changes as the first sign of deterioration and to do worse on Logical Memory tests but not on Trails or Boston Naming. Additionally, those with early-onset DLB had higher GDS scores, although the frequency of reporting low mood was similar between the groups.

Using multivariate regression analyses, slowness, visual hallucinations, apathy, absence of agitation, and changes first observed in the motor domain were identified as the 5 factors that most specifically predicted a diagnosis of early-onset DLB over early-onset AD. Overall, 20 of 32 patients (63%) with early-onset DLB possessed at least 3 of these 5 factors at first clinic visit, compared with 57 of 363 patients (16%) with early-onset AD. Notably, 6 patients with early-onset DLB whose initial clinical diagnosis did not concur with their pathological diagnosis had received an accurate diagnosis when factoring these variables.

In the comparison between early-onset DLB and late-onset DLB, many of the factors were similar to those reported between early-onset AD and early-onset DLB, except for a few notable features. Although baseline MMSE scores were similar, late-onset DLB was characterized by more significant memory impairment and worse performance on neuropsychological test batteries than early-onset DLB. Those with early-onset DLB more frequently reported depressed mood and also higher GDS scores than those with late-onset DLB because of a higher incidence of mood-control medications. This association persisted even after correcting for prior use of mood medications.

1. Sim J, Li H, Hameed S, Ting S. Clinical manifestations of early-onset dementia with Lewy bodies compared with late-onset dementia with Lewy bodies and early-onset Alzheimer disease. JAMA Neurol. 2022;79(7):702-709. doi:10.1001/jamaneurol.2022.1133