Clinical Manifestations of Early-Onset Dementia With Lewy Bodies Compared With Late-Onset Dementia With Lewy Bodies and Early-Onset Alzheimer Disease

Abstract

IMPORTANCE Early-onset dementia, presenting in individuals younger than 65 years, is a diagnosis with significant social and financial implications. The early-onset form of dementia with Lewy bodies (DLB) is poorly understood. OBJECTIVE To investigate clinical features that distinguish early-onset DLB (onset and diagnosis at age <65 years) from late-onset DLB (onset at age Ն65 years) and from early-onset Alzheimer disease (AD) dementia. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective case-control study on patients with pathologically confirmed DLB or AD enrolled in the National Alzheimer's Coordinating Center database from January 2005 to July 2017. The National Alzheimer's Coordinating Center Uniform Data Set comprised deidentified data collected by Alzheimer disease centers in the United States. Of patients fulfilling criteria for all-cause dementia at enrollment (n = 1152), those who at post mortem received a pathological diagnosis of either AD (n = 848) or Lewy body disease (n = 218) were selected. Excluding 52 patients owing to missing data and 12 diagnosed with Parkinson disease dementia, remaining patients were classified by age of symptom onset into early-onset AD, early-onset DLB, and late-onset DLB subgroups. Data were analyzed from June to December 2018 and from November to December 2021. EXPOSURES Demographics, cognitive, behavioral, and motor features recorded at first clinic visit and neuropathological characteristics at autopsy were analyzed by disease subgroup. MAIN OUTCOMES AND MEASURES Concordance between initial etiologic diagnosis of dementia and final pathological diagnosis was assessed, as was time to death. RESULTS A total of 542 individuals were categorized as having early-onset AD (n = 363; mean [SD] age, 53.0 [5.8] years; 208 [57.3%] male), early-onset DLB (n = 32; mean [SD] age, 57.9 [3.2] years; 23 [71.9%] male), and late-onset DLB (n = 147; mean [SD] age, 73.5 [5.5] years; 103 [70.1%] male). Early-onset DLB was clinically misdiagnosed in 16 individuals (50%). Features that predicted a diagnosis of early-onset DLB over early-onset AD included visual hallucinations (15 [46.9%] vs 42 [11.6%]), slowness (23 [71.9%] vs 95 [26.2%]), apathy (23 [71.9%] vs 189 [52.1%]), and motor deterioration that preceded cognitive and behavioral symptoms (7 [21.9%] vs 6 [1.7%]). Late-onset DLB had more amnestic features, but this was accounted for by a higher proportion of neocortical neuritic plaques and diffuse plaques (frequent in 79 [53.7%] vs 8 [25%]) than seen in early-onset DLB.CONCLUSIONS AND RELEVANCE This study found that early-onset DLB has clinical features that distinguish it from early-onset AD, whereas features of late-onset DLB are associated with a higher burden of AD copathology.

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with Lewy bodies

“…Of note, subclinical depressive symptoms in ageing are linked with neurodegeneration biomarkers in the precuneus, PCC and fronto-temporal regions [27]. Previous studies reported the presence and intensity of depressive mood speci cally characterized the clinicopathological cohort of EO-DLB [5]. While we did not nd differences between EO and LO-DLB in neuropsychiatric presentations, depression, and apathy can be observed and linked to the above-reported evidence when a large cohort of subjects would be included.…”

“…Early onset (EO) dementia refers to a condition starting before the age of 65, often characterized by more marked behavioral and psychiatric symptoms, and a higher mortality than late-onset (LO) dementia [2]. EO and LO dementia with Lewy bodies (DLB) are similar in terms of core clinical symptoms (i.e., visual hallucinations, parkinsonism, uctuating cognition, and REM sleep behavior disorder (RBD) [3,4], however, LO-DLB present more severe memory de cits than EO-DLB, while EO-DLB has a quicker decline and neuropsychiatric features at the beginning [5]. The EO-DLB has been poorly investigated yet, however, some speci c prodromal clinical features are reported, namely a history of depression that can predate an early onset of DLB [6].…”

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with lewy bodies

“…A recent clinicopathological study showed that EO-DLB and LO-DLB are largely similar in core symptoms and with a comparable distribution of limbic and neocortical Lewy pathology [5]. However, LO-DLB patients present more amnestic de cits that were accounted for by AD co-pathology, and EO-DLB can be predated by history of depression [5]. The present study shows similarities between EO-DLB and LO-DLB in terms of clinical core symptom presentations and major brain hypometabolism hallmarks.…”

“…EO and LO dementia with Lewy bodies (DLB) are similar in terms of core clinical symptoms (i.e., visual hallucinations, parkinsonism, uctuating cognition, and REM sleep behavior disorder (RBD) [3,4], however, LO-DLB present more severe memory de cits than EO-DLB, while EO-DLB has a quicker decline and neuropsychiatric features at the beginning [5]. The EO-DLB has been poorly investigated yet, however, some speci c prodromal clinical features are reported, namely a history of depression that can predate an early onset of DLB [6].…”

LoC-SERS Platform Integrated with the Signal Amplification Strategy toward Parkinson’s Disease Diagnosis

“…Parkinson’s disease (PD) is a common chronic progressive neurodegenerative disease, ranking as the second most common neurodegenerative disease only after Alzheimer’s disease. − The exact cause of PD is still unclear, and most scholars currently believe that PD is pathologically related to the degeneration of dopamine neurons in the substantia nigra . Nowadays, the diagnosis of PD currently relies on medical history and clinical symptoms.…”