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

According to the Alzheimer’s Association, Lewy body dementia is thought to be the third most common form of Alzheimer's, accounting for between 5 - 10 % of all cases. Despite this, according to the researchers of this paper published in Jama Neurology on the 23rd of May 2022, early-onset dementia with Lewy bodies remains under-researched, and misdiagnosis is common.

They set out to establish whether there were appreciable clinical differences in presentation between early-onset dementia (DLB) with Lewy bodies, late-onset dementia with Lewy bodies and early-onset Alzheimer's dementia AD). Early-onset DLB was defined as dementia having been diagnosed at 65 years or younger.

Study Method and Design

The research  - a retrospective case-control study - extracted records of those patients who had DLB, which had been confirmed post-mortem, and patients with AD who were enrolled in the National Alzheimers Coordinating Center from the period of January 2005 to July 2017. 

A total of 1152 patients with all forms of dementia were then sampled: 848 had a post-mortem diagnosis of AD, and 218 of Lewy body disease. 52 patients were excluded as their data was incomplete, together with 12 patients who had dementia due to Parkinson's disease  The patients were “....classified by age of symptom onset into early-onset AD, early-onset DLB, and late-onset DLB subgroup”², and data was extracted from June to December 2018 and November to December 2021.

The researchers then analysed and compared the initial diagnosis of dementia and the final pathological diagnosis, including time to death.

Findings 

Of the original sample of 542 individuals:

- 363 were categorised as having early-onset AD. These patients had a mean age of 53 [5.8yrs] and 57.3% were male
- 32 had early-onset DLB – they had a mean age of 57.9 [3.2yrs)and 71.9% were male
- 147 had late-onset DLB, were 73.5 years of age [5.5yrs} and 70.1% were male. 

The results determined that early-onset DLB had been misdiagnosed in at least 50% of cases 

Specifically as to the differences in clinical presentation which was the stated objective of the research:

“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 behavioural 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.” ²

Conclusions

The above findings illustrated that there were clearly distinguishable features which differentiated early-onset DLB from early-onset AD. Practitioners should, therefore, asses for “motor signs, apathy, depression, and determine if motor deterioration predated cognitive and behavioural changes before making a diagnosis.^”2

In relation to late-onset DLB, the presence of amnestic features which are commonly seen in late-onset DLB may be associated with Alzheimer's disease co-pathology and further investigation is therefore warranted before making the diagnosis.²

Sim J, Li H, Hameed S, Ting SKS. Clinical Manifestations of Early-Onset Dementia With Lewy Bodies Compared With Late-Onset Dementia With Lewy Bodies and Early-Onset Alzheimer Disease. JAMA Neurol. Published online May 23, 2022. doi:10.1001/jamaneur