Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer’s disease, with an estimated prevalence according to different studies between 2% and 25% of all cases (Vann Jones and O’Brien, 2014).

What is Lewy body dementia?

This neurodegenerative disease is mainly characterized by the accumulation of Lewy bodies, mostly formed by alpha-synuclein proteins, in subcortical regions such as the substantia nigra, locus ceruleus, basal nuclei of Meynert and hypothalamus, as well as in the frontal, temporal cortex, and occipital lobes. However, neither the neuropathology, nor the classification, nor the naming of neurodegenerative dementias are simple matters; for example, alongside deposits of alpha-synuclein there are deposits of p-Tau and beta-amyloid protein, i.e., typical findings of Alzheimer’s disease.

Classification of dementias

In Figure 1, extracted from an article with a more than suggestive title, “Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing ‘where’ by ‘what'” (Allegri, 2020), we can see a classification of neurodegenerative dementias according to the proteins associated with each of them.

Symptoms of dementia due to Lewy bodies

Before entering fully into the description of the alterations of higher visual processing in patients with dementia with Lewy bodies, and in order to get a general idea of their clinical profile, let us contextualize them within the set of signs usually collected by the literature as characteristic of this population. Briefly, and according to The Dementia with Lewy Bodies (DLB) Consortium (McKeith et al., 2017), these would be:

• Visual hallucinations.
• Extrapyramidal signs.
• Fluctuation of cognitive status and arousal, in appearance, similar to delirium.
• Anxiety, depression, delusions and sleep disturbance.
• Prominent cognitive impairment of executive functions, attention, visuoperceptual and visuospatial functions, and, in some publications, visuoconstructive deficits are also included.

Differences between Lewy body dementia and Alzheimer’s disease

Regarding cognitive aspects, much of the information available on the neuropsychological profile of patients with Lewy body dementia comes from comparative studies or studies aimed at facilitating differential and early diagnosis between this and Alzheimer’s disease (AD), since they share some similarities in their initial phase.

One of the similarities usually referred to is the impairment of episodic memory, although, if we go into detail, this similarity is not such, since patients with DLB in mild or prodromal stages show the difficulties at the time of information retrieval, improving their performance through the use of cues and recognition of previously presented information, and with little presence of intrusions and false positives, as opposed to the predominant deficit in the encoding process and the commission of numerous intrusions and false positives that characterizes AD (Guidi et al. , 2006; Petrova et al., 2016).

In any case, the neuropsychological findings that best define and differentiate Lewy body dementia in its prodromal and mild phases, with respect to other dementias and normal aging, are the attentional, executive, visuospatial and visuoperceptual deficits, which stand out with respect to the state of the rest of cognitive functions (Gurnani and Gavett, 2017; Kemp et al., 2017). In fact, regarding visuoperceptive deficits, it could be said that, if amnesia is the characteristic sign of AD, visual agnosias could be the characteristic sign of MCI (Ferman et al., 2006; Collerton, et al., 2003).

Focusing on visuospatial and visuoperceptive deficits, it is estimated that about 70% of patients with Lewy body dementia, as opposed to 40% of Alzheimer’s patients, present them from the onset of the disease (Wood et al., 2013a).

Visuoperceptive alterations

In the case of visuoperceptual deficits, it has been observed that patients with DLB present difficulties both in simple tasks of size, shape and color discrimination, i.e., difficulties that could be categorized as visual pseudoagnosia according to the classic model of Warrington and Rudge (1995), as well as in complex tasks that involve a deeper integration and analysis of visual information, for example, object recognition tasks in both canonical and foreshortened positions, identification of superimposed figures, object recognition from a fragment of an object, recognition of fragmented letters, discrimination of real objects from non-objects, or identification of objects from their silhouette (Yokoi et al. , 2014), i.e., integration apperceptive agnosia and, on a lesser average, spatial transformation agnosia, as modeled by Humphreys and Riddoch (2013).

In addition, difficulties in copying both simple and complex figures, i.e., possible visuoconstructive impairments, have also been documented (Kemp et al., 2017). However, in the latter case, a meticulous neuropsychological exploration by processes should be considered to refine a syndromic differential diagnosis to clarify whether the difficulties in copying figures are due to a constructive apraxia, or, on the contrary, are caused by the visuoperceptive, visuospatial and/or executive difficulties characteristic of patients with Lewy body dementia.

Visuospatial alterations

Regarding visuospatial deficits, in patients with MCI, difficulties have been described in activities that require identifying the spatial relationship between various visual stimuli, discriminating the angle between lines, performing scanning or visual search, counting stimuli, motion perception, fitting figures or pieces in 2D, or mentally rotating objects in 3 dimensions.

Actually, there is fairly widespread agreement in the description of visuoperceptual and visuospatial difficulties observed in patients with Lewy body dementia since, the vast majority of the available publications on this issue in which these signs have been used have been explored or assessed using the Visual Object and Spatial Perception Battery (VOSP), superimposed figure tasks and the Hooper Visual Organization Test (Tröster, 2008; Oda et al…, 2009; Li et al., 2014, Mitolo et al., 2016). A fact that could be taken as a sample of the very limited variety of neuropsychological tests available for the assessment of deficits in higher processing of visual information.

Screening for dementia with Lewy bodies

To the intrinsic value of early detection, characterization and quantification of cognitive impairment in patients with dementia with Lewy body disease we must add a not inconsiderable added value. Deficits in higher visual information processing may play an important role as prognostic indicators of the evolution of DLB patients. For example, those patients classified as non-amnestic multidomain mild cognitive impairment that includes visuoperceptual and visuospatial deficits are at greater risk of progressing to Lewy body dementia than those classified as amnestic mild cognitive impairment, who are more likely to progress to Alzheimer’s disease (Donaghy and McKeith, 2014).

In addition, those patients who present early with visuospatial deficits are likely to show a more rapid decline in both their ability to perform basic and instrumental activities of daily living and their overall cognitive status (Hamilton et al., 2008; Wood et al., 2013b).

And finally, the relationship between visuoperceptive deficits and visual hallucinations should be highlighted, since the greater the severity of the former as a sign of impairment of visual association areas, the greater the risk of visual hallucinations appearing a posteriori. And the latter is very important, because visual hallucinations are one of the key signs for the differential diagnosis of DLB versus AD, so early detection of visual agnosias can warn us of what may happen later (Auning et al., 2011).

Neuroanatomical characteristics

In parallel to the study of the neuropsychological profile of patients with mild or prodromal Lewy body dementia, knowledge has been accumulating on the neuroanatomical features of this disease.

Its differentiating features include signs of early atrophy in the posterior cingulate cortex and in superior temporo-occipital and orbitofrontal regions, together with functional alterations in brain regions necessary for visual information processing, such as the occipital cortex and occipitoparietal visual association areas (Donaghy and McKeith, 2014; Mak et al., 2014; Yousaf et al., 2019). Along with the above, we should also include the impairment of cholinergic and dopaminergic pathways due to the action of Lewy bodies formed in the brainstem. Therefore, it would be these structural and functional alterations that would lay the basis for the pattern of functional brain disconnection observed in DLB patients, and would affect the integrity of the ventral occipito-temporal and dorsal occipito-parietal pathways, key in sustaining visuoperceptual and visuospatial functions (Schumacher et al., 2018).

Conclusion

In the context of a neuropsychological evaluation, visuoperceptive and visuospatial disturbances are among those clinical signs that, if you are able to detect and classify, will shed a good stream of light on your working hypotheses. In my case, I take them as one who finds a treasure, although I must admit that I find these clinical signs particularly interesting.

On the other hand, I am not discovering anything new if I say that visuoperceptual and visuospatial functions are not at the top of the popularity list of cognitive functions drawn up by neuropsychologists, with the consequent problem that what is not paid attention to is not investigated, detected or recognized. Yes, yes, we agree, losing memory is hard, we are not going to discuss it here, but losing the ability to recognize and interpret the world before our eyes, being as we are an animal species in which the exploration of the world by visual means predominates, is not a good thing either.

Bibliographical references

Allegri, R. F. (2020). Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing “where” by “what”…. Dementia & Neuropsychologia, 14(3), 237-242.

Auning, E., Rongve, A., Fladby, T., Booij, J., Hortobágyi, T., Siepel, F. J., … & Aarsland, D. (2011). Early and presenting symptoms of dementia with lewy bodies. Dementia and geriatric cognitive disorders, 32(3), 202-208.

Collerton, D., Burn, D., McKeith, I., & O’Brien, J. (2003). Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia. Dementia and geriatric cognitive disorders, 16(4), 229–237.

Donaghy, P. C., & McKeith, I. G. (2014). The clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis. Alzheimer’s research & therapy, 6(4), 46.

Ferman, T. J., Smith, G. E., Boeve, B. F., Graff-Radford, N. R., Lucas, J. A., Knopman, D. S., Petersen, R. C., Ivnik, R. J., Wszolek, Z., Uitti, R., & Dickson, D. W. (2006). Neuropsychological differentiation of dementia with Lewy bodies from normal aging and Alzheimer’s disease. The Clinical neuropsychologist, 20(4), 623–636.

Guidi, M., Paciaroni, L., Paolini, S., De Padova, S., & Scarpino, O. (2006). Differences and similarities in the neuropsychological profile of dementia with Lewy bodies and Alzheimer’s disease in the early stage. Journal of the Neurological Sciences, 248(1-2), 120-123.

Gurnani, A. S., & Gavett, B. E. (2017). The differential effects of Alzheimer’s disease and Lewy Body pathology on cognitive performance: A meta-analysis. Neuropsychology review, 27(1), 1-17.

More references about dementia with Lewy bodies

Hamilton, J. M., Salmon, D. P., Galasko, D., Raman, R., Emond, J., Hansen, L. A., … & Thal, L. J. (2008). Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies. Neuropsychology, 22(6), 729.

Humphreys, G. W., & Riddoch, M. J. (2013). To see but not to see: A case study of visual agnosia. Psychology Press

Kemp, J., Philippi, N., Phillipps, C., Demuynck, C., Albasser, T., Mar-tin-Hunyadi, C., … & Blanc, F. (2017). Cognitive profile in prodromal dementia with Lewy bodies. Alzheimer’s research & therapy, 9(1), 19.

McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J. P., Weintraub, D., … & Kosaka, K. (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89(1), 88-100.

Mak, E., Su, L., Williams, G. B., & T O’Brien, J. (2014). Neuroimaging characteristics of dementia with Lewy bodies. Alzheimer’s research & therapy, 6(2), 18.

Mitolo, M., Hamilton, J. M., Landy, K. M., Hansen, L. A., Galasko, D., Pazzaglia, F., & Salmon, D. P. (2016). Visual perceptual organization ability in autopsy-verified dementia with Lewy bodies and Alzheimer’s disease. Journal of the International Neuropsychological Society, 22(6), 609-619.

Petrova, M., Pavlova, R., Zhelev, Y., Mehrabian, S., Raycheva, M., & Traykov, L. (2016). Investigation of neuropsychological characteristics of very mild and mild dementia with Lewy bodies. Journal of clinical and experimental neuropsychology, 38(3), 354-360.

Schumacher, J., Peraza, L. R., Firbank, M., Thomas, A. J., Kaiser, M., Gallagher, P., … & Taylor, J. P. (2018). Functional connectivity in de-mentia with Lewy bodies: A within‐and between‐network analysis. Hu-man brain mapping, 39(3), 1118-1129.

Tröster, A. I. (2008). Neuropsychological characteristics of dementia with Lewy bodies and Parkinson’s disease with dementia: differentia-tion, early detection, and implications for “mild cognitive impairment” and biomarkers. Neuropsychology review, 18(1), 103-119.

More documentantation about alterations in patients with dementia with Lewy bodies

Oda, H., Yamamoto, Y., & Maeda, K. (2009). Neuropsychological pro-file of dementia with Lewy bodies. Psychogeriatrics, 9(2), 85-90.

Vann Jones, S. A., & O’Brien, J. T. (2014). The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychological medicine, 44(4), 673–683.

Warrington, E. K., & Rudge, P. (1995). A comment on apperceptive agnosia. Brain and cognition, 28(2), 173–179.

Wood, J. S., Firbank, M. J., Mosimann, U. P., Watson, R., Barber, R., Blamire, A. M., & O’Brien, J. T. (2013a). Testing visual perception in dementia with Lewy bodies and Alzheimer disease. The American Jour-nal of Geriatric Psychiatry, 21(6), 501-508.

Wood, J. S., Watson, R., Firbank, M. J., Mosimann, U. P., Barber, R., Blamire, A. M., & O’brien, J. T. (2013b). Longitudinal testing of visual perception in dementia with Lewy bodies and Alzheimer’s disease. International journal of geriatric psychiatry, 28(6), 567-572.

Yokoi, K., Nishio, Y., Uchiyama, M., Shimomura, T., Iizuka, O., & Mori, E. (2014). Hallucinators find meaning in noises: pareidolic illusions in dementia with Lewy bodies. Neuropsychologia, 56, 245–254.

Yousaf, T., Dervenoulas, G., Valkimadi, P. E., & Politis, M. (2019). Neuroimaging in Lewy body dementia. Journal of neurology, 266(1), 1–26.