Parkinson disease-associated cognitive impairment.
Journal
Nature reviews. Disease primers
ISSN: 2056-676X
Titre abrégé: Nat Rev Dis Primers
Pays: England
ID NLM: 101672103
Informations de publication
Date de publication:
01 07 2021
01 07 2021
Historique:
accepted:
27
05
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
26
11
2021
Statut:
epublish
Résumé
Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment.
Identifiants
pubmed: 34210995
doi: 10.1038/s41572-021-00280-3
pii: 10.1038/s41572-021-00280-3
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Commentaires et corrections
Type : ErratumIn
Références
Zaman, V. et al. Cellular and molecular pathophysiology in the progression of Parkinson’s disease. Metab. Brain Dis. 36, 815–827 (2021).
pubmed: 33599945
pmcid: 33599945
Aarsland, D. et al. Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology 56, 730–736 (2001).
pubmed: 11274306
pmcid: 11274306
Leroi, I., McDonald, K., Pantula, H. & Harbishettar, V. Cognitive impairment in Parkinson disease: impact on quality of life, disability, and caregiver burden. J. Geriatr. Psychiatry Neurol. 25, 208–214 (2012).
pubmed: 23172765
pmcid: 23172765
Vossius, C., Larsen, J. P., Janvin, C. & Aarsland, D. The economic impact of cognitive impairment in Parkinson’s disease. Mov. Disord. 26, 1541–1544 (2011).
pubmed: 21538519
pmcid: 21538519
Chandler, J. et al. Characteristics of Parkinson’s disease in patients with and without cognitive impairment. J. Parkinsons Dis. https://doi.org/10.3233/jpd-202190 (2021).
doi: 10.3233/jpd-202190
pubmed: 33720850
pmcid: 33720850
Jessen, F. et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement. 10, 844–852 (2014).
pubmed: 24798886
pmcid: 24798886
Litvan, I. et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov. Disord. 27, 349–356 (2012). MDS PD-MCI criteria making the construct more concrete. These clinical criteria have led to more coherence in the PD field.
pubmed: 22275317
pmcid: 22275317
Emre, M. et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov. Disord. 22, 1689–1707 (2007). quiz 1837.
pubmed: 17542011
pmcid: 17542011
Goetz, C. G., Emre, M. & Dubois, B. Parkinson’s disease dementia: definitions, guidelines, and research perspectives in diagnosis. Ann. Neurol. 64, S81–S92 (2008).
pubmed: 19127578
pmcid: 19127578
Harvey, P. D. Domains of cognition and their assessment. Dialogues Clin. Neurosci. 21, 227–237 (2019).
pubmed: 31749647
pmcid: 31749647
McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89, 88–100 (2017).
pubmed: 28592453
pmcid: 28592453
McKeith, I. G. et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology 94, 743–755 (2020).
pubmed: 32241955
pmcid: 32241955
Postuma, R. B. et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov. Disord. 30, 1591–1601 (2015).
Goldman, J. G. & Weintraub, D. Advances in the treatment of cognitive impairment in Parkinson’s disease. Mov. Disord. 30, 1471–1489 (2015).
pubmed: 26297863
pmcid: 26297863
Seppi, K. et al. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov. Disord. 34, 180–198 (2019).
pubmed: 30653247
pmcid: 30653247
Fengler, S. et al. Cognitive changes in prodromal Parkinson’s disease: a review. Mov. Disord. 32, 1655–1666 (2017).
pubmed: 28980730
pmcid: 28980730
Perez, F. et al. Risk of dementia in an elderly population of Parkinson’s disease patients: a 15-year population-based study. Alzheimers Dement. 8, 463–469 (2012).
pubmed: 22651942
pmcid: 22651942
Aarsland, D., Zaccai, J. & Brayne, C. A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov. Disord. 20, 1255–1263 (2005).
pubmed: 16041803
pmcid: 16041803
Williams-Gray, C. H. et al. The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain 132, 2958–2969 (2009).
pubmed: 19812213
pmcid: 19812213
Williams-Gray, C. H. et al. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J. Neurol. Neurosurg. Psychiatry 84, 1258–1264 (2013).
pubmed: 23781007
pmcid: 23781007
Hely, M. A., Reid, W. G., Adena, M. A., Halliday, G. M. & Morris, J. G. The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov. Disord. 23, 837–844 (2008). The first longitudinal study of a de novo PD cohort demonstrating the high risk of dementia over time.
pubmed: 18307261
pmcid: 18307261
Buter, T. C. et al. Dementia and survival in Parkinson disease: a 12-year population study. Neurology 70, 1017–1022 (2008).
pubmed: 18362281
pmcid: 18362281
Prince, M. et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 9, 63–75 e62 (2013).
pubmed: 23305823
pmcid: 23305823
Aarsland, D. et al. The rate of cognitive decline in Parkinson disease. Arch. Neurol. 61, 1906–1911 (2004).
pubmed: 15596611
pmcid: 15596611
Aarsland, D., Larsen, J. P., Tandberg, E. & Laake, K. Predictors of nursing home placement in Parkinson’s disease: a population-based, prospective study. J. Am. Geriatr. Soc. 48, 938–942 (2000).
pubmed: 10968298
pmcid: 10968298
Aarsland, D. et al. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 75, 1062–1069 (2010).
pubmed: 20855849
pmcid: 20855849
Pedersen, K. F., Larsen, J. P., Tysnes, O. B. & Alves, G. Natural course of mild cognitive impairment in Parkinson disease: a 5-year population-based study. Neurology 88, 767–774 (2017). One of the first studies based on an incidence cohort, reporting the natural course of PD-MCI, diagnosed using standardized criteria over time.
pubmed: 28108638
pmcid: 28108638
Lawson, R. A. et al. Stability of mild cognitive impairment in newly diagnosed Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 88, 648–652 (2017).
pubmed: 28250029
pmcid: 28250029
Domellof, M. E., Ekman, U., Forsgren, L. & Elgh, E. Cognitive function in the early phase of Parkinson’s disease, a five-year follow-up. Acta Neurol. Scand. 132, 79–88 (2015).
pubmed: 25644230
pmcid: 25644230
Weintraub, D. et al. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov. Disord. 30, 919–927 (2015).
pubmed: 25737166
pmcid: 25737166
Roberts, R. & Knopman, D. S. Classification and epidemiology of MCI. Clin. Geriatr. Med. 29, 753–772 (2013).
pubmed: 24094295
pmcid: 24094295
Jones, J. D., Kuhn, T. P. & Szymkowicz, S. M. Reverters from PD-MCI to cognitively intact are at risk for future cognitive impairment: analysis of the PPMI cohort. Parkinsonism Relat. Disord. 47, 3–7 (2018).
pubmed: 29233608
pmcid: 29233608
Wood, K. L. et al. Different PD-MCI criteria and risk of dementia in Parkinson’s disease: 4-year longitudinal study. NPJ Parkinsons Dis. 2, 15027 (2016).
pubmed: 28725690
pmcid: 28725690
Erro, R. et al. Do subjective memory complaints herald the onset of mild cognitive impairment in Parkinson disease. J. Geriatr. Psychiatry Neurol. 27, 276–281 (2014). One of the first studies demonstrating the prognostic impact of subjective memory complaints in PD.
pubmed: 24789732
pmcid: 24789732
Purri, R. et al. Subjective cognitive complaint in Parkinson’s disease patients with normal cognition: canary in the coal mine? Mov. Disord. 35, 1618–1625 (2020).
pubmed: 32520435
pmcid: 32520435
Chua, C. Y. et al. Subjective cognitive complaints in early Parkinson’s disease patients with normal cognition are associated with affective symptoms. Parkinsonism Relat. Disord. 82, 24–28 (2021).
pubmed: 33227684
pmcid: 33227684
Phongpreecha, T. et al. Multivariate prediction of dementia in Parkinson’s disease. NPJ Parkinsons Dis. 6, 20 (2020).
pubmed: 32885039
pmcid: 32885039
Liu, G. et al. Prediction of cognition in Parkinson’s disease with a clinical-genetic score: a longitudinal analysis of nine cohorts. Lancet Neurol. 16, 620–629 (2017).
pubmed: 28629879
pmcid: 28629879
Goetz, C. G. et al. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov. Disord. 19, 1020–1028 (2004).
pubmed: 15372591
pmcid: 15372591
Marinus, J., Zhu, K., Marras, C., Aarsland, D. & van Hilten, J. J. Risk factors for non-motor symptoms in Parkinson’s disease. Lancet Neurol. 17, 559–568 (2018).
pubmed: 29699914
pmcid: 29699914
Williams-Gray, C. H., Foltynie, T., Brayne, C. E., Robbins, T. W. & Barker, R. A. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 130, 1787–1798 (2007).
pubmed: 17535834
pmcid: 17535834
Lee, J. E. et al. Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 85, 7–16 (2014).
pubmed: 23828835
pmcid: 23828835
Chung, S. J. et al. Frontal atrophy as a marker for dementia conversion in Parkinson’s disease with mild cognitive impairment. Hum. Brain Mapp. 40, 3784–3794 (2019).
pubmed: 31090134
pmcid: 31090134
Chung, S. J. et al. Factor analysis-derived cognitive profile predicting early dementia conversion in PD. Neurology 95, e1650–e1659 (2020).
pubmed: 32651296
pmcid: 32651296
Livingston, G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396, 413–446 (2020).
pubmed: 32738937
pmcid: 32738937
Chahine, L. M. et al. Cognition in individuals at risk for Parkinson’s: Parkinson associated risk syndrome (PARS) study findings. Mov. Disord. 31, 86–94 (2016).
pubmed: 26293177
pmcid: 26293177
Gagnon, J. F. et al. Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson’s disease. Ann. Neurol. 66, 39–47 (2009).
pubmed: 19670440
pmcid: 19670440
Gagnon, J. F., Bertrand, J. A. & Genier Marchand, D. Cognition in rapid eye movement sleep behavior disorder. Front. Neurol. 3, 82 (2012).
pubmed: 22629254
pmcid: 22629254
Heinzel, S. et al. Update of the MDS research criteria for prodromal Parkinson’s disease. Mov. Disord. 34, 1464–1470 (2019).
pubmed: 31412427
pmcid: 31412427
Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Prim. 3, 17013 (2017).
pubmed: 28332488
pmcid: 28332488
Bridi, J. C. & Hirth, F. Mechanisms of α-synuclein induced synaptopathy in Parkinson’s disease. Front. Neurosci. 12, 80 (2018).
pubmed: 29515354
pmcid: 29515354
Sasikumar, S. & Strafella, A. P. Imaging mild cognitive impairment and dementia in Parkinson’s disease. Front. Neurol. 11, 47 (2020).
pubmed: 32082250
pmcid: 32082250
Ranganath, A. & Jacob, S. N. Doping the mind: dopaminergic modulation of prefrontal cortical cognition. Neuroscientist 22, 593–603 (2016).
pubmed: 26338491
pmcid: 26338491
Westbrook, A. et al. Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work. Science 367, 1362–1366 (2020).
pubmed: 7430502
pmcid: 7430502
Keren, N. I. et al. Histologic validation of locus coeruleus MRI contrast in post-mortem tissue. Neuroimage 113, 235–245 (2015).
pubmed: 25791783
pmcid: 25791783
Borodovitsyna, O., Flamini, M. & Chandler, D. Noradrenergic modulation of cognition in health and disease. Neural Plast. 2017, 6031478 (2017).
pubmed: 28596922
pmcid: 28596922
Li, Y. et al. Mild cognitive impairment in de novo Parkinson’s disease: a neuromelanin MRI study in locus coeruleus. Mov. Disord. 34, 884–892 (2019).
pubmed: 30938892
pmcid: 30938892
Ehrminger, M. et al. The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder. Brain 139, 1180–1188 (2016).
pubmed: 26920675
pmcid: 26920675
Sommerauer, M. et al. Evaluation of the noradrenergic system in Parkinson’s disease: an
pubmed: 29272343
pmcid: 29272343
Longardner, K., Bayram, E. & Litvan, I. Orthostatic hypotension is associated with cognitive decline in Parkinson disease. Front. Neurol. 11, 897 (2020).
pubmed: 32982926
pmcid: 32982926
McDonald, C., Newton, J. L. & Burn, D. J. Orthostatic hypotension and cognitive impairment in Parkinson’s disease: causation or association? Mov. Disord. 31, 937–946 (2016).
pubmed: 27091624
pmcid: 27091624
Sinn, D. I. & Gibbons, C. H. Pathophysiology and treatment of orthostatic hypotension in parkinsonian disorders. Curr. Treat. Options Neurol. 18, 28 (2016).
pubmed: 27138287
pmcid: 27138287
Zhan, Y., Raza, M. U., Yuan, L. & Zhu, M. Y. Critical role of oxidatively damaged DNA in selective noradrenergic vulnerability. Neuroscience 422, 184–201 (2019).
pubmed: 31698021
pmcid: 31698021
van der Zee, S. et al. Monoaminergic markers across the cognitive spectrum of Lewy body disease. J. Parkinsons Dis. 8, 71–84 (2018).
pubmed: 29480224
pmcid: 29480224
Buddhala, C. et al. Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease. Ann. Clin. Transl. Neurol. 2, 949–959 (2015).
pubmed: 26478895
pmcid: 26478895
Betts, M. J. et al. Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. Brain 142, 2558–2571 (2019).
pubmed: 31327002
pmcid: 31327002
Ballinger, E. C., Ananth, M., Talmage, D. A. & Role, L. W. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron 91, 1199–1218 (2016).
pubmed: 27657448
pmcid: 27657448
Pillet, L. E. et al. Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution. Transl. Psychiatry 10, 213 (2020).
pubmed: 32620743
pmcid: 32620743
Schulz, J., Pagano, G., Fernandez Bonfante, J. A., Wilson, H. & Politis, M. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson’s disease. Brain 141, 1501–1516 (2018).
pubmed: 29701787
pmcid: 29701787
Bohnen, N. I. et al. Frequency of cholinergic and caudate nucleus dopaminergic deficits across the predemented cognitive spectrum of Parkinson disease and evidence of interaction effects. JAMA Neurol. 72, 194–200 (2015).
pubmed: 25506674
pmcid: 25506674
Pereira, J. B. et al. Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson’s disease. Neurobiol. Dis. 139, 104831 (2020).
pubmed: 32145376
pmcid: 32145376
Ray, N. J. et al. In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease. Brain 141, 165–176 (2018).
pubmed: 29228203
pmcid: 29228203
Alexandris, A. S. et al. Cholinergic deficits and galaninergic hyperinnervation of the nucleus basalis of Meynert in Alzheimer’s disease and Lewy body disorders. Neuropathol. Appl. Neurobiol. 46, 264–278 (2020).
pubmed: 31454423
pmcid: 31454423
Mattila, P. M. et al. Choline acetytransferase activity and striatal dopamine receptors in Parkinson’s disease in relation to cognitive impairment. Acta Neuropathol. 102, 160–166 (2001).
pubmed: 11563631
pmcid: 11563631
Gaykema, R. P. & Zaborszky, L. Direct catecholaminergic-cholinergic interactions in the basal forebrain. II. Substantia nigra-ventral tegmental area projections to cholinergic neurons. J. Comp. Neurol. 374, 555–577 (1996).
pubmed: 8910735
pmcid: 8910735
Gargouri, F. et al. Multimodal magnetic resonance imaging investigation of basal forebrain damage and cognitive deficits in Parkinson’s disease. Mov. Disord. 34, 516–525 (2019).
pubmed: 30536444
pmcid: 30536444
Hall, H. et al. Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson’s disease. Brain 137, 2493–2508 (2014).
pubmed: 25062696
pmcid: 25062696
Liu, A. K. L. et al. Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson’s disease with cognitive decline. Acta Neuropathol. Commun. 7, 61 (2019).
pubmed: 31023342
pmcid: 31023342
Nicastro, N., Garibotto, V. & Burkhard, P. R. Extrastriatal
pubmed: 32416724
pmcid: 32416724
Pagano, G., Niccolini, F., Fusar-Poli, P. & Politis, M. Serotonin transporter in Parkinson’s disease: a meta-analysis of positron emission tomography studies. Ann. Neurol. 81, 171–180 (2017).
pubmed: 28019672
pmcid: 28019672
Qamhawi, Z. et al. Clinical correlates of raphe serotonergic dysfunction in early Parkinson’s disease. Brain 138, 2964–2973 (2015).
pubmed: 26209314
pmcid: 26209314
Maillet, A. et al. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson’s disease. Brain 139, 2486–2502 (2016).
pubmed: 27538418
pmcid: 27538418
Kotagal, V., Spino, C., Bohnen, N. I., Koeppe, R. & Albin, R. L. Serotonin, beta-amyloid, and cognition in Parkinson disease. Ann. Neurol. 83, 994–1002 (2018).
pubmed: 29665066
pmcid: 29665066
Smith, C. R. et al. Cognitive impairment in Parkinson’s disease is multifactorial: a neuropsychological study. Acta Neurol. Scand. 141, 500–508 (2020).
pubmed: 32002988
pmcid: 32002988
Amin, J. et al. Neuroinflammation in dementia with Lewy bodies: a human post-mortem study. Transl. Psychiatry 10, 267 (2020).
pubmed: 32747635
pmcid: 32747635
Smith, C. et al. Neuropathology of dementia in patients with Parkinson’s disease: a systematic review of autopsy studies. J. Neurol. Neurosurg. Psychiatry 90, 1234–1243 (2019). Assessment of neuropathology underlying dementia in >2,000 end-stage autopsy cases showing that significant α-synuclein pathology is the main substrate, although coexisting Alzheimer pathologies are common (about one-third of cases) and independently contribute to dementia in PD.
pubmed: 31444276
pmcid: 31444276
Dauvilliers, Y. et al. REM sleep behaviour disorder. Nat. Rev. Dis. Prim. 4, 19 (2018).
pubmed: 30166532
pmcid: 30166532
Jia, X. et al. Entorhinal cortex atrophy in early, drug-naive Parkinson’s disease with mild cognitive impairment. Aging Dis. 10, 1221–1232 (2019).
pubmed: 31788334
pmcid: 31788334
Devanand, D. P. et al. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology 68, 828–836 (2007).
pubmed: 17353470
pmcid: 17353470
Harding, A. J. & Halliday, G. M. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol. 102, 355–363 (2001).
pubmed: 11603811
pmcid: 11603811
Dickson, D. W. et al. Neuropathological assessment of Parkinson’s disease: refining the diagnostic criteria. Lancet Neurol. 8, 1150–1157 (2009).
pubmed: 19909913
pmcid: 19909913
Yu, L. et al. Common age-related neuropathologies and yearly variability in cognition. Ann. Clin. Transl. Neurol. 6, 2140–2149 (2019).
pubmed: 31568713
pmcid: 31568713
Schaser, A. J. et al. Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders. Sci. Rep. 9, 10919 (2019).
pubmed: 31358782
pmcid: 31358782
Power, J. H., Barnes, O. L. & Chegini, F. Lewy bodies and the mechanisms of neuronal cell death in Parkinson’s disease and dementia with lewy bodies. Brain Pathol. 27, 3–12 (2017).
pubmed: 26667592
pmcid: 26667592
Tagliafierro, L. et al. Genetic analysis of alpha-synuclein 3’ untranslated region and its corresponding microRNAs in relation to Parkinson’s disease compared to dementia with Lewy bodies. Alzheimers Dement. 13, 1237–1250 (2017).
pubmed: 28431219
pmcid: 28431219
Guella, I. et al. alpha-synuclein genetic variability: a biomarker for dementia in Parkinson disease. Ann. Neurol. 79, 991–999 (2016).
pubmed: 27091628
pmcid: 27091628
Gamez-Valero, A. et al. INDEL length and haplotypes in the beta-synuclein gene: a key to differentiate dementia with Lewy bodies? J. Alzheimers Dis. 65, 207–219 (2018).
pubmed: 30040713
pmcid: 30040713
Tseng, E. et al. The landscape of SNCA transcripts across synucleinopathies: new insights from long reads sequencing analysis. Front. Genet. 10, 584 (2019).
pubmed: 31338105
pmcid: 31338105
Van der Perren, A. et al. The structural differences between patient-derived alpha-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies. Acta Neuropathol. 139, 977–1000 (2020). Using homogenized brain proteins from patients dichotomised for different clinical forms of α-synucleinopathies, the authors made pure amplified α-synuclein and showed significant differences in the ‘strains’ of α-synuclein in each of the major α-synucleinopathies. Signature ‘strains’ of α-synuclein may be diagnostic and also better targeted therapeutically.
pubmed: 32356200
pmcid: 32356200
Candelise, N. et al. Seeding variability of different alpha synuclein strains in synucleinopathies. Ann. Neurol. 85, 691–703 (2019).
pubmed: 30805957
pmcid: 30805957
Petrou, M. et al. Amyloid deposition in Parkinson’s disease and cognitive impairment: a systematic review. Mov. Disord. 30, 928–935 (2015).
pubmed: 25879534
pmcid: 25879534
Melzer, T. R. et al. Beta amyloid deposition is not associated with cognitive impairment in Parkinson’s disease. Front. Neurol. 10, 391 (2019).
pubmed: 31105633
pmcid: 31105633
Winer, J. R. et al. Associations between Tau, beta-amyloid, and cognition in Parkinson disease. JAMA Neurol. 75, 227–235 (2018). Assessment of AD protein deposition associated with cognitive deficits in PD showing that PD-MCI is not related to the measurable deposition of these proteins, indicating that such protein deposition occurs with progression to dementia in a proportion of patients with PD.
pubmed: 29228071
pmcid: 29228071
Reimand, J. et al. Association of amyloid-beta CSF/PET discordance and tau load 5 years later. Neurology 95, e2648–e2657 (2020).
pubmed: 32913020
pmcid: 32913020
Toledo, J. B. et al. Pathological alpha-synuclein distribution in subjects with coincident Alzheimer’s and Lewy body pathology. Acta Neuropathol. 131, 393–409 (2016).
pubmed: 26721587
pmcid: 26721587
Irwin, D. J. et al. Neuropathologic substrates of Parkinson disease dementia. Ann. Neurol. 72, 587–598 (2012).
pubmed: 23037886
pmcid: 23037886
Howard, E. et al. Cognitive profile and markers of AD-type pathology in patients with Lewy body dementias. Neurology 96, e1855–e1864 (2021).
pubmed: 33593865
pmcid: 33593865
Tan, M. M. X. et al. Genome-wide association studies of cognitive and motor progression in Parkinson’s disease. Mov. Disord. 36, 424–433 (2021).
pubmed: 33111402
pmcid: 33111402
Iwaki, H. et al. Genomewide association study of Parkinson’s disease clinical biomarkers in 12 longitudinal patients’ cohorts. Mov. Disord. 34, 1839–1850 (2019).
pubmed: 31505070
pmcid: 31505070
D’Souza, T. & Rajkumar, A. P. Systematic review of genetic variants associated with cognitive impairment and depressive symptoms in Parkinson’s disease. Acta Neuropsychiatr. 32, 10–22 (2020).
pubmed: 31292011
pmcid: 31292011
Hopfner, F. et al. Rare variants in specific lysosomal genes are associated with Parkinson’s disease. Mov. Disord. 35, 1245–1248 (2020).
pubmed: 32267580
pmcid: 32267580
Chia, R. et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat. Genet. 53, 294–303 (2021).
pubmed: 33589841
pmcid: 33589841
Henderson, M. X. et al. Glucocerebrosidase activity modulates neuronal susceptibility to pathological α-synuclein insult. Neuron 105, 822–836.e7 (2020).
Jiang, Z. et al. Characterization of a pathogenic variant in GBA for Parkinson’s disease with mild cognitive impairment patients. Mol. Brain 13, 102 (2020).
pubmed: 32641146
pmcid: 32641146
Roussotte, F. F. et al. Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion. Alzheimers Dement. 11, 1153–1162 (2015).
pubmed: 25496873
pmcid: 25496873
Martelle, S. E. et al. Dopamine pathway gene variants may modulate cognitive performance in the DHS - Mind Study. Brain Behav. 6, e00446 (2016).
pubmed: 27066308
pmcid: 27066308
Caspell-Garcia, C. et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One 12, e0175674 (2017).
pubmed: 28520803
pmcid: 28520803
Miranda, G. G., Rodrigue, K. M. & Kennedy, K. M. Frontoparietal cortical thickness mediates the effect of COMT Val(158)Met polymorphism on age-associated executive function. Neurobiol. Aging 73, 104–114 (2019).
pubmed: 30342271
pmcid: 30342271
Backstrom, D. et al. Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson’s disease. Acta Neurol. Scand. 137, 91–98 (2018).
pubmed: 28869277
pmcid: 28869277
Skorvanek, M. et al. Global scales for cognitive screening in Parkinson’s disease: critique and recommendations. Mov. Disord. 33, 208–218 (2018).
pubmed: 29168899
pmcid: 29168899
Nasreddine, Z. S. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695–699 (2005).
pubmed: 15817019
pmcid: 15817019
Mattis, S. Dementia Rating Scale: Professional Manual (Psychological Assessment Resources Incorporated, 1988).
Pagonabarraga, J. et al. Parkinson’s disease-cognitive rating scale: a new cognitive scale specific for Parkinson’s disease. Mov. Disord. 23, 998–1005 (2008).
pubmed: 18381647
pmcid: 18381647
Caslake, R. et al. The mini-mental Parkinson’s (MMP) as a cognitive screening tool in people with Parkinson’s disease. Curr. Aging Sci. 6, 273–279 (2013).
pubmed: 23773030
pmcid: 23773030
Marinus, J. et al. Assessment of cognition in Parkinson’s disease. Neurology 61, 1222 (2003).
pubmed: 14610124
pmcid: 14610124
Hoops, S. et al. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 73, 1738–1745 (2009).
pubmed: 19933974
pmcid: 19933974
Marras, C. et al. Measuring mild cognitive impairment in patients with Parkinson’s disease. Mov. Disord. 28, 626–633 (2013).
pubmed: 23520128
pmcid: 23520128
Hoogland, J. et al. Detecting mild cognitive deficits in Parkinson’s disease: comparison of neuropsychological tests. Mov. Disord. 33, 1750–1759 (2018).
pubmed: 30216541
pmcid: 30216541
Chaudhuri, K. R. et al. The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov. Disord. 22, 1901–1911 (2007).
pubmed: 17674410
pmcid: 17674410
Chaudhuri, K. R. et al. The Movement Disorder Society Nonmotor Rating Scale: initial validation study. Mov. Disord. 35, 116–133 (2020).
pubmed: 31571279
pmcid: 31571279
Chaudhuri, K. R. et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov. Disord. 21, 916–923 (2006).
pubmed: 16547944
pmcid: 16547944
Kulisevsky, J. et al. Measuring functional impact of cognitive impairment: validation of the Parkinson’s disease cognitive functional rating scale. Parkinsonism Relat. Disord. 19, 812–817 (2013).
pubmed: 23773412
pmcid: 23773412
Brennan, L. et al. The Penn Parkinson’s Daily Activities Questionnaire-15: psychometric properties of a brief assessment of cognitive instrumental activities of daily living in Parkinson’s disease. Parkinsonism Relat. Disord. 25, 21–26 (2016).
pubmed: 26923524
pmcid: 26923524
Hoogland, J. et al. Risk of Parkinson’s disease dementia related to level I MDS PD-MCI. Mov. Disord. 34, 430–435 (2019). Validation of the level I and level II PD-MCI criteria by showing their predictive value for PDD in a large combination of cohorts.
pubmed: 30653248
pmcid: 30653248
Hoogland, J. et al. Mild cognitive impairment as a risk factor for Parkinson’s disease dementia. Mov. Disord. 32, 1056–1065 (2017).
pubmed: 28605056
pmcid: 28605056
Saredakis, D., Collins-Praino, L. E., Gutteridge, D. S., Stephan, B. C. M. & Keage, H. A. D. Conversion to MCI and dementia in Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat. Disord. 65, 20–31 (2019).
pubmed: 31109727
pmcid: 31109727
Baiano, C., Barone, P., Trojano, L. & Santangelo, G. Prevalence and clinical aspects of mild cognitive impairment in Parkinson’s disease: a meta-analysis. Mov. Disord. 35, 45–54 (2020). Meta-analysis of the prevalence rate of PD-MCI according to the MDS clinical criteria. Furthermore, an exploration of the differences between patients with and without PD-MCI in demographic, clinical and neuropsychiatric features.
pubmed: 31743500
pmcid: 31743500
Rosen, W. G., Mohs, R. C. & Davis, K. L. A new rating scale for Alzheimer’s disease. Am. J. Psychiatry 141, 1356–1364 (1984).
pubmed: 6496779
pmcid: 6496779
Galasko, D. et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis. Assoc. Disord. 11 (Suppl. 2), S33–S39 (1997).
pubmed: 9236950
pmcid: 9236950
Schneider, L. S. et al. Validity and reliability of the Alzheimer’s disease cooperative study-clinical global impression of change. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis. Assoc. Disord. 11 (Suppl. 2), S22–S32 (1997).
pubmed: 9236949
pmcid: 9236949
Arvanitakis, Z., Shah, R. C. & Bennett, D. A. Diagnosis and management of dementia: review. JAMA 322, 1589–1599 (2019).
pubmed: 31638686
pmcid: 31638686
Burton, E. J., McKeith, I. G., Burn, D. J., Williams, E. D. & O’Brien, J. T. Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain 127, 791–800 (2004).
pubmed: 14749292
pmcid: 14749292
Hwang, K. S. et al. Mapping cortical atrophy in Parkinson’s disease patients with dementia. J. Parkinsons Dis. 3, 69–76 (2013).
pubmed: 23938313
pmcid: 23938313
Dubois, B. et al. Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov. Disord. 22, 2314–2324 (2007).
pubmed: 18098298
pmcid: 18098298
Smirnov, D. S. et al. Cognitive decline profiles differ in Parkinson disease dementia and dementia with Lewy bodies. Neurology 94, e2076–e2087 (2020).
pubmed: 32332125
pmcid: 32332125
Petrova, M., Mehrabian-Spasova, S., Aarsland, D., Raycheva, M. & Traykov, L. Clinical and neuropsychological differences between mild Parkinson’s disease dementia and dementia with Lewy bodies. Dement. Geriatr. Cogn. Disord. Extra 5, 212–220 (2015).
Owens, A. P. et al. Implementing remote memory clinics to enhance clinical care during and after COVID-19. Front. Psychiatry 11, 579934 (2020).
pubmed: 33061927
pmcid: 33061927
Brooker, H. et al. FLAME: a computerized neuropsychological composite for trials in early dementia. Alzheimers Dement. 12, e12098 (2020).
Owens, A. P. et al. Selecting remote measurement technologies to optimize assessment of function in early Alzheimer’s disease: a case study. Front. Psychiatry 11, 1163 (2020).
van den Berg, E., Ruis, C., Biessels, G. J., Kappelle, L. J. & van Zandvoort, M. J. The Telephone Interview for Cognitive Status (Modified): relation with a comprehensive neuropsychological assessment. J. Clin. Exp. Neuropsychol. 34, 598–605 (2012).
pubmed: 22384819
pmcid: 22384819
Marra, D. E., Hamlet, K. M., Bauer, R. M. & Bowers, D. Validity of teleneuropsychology for older adults in response to COVID-19: A systematic and critical review. Clin. Neuropsychol. 34, 1411–1452 (2020).
pubmed: 32519594
pmcid: 32519594
Phillips, N. A., Chertkow, H., Pichora-Fuller, M. K. & Wittich, W. Special issues on using the Montreal Cognitive Assessment for telemedicine Assessment during COVID-19. J. Am. Geriatrics Soc. 68, 942–944 (2020).
Schrag, A., Siddiqui, U. F., Anastasiou, Z., Weintraub, D. & Schott, J. M. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol. 16, 66–75 (2017).
pubmed: 27866858
pmcid: 27866858
Weintraub, D. et al. Alzheimer’s disease pattern of brain atrophy predicts cognitive decline in Parkinson’s disease. Brain 135, 170–180 (2012).
pubmed: 22108576
pmcid: 22108576
Huang, C. et al. Metabolic brain networks associated with cognitive function in Parkinson’s disease. Neuroimage 34, 714–723 (2007).
pubmed: 17113310
pmcid: 17113310
Lanskey, J. H. et al. Can neuroimaging predict dementia in Parkinson’s disease? Brain 141, 2545–2560 (2018).
pubmed: 30137209
pmcid: 30137209
Zhang, Y., Wu, I. W., Tosun, D., Foster, E. & Schuff, N. Progression of regional microstructural degeneration in Parkinson’s disease: a multicenter diffusion tensor imaging study. PLoS One 11, e0165540 (2016).
pubmed: 27798653
pmcid: 27798653
Siderowf, A. et al. CSF amyloid {beta} 1-42 predicts cognitive decline in Parkinson disease. Neurology 75, 1055–1061 (2010).
pubmed: 20720189
pmcid: 20720189
Johar, I., Mollenhauer, B. & Aarsland, D. Cerebrospinal fluid biomarkers of cognitive decline in Parkinson’s disease. Int. Rev. Neurobiol. 132, 275–294 (2017).
pubmed: 28554411
pmcid: 28554411
Yousaf, T., Pagano, G., Niccolini, F. & Politis, M. Predicting cognitive decline with non-clinical markers in Parkinson’s disease (PRECODE-2). J. Neurol. 266, 1203–1210 (2019).
pubmed: 30820739
pmcid: 30820739
Hansen, A. K. et al. Tau tangles in Parkinson’s disease: a 2-year follow-up flortaucipir PET study. J. Parkinsons Dis. 10, 161–171 (2020).
pubmed: 31815700
pmcid: 31815700
Lin, C. H. & Wu, R. M. Biomarkers of cognitive decline in Parkinson’s disease. Parkinsonism Relat. Disord. 21, 431–443 (2015).
pubmed: 25737398
pmcid: 25737398
Mavroudis, I., Petridis, F., Chatzikonstantinou, S. & Kazis, D. Alpha-synuclein levels in the differential diagnosis of Lewy bodies dementia and other neurodegenerative disorders: a meta-analysis. Alzheimer Dis. Assoc. Disord. 34, 220–224 (2020).
pubmed: 32341240
pmcid: 32341240
Paciotti, S., Bellomo, G., Gatticchi, L. & Parnetti, L. Are we ready for detecting α-synuclein prone to aggregation in patients? The case of “protein-misfolding cyclic amplification” and “real-time quaking-induced conversion” as diagnostic tools. Front. Neurol. 9, 415 (2018).
pubmed: 29928254
pmcid: 29928254
Massa, F. et al. Utility of quantitative EEG in early Lewy body disease. Parkinsonism Relat. Disord. 75, 70–75 (2020).
pubmed: 32480310
pmcid: 32480310
Betrouni, N. et al. Electroencephalography-based machine learning for cognitive profiling in Parkinson’s disease: preliminary results. Mov. Disord. 34, 210–217 (2019).
pubmed: 30345602
pmcid: 30345602
Bonanni, L. et al. EEG comparisons in early Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease with dementia patients with a 2-year follow-up. Brain 131, 690–705 (2008).
pubmed: 18202105
pmcid: 18202105
Klassen, B. T. et al. Quantitative EEG as a predictive biomarker for Parkinson disease dementia. Neurology 77, 118–124 (2011).
pubmed: 21633128
pmcid: 21633128
Emre, M. et al. Rivastigmine for dementia associated with Parkinson’s disease. N. Engl. J. Med. 351, 2509–2518 (2004).
pubmed: 15590953
pmcid: 15590953
Mamikonyan, E., Xie, S. X., Melvin, E. & Weintraub, D. Rivastigmine for mild cognitive impairment in Parkinson disease: a placebo-controlled study. Mov. Disord. 30, 912–918 (2015).
pubmed: 25914281
pmcid: 25914281
Emre, M. et al. Long-term safety of rivastigmine in Parkinson disease dementia: an open-label, randomized study. Clin. Neuropharmacol. 37, 9–16 (2014).
pubmed: 24434526
pmcid: 24434526
Dubois, B. et al. Donepezil in Parkinson’s disease dementia: a randomized, double-blind efficacy and safety study. Mov. Disord. 27, 1230–1238 (2012).
pubmed: 22915447
pmcid: 22915447
Aarsland, D. et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 8, 613–618 (2009).
pubmed: 19520613
pmcid: 19520613
Emre, M. et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomized, double-blind, placebo-controlled trial. Lancet Neurol. 9, 969–977 (2010).
pubmed: 20729148
pmcid: 20729148
Wang, H. F. et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J. Neurol. Neurosurg. Psychiatry 86, 135–143 (2015).
pubmed: 24828899
pmcid: 24828899
Taylor, J. P. et al. New evidence on the management of Lewy body dementia. Lancet Neurol. 19, 157–169 (2020). Review addressing existing gaps in the management of Lewy body dementia (DLB and PDD) and covering the current management of key domains of cognitive impairment, neuropsychiatric symptoms as well as motor and other non-motor symptoms.
pubmed: 31519472
pmcid: 31519472
Litvan, I., Kieburtz, K., Tröster, A. I. & Aarsland, D. Strengths and challenges in conducting clinical trials in Parkinson’s disease mild cognitive impairment. Mov. Disord. 33, 520–527 (2018).
pubmed: 29573469
pmcid: 29573469
Weintraub, D. et al. Rasagiline for mild cognitive impairment in Parkinson’s disease: a placebo-controlled trial. Mov. Disord. 31, 709–714 (2016).
pubmed: 27030249
pmcid: 27030249
Sawada, H. et al. Early use of donepezil against psychosis and cognitive decline in Parkinson’s disease: a randomised controlled trial for 2 years. J. Neurol. Neurosurg. Psychiatry 89, 1332–1340 (2018).
pubmed: 30076270
pmcid: 30076270
Weintraub, D. et al. Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson’s disease. Neurology 75, 448–455 (2010).
pubmed: 20679638
pmcid: 20679638
Kehagia, A. et al. Targeting impulsivity in Parkinson’s disease using atomoxetine. Brain 137, 1986–1997 (2014).
pubmed: 24893708
pmcid: 24893708
Hinson, V. K., Delambo, A., Elm, J. & Turner, T. A randomized clinical trial of atomoxetine for mild cognitive impairment in Parkinson’s disease. Mov. Disord. Clin. Pract. 4, 416–423 (2017).
pubmed: 30363371
pmcid: 30363371
Biundo, R., Weis, L., Fiorenzato, E. & Antonini, A. Cognitive rehabilitation in Parkinson’s disease: is it feasible? Arch. Clin. Neuropsychol. 32, 840–860 (2017).
pubmed: 28961738
pmcid: 28961738
Lawrence, B. J., Gasson, N., Bucks, R. S., Troeung, L. & Loftus, A. M. Cognitive training and noninvasive brain stimulation for cognition in Parkinson’s disease: a meta-analysis. Neurorehabil Neural Repair. 31, 597–608 (2017).
pubmed: 28583011
pmcid: 28583011
Leung, I. H. et al. Cognitive training in Parkinson disease: a systematic review and meta-analysis. Neurology 85, 1843–1851 (2015).
pubmed: 26519540
pmcid: 26519540
Orgeta, V. et al. Cognitive training interventions for dementia and mild cognitive impairment in Parkinson’s disease. Cochrane Database Syst. Rev. 2, CD011961 (2020). Systematic review investigating whether cognitive training improves cognition in people with PDD and PD-MCI or other clearly defined forms of cognitive impairment in people with PD.
pubmed: 32101639
pmcid: 32101639
Lauze, M., Daneault, J. F. & Duval, C. The effects of physical activity in Parkinson’s disease: a review. J. Parkinsons Dis. 6, 685–698 (2016).
pubmed: 27567884
pmcid: 27567884
da Silva, F. C. et al. Effects of physical exercise programs on cognitive function in Parkinson’s disease patients: a systematic review of randomized controlled trials of the last 10 years. PLoS One 13, e0193113 (2018). Systematic review aiming to determine the effects of physical exercise programmes on cognitive function in patients with PD.
pubmed: 29486000
pmcid: 29486000
Dinkelbach, L., Brambilla, M., Manenti, R. & Brem, A. K. Non-invasive brain stimulation in Parkinson’s disease: exploiting crossroads of cognition and mood. Neurosci. Biobehav. Rev. 75, 407–418 (2017).
pubmed: 28119070
pmcid: 28119070
Nousia, A. et al. The beneficial effects of computer-based cognitive training in Parkinson’s disease: a systematic review. Arch. Clin. Neuropsychol. 35, 434–447 (2020).
pubmed: 31942917
pmcid: 31942917
Stuckenschneider, T. et al. The effect of different exercise modes on domain-specific cognitive function in patients suffering from Parkinson’s disease: a systematic review of randomized controlled trials. J. Parkinsons Dis. 9, 73–95 (2019).
pubmed: 30741688
pmcid: 30741688
Lefaucheur, J. P. et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin. Neurophysiol. 128, 56–92 (2017).
pubmed: 27866120
pmcid: 27866120
Auvichayapat, P. & Auvichayapat, N. Basic principle of transcranial magnetic stimulation. J. Med. Assoc. Thai 92, 1560–1566 (2009).
pubmed: 19938752
pmcid: 19938752
Gratwicke, J. et al. Bilateral deep brain stimulation of the nucleus basalis of Meynert for Parkinson disease dementia: a randomized clinical trial. JAMA Neurol. 75, 169–178 (2018).
pubmed: 29255885
pmcid: 29255885
PD Med Collaborative Group, et al.Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet 384, 1196–1205 (2014).
Verschuur, C. V. M. et al. Randomized delayed-start trial of levodopa in Parkinson’s disease. N. Engl. J. Med. 380, 315–324 (2019).
pubmed: 30673543
pmcid: 30673543
Abraham, D. S. et al. Frequency of and risk factors for potentially inappropriate medication use in Parkinson’s disease. Age Ageing 49, 786–792 (2020).
pubmed: 32255485
pmcid: 32255485
Mantri, S. et al. Patterns of dementia treatment and frank prescribing errors in older adults with Parkinson disease. JAMA Neurol. 76, 41–49 (2019).
pubmed: 30285047
pmcid: 30285047
Ehrt, U., Broich, K., Larsen, J., Ballard, C. & Aarsland, D. Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: a cohort study. J. Neurol. Neurosurg. Psychiatry 81, 160–165 (2010).
pubmed: 19770163
pmcid: 19770163
Witt, K. et al. Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson’s disease: results from a randomized trial. Brain 136, 2109–2119 (2013).
pubmed: 23801735
pmcid: 23801735
Frankemolle, A. et al. Reversing cognitive-motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming. Brain 133, 746–761 (2010).
pubmed: 20061324
pmcid: 20061324
Schuepbach, W. M. et al. Neurostimulation for Parkinson’s disease with early motor complications. N. Engl. J. Med. 368, 610–622 (2013).
pubmed: 23406026
pmcid: 23406026
Trenkwalder, C. et al. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease — clinical practice recommendations. Parkinsonism Relat. Disord. 21, 1023–1030 (2015).
pubmed: 26189414
pmcid: 26189414
Timpka, J., Nitu, B., Datieva, V., Odin, P. & Antonini, A. Device-aided treatment strategies in advanced Parkinson’s disease. Int. Rev. Neurobiol. 132, 453–474 (2017).
pubmed: 28554418
pmcid: 28554418
Chahine, L. M. et al. The most bothersome aspects of off periods reported by individuals with Parkinson’s disease. Mov. Disord. Clin. Pract. 7, 284–292 (2020).
pubmed: 32258226
pmcid: 32258226
Witjas, T. et al. Nonmotor fluctuations in Parkinson’s disease: frequent and disabling. Neurology 59, 408–413 (2002).
pubmed: 12177375
pmcid: 12177375
Chahine, L. M. et al. Modifiable vascular risk factors, white matter disease and cognition in early Parkinson’s disease. Eur. J. Neurol. 26, 246–e18 (2019).
pubmed: 30169897
pmcid: 30169897
Mollenhauer, B. et al. Baseline predictors for progression 4 years after Parkinson’s disease diagnosis in the De Novo Parkinson Cohort (DeNoPa). Mov. Disord. 34, 67–77 (2019).
pubmed: 30468694
pmcid: 30468694
Knox, M. G. et al. Neuropathological findings in Parkinson’s disease with mild cognitive impairment. Mov. Disord. 35, 845–850 (2020).
pubmed: 32034933
pmcid: 32034933
Centi, J. et al. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology 88, 17–24 (2017).
pubmed: 27903817
pmcid: 27903817
Harmell, A. L. et al. Obstructive sleep apnea and cognition in Parkinson’s disease. Sleep. Med. 21, 28–34 (2016).
pubmed: 27448468
pmcid: 27448468
Kaminska, M. et al. Change in cognition and other non-motor symptoms with obstructive sleep apnea treatment in Parkinson disease. J. Clin. Sleep. Med. 14, 819–828 (2018).
pubmed: 29734988
pmcid: 29734988
Jester, D. J., Lee, S., Molinari, V. & Volicer, L. Cognitive deficits in Parkinson’s disease with excessive daytime sleepiness: a systematic review. Aging Ment. Health 24, 1769–1780 (2020).
pubmed: 31478402
pmcid: 31478402
Li, Z. et al. The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson’s disease. Eur. Neurol. 73, 205–211 (2015).
pubmed: 25792086
pmcid: 25792086
Varela-López, A., Giampieri, F., Battino, M. & Quiles, J. L. Coenzyme Q and its role in the dietary therapy against aging. Molecules 21, 373 (2016).
pubmed: 26999099
pmcid: 26999099
Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T. & Widmer, H. R. Functions and effects of creatine in the central nervous system. Brain Res. Bull. 76, 329–343 (2008).
pubmed: 18502307
pmcid: 18502307
Mo, J. J. et al. The effectiveness of creatine treatment for Parkinson’s disease: an updated meta-analysis of randomized controlled trials. BMC Neurol. 17, 105 (2017).
pubmed: 28577542
pmcid: 28577542
Parkinson Study Group QE3 Investigators et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 71, 543–552 (2014).
Svenningsson, P. et al. A phase 2a trial investigating the safety and tolerability of the novel cortical enhancer IRL752 in Parkinson’s disease dementia. Mov. Disord. 35, 1046–1054 (2020). Randomized placebo-controlled trial showing safety and tolerability data for a novel compound producing regioselective enhancement of cortical noradrenaline, dopamine and acetylcholine.
pubmed: 32198802
pmcid: 32198802
Aarsland, D. et al. ANAVEX®2-73 (blarcamesine) Currently in Phase 2b/3 Early Alzheimer’s Disease (AD): analysis of cognitive outcome measures relevant in AD of double-blind, multicenter, placebo-controlled phase 2 clinical trial in 132 patients with Parkinson’s disease dementia. https://www.anavex.com/wp-content/uploads/2020/11/CTAD-Anavex-PDD-001-Topline-data-Presentation-2020.pdf (2020).
Alam, J. J. et al. The p38α kinase inhibitor neflamapimod significantly improves cognition in patients with mild-to-moderate dementia with Lewy bodies (DLB) [abstract LB22]. J. Prev. Alzheimers Dis. 7, S2–S54, (2020).
Biundo, R. et al. Double-blind randomized trial of tDCS versus sham in Parkinson patients with mild cognitive impairment receiving cognitive training. Brain Stimul. 8, 1223–1225 (2015).
pubmed: 26319357
pmcid: 26319357
Manenti, R. et al. Mild cognitive impairment in Parkinson’s disease is improved by transcranial direct current stimulation combined with physical therapy. Mov. Disord. 31, 715–724 (2016).
pubmed: 26880536
pmcid: 26880536
Willis, A. W. et al. Predictors of survival in patients with Parkinson disease. Arch. Neurol. 69, 601–607 (2012).
pubmed: 22213411
pmcid: 22213411
Backstrom, D. et al. Early predictors of mortality in parkinsonism and Parkinson disease: a population-based study. Neurology 91, e2045–e2056 (2018).
pubmed: 30381367
pmcid: 30381367
Martinez-Martin, P., Rodriguez-Blazquez, C., Kurtis, M. M., Chaudhuri, K. R. & Group, N. V. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov. Disord. 26, 399–406 (2011). Study using the NMSS to assess the impact of non-motor symptoms on the HRQOL of patients with PD.
pubmed: 21264941
pmcid: 21264941
Martinez-Martin, P. An introduction to the concept of “quality of life in Parkinson’s disease”. J. Neurol. 245, S2–S6 (1998).
pubmed: 9617714
pmcid: 9617714
Peto, V., Jenkinson, C., Fitzpatrick, R. & Greenhall, R. The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual. Life Res. 4, 241–248 (1995).
pubmed: 7613534
pmcid: 7613534
Jenkinson, C., Fitzpatrick, R., Peto, V., Greenhall, R. & Hyman, N. The PDQ-8: development and validation of a short-form parkinson’s disease questionnaire. Psychol. Health 12, 805–814 (1997).
EuroQol Group. EuroQol — a new facility for the measurement of health-related quality of life. Health Policy 16, 199–208 (1990).
Zarit, S. H., Reever, K. E. & Bach-Peterson, J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist 20, 649–655 (1980).
pubmed: 7203086
pmcid: 7203086
Yu, J., Yap, P. & Liew, T. M. The optimal short version of the Zarit Burden Interview for dementia caregivers: diagnostic utility and externally validated cutoffs. Aging Ment. Health 23, 706–710 (2019).
pubmed: 29553806
pmcid: 29553806
Hurt, C. S. et al. Identifying barriers to help-seeking for non-motor symptoms in people with Parkinson’s disease. J. Health Psychol. 24, 561–571 (2019).
pubmed: 28810364
pmcid: 28810364
Lawson, R. A. et al. Cognitive decline and quality of life in incident Parkinson’s disease: the role of attention. Parkinsonism Relat. Disord. 27, 47–53 (2016).
pubmed: 27094482
pmcid: 27094482
Morley, D. et al. Factors influencing quality of life in caregivers of people with Parkinson’s disease and implications for clinical guidelines. Parkinsons Dis. 2012, 190901 (2012).
pubmed: 23316414
pmcid: 23316414
Forsaa, E. B. et al. A 12-year population-based study of psychosis in Parkinson disease. Arch. Neurol. 67, 996–1001 (2010).
pubmed: 20697051
pmcid: 20697051
Pedersen, K. F., Larsen, J. P., Alves, G. & Aarsland, D. Prevalence and clinical correlates of apathy in Parkinson’s disease: a community-based study. Parkinsonism Relat. Disord. 15, 295–299 (2009).
pubmed: 18801696
pmcid: 18801696
Riedel, O. et al. Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson’s disease. J. Neurol. 257, 1073–1082 (2010).
pubmed: 20140443
pmcid: 20140443
Martinez-Martin, P., Wan, Y. M., Ray Chaudhuri, K., Schrag, A. E. & Weintraub, D. Impulse control and related behaviors in Parkinson’s disease with dementia. Eur. J. Neurol. 27, 944–950 (2020).
pubmed: 32048392
pmcid: 32048392
Martinez-Martin, P. et al. Neuropsychiatric symptoms and caregiver’s burden in Parkinson’s disease. Parkinsonism Relat. Disord. 21, 629–634 (2015).
pubmed: 25892660
pmcid: 25892660
Karlstedt, M., Fereshtehnejad, S. M., Aarsland, D. & Lökk, J. Mediating effect of mutuality on caregiver burden in Parkinson’s disease partners. Aging Ment. Health 24, 1421–1428 (2020).
pubmed: 31140294
pmcid: 31140294
Vatter, S., McDonald, K. R., Stanmore, E., Clare, L. & Leroi, I. Multidimensional care burden in Parkinson-related dementia. J. Geriatr. Psychiatry Neurol. 31, 319–328 (2018).
pubmed: 30244631
pmcid: 30244631
Vatter, S. et al. Care burden and mental Ill health in spouses of people with Parkinson disease dementia and Lewy body dementia. J. Geriatr. Psychiatry Neurol. 33, 3–14 (2020).
pubmed: 31146617
pmcid: 31146617
Leta, V. et al. Parkinson’s disease and post–COVID-19 syndrome: the Parkinson’s long-COVID spectrum. Mov. Disord. https://doi.org/10.1002/mds.28622 (2021).
doi: 10.1002/mds.28622
pubmed: 33890344
pmcid: 33890344
Feigin, V. L. et al. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 16, 877–897 (2017).
Dorsey, E. R. et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 17, 939–953 (2018).
Dorsey, E. R. & Bloem, B. R. The Parkinson pandemic-a call to action. JAMA Neurol. 75, 9–10 (2018).
pubmed: 29131880
pmcid: 29131880
Williams, U., Bandmann, O. & Walker, R. Parkinson’s disease in sub-Saharan Africa: a review of epidemiology, genetics and access to care. J. Mov. Disord. 11, 53–64 (2018).
pubmed: 29860783
pmcid: 29860783
Khalil, H., Chahine, L., Siddiqui, J., Aldaajani, Z. & Bajwa, J. A. Parkinson’s disease in the MENASA countries. Lancet Neurol. 19, 293–294 (2020).
pubmed: 32169157
pmcid: 32169157
Kaiyrzhanov, R. et al. Parkinson’s disease in central Asian and transcaucasian countries: a review of epidemiology, genetics, clinical characteristics, and access to care. Parkinsons Dis. 2019, 2905739 (2019).
pubmed: 31485304
pmcid: 31485304
Nichols, E. et al. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 88–106 (2019).
Giebel, C. “Current dementia care: what are the difficulties and how can we advance care globally?”. BMC Health Serv. Res. 20, 414 (2020).
pubmed: 32398073
pmcid: 32398073
Ferri, C. P. & Jacob, K. S. Dementia in low-income and middle-income countries: different realities mandate tailored solutions. PLoS Med. 14, e1002271 (2017).
pubmed: 28350797
pmcid: 28350797
Dekker, M. C. J. et al. Parkinson’s disease research on the African continent: obstacles and opportunities. Front. Neurol. 11, 512 (2020).
pubmed: 32636796
pmcid: 32636796
Stephan, B. C. M. et al. Prediction of dementia risk in low-income and middle-income countries (the 10/66 Study): an independent external validation of existing models. Lancet Glob. Health 8, e524–e535 (2020).
pubmed: 32199121
pmcid: 32199121
Berg, D. et al. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson’s disease. Mov. Disord. 29, 454–462 (2014).
pubmed: 24619848
pmcid: 24619848
Boeve, B. F. et al. Arguing against the proposed definition changes of PD. Mov. Disord. 31, 1619–1622 (2016).
pubmed: 27492190
pmcid: 27492190
Postuma, R. B. et al. Abolishing the 1-year rule: how much evidence will be enough? Mov. Disord. 31, 1623–1627 (2016).
pubmed: 27666574
pmcid: 27666574
Friedman, J. H. Dementia with Lewy bodies and Parkinson disease dementia: it is the same disease! Parkinsonism Relat. Disord. 46, S6–S9 (2018).
pubmed: 28756177
pmcid: 28756177
Jellinger, K. A. Dementia with Lewy bodies and Parkinson’s disease-dementia: current concepts and controversies. J. Neural Transm. 125, 615–650 (2018). Critical review on the current concepts and controversies in the pathogenesis of DLB and PDD and their possible nosological interrelations, available biological markers, and present and future treatment strategies.
pubmed: 29222591
pmcid: 29222591
Chahine, L. M. et al. Cognition among individuals along a spectrum of increased risk for Parkinson’s disease. PLoS One 13, e0201964 (2018). Study conducted on patients with de novo PD, with idiopathic RBD, with hyposmia, and non-PD LRRK2 and GBA mutation carriers showing that cognitive function is worse among those with RBD, the characteristic most strongly associated with future risk of PD or dementia with Lewy bodies.
pubmed: 30125297
pmcid: 30125297
Rahayel, S. et al. A prodromal brain-clinical pattern of cognition in synucleinopathies. Ann. Neurol. 89, 341–357 (2021).
pubmed: 33217037
pmcid: 33217037
Chahine, L. M. et al. In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease. Neurology 95, e1267–e1284 (2020).
pubmed: 32747521
pmcid: 32747521
Pilotto, A. et al. Plasma NfL, clinical subtypes and motor progression in Parkinson’s disease. Parkinsonism Relat. Disord. 87, 41–47 (2021).
pubmed: 33964785
pmcid: 33964785
Lin, C. H. et al. Plasma alpha-synuclein predicts cognitive decline in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 88, 818–824 (2017).
pubmed: 28550072
pmcid: 28550072
Schmand, B. Why are neuropsychologists so reluctant to embrace modern assessment techniques? Clin. Neuropsychol. 33, 209–219 (2019).
pubmed: 30882285
pmcid: 30882285
McFarthing, K. et al. Parkinson’s disease drug therapies in the clinical trial pipeline: 2020. J. Parkinsons Dis. 10, 757–774 (2020).
pubmed: 32741777
pmcid: 32741777
Mandler, M. et al. Effects of single and combined immunotherapy approach targeting amyloid beta protein and alpha-synuclein in a dementia with Lewy bodies-like model. Alzheimers Dement. 15, 1133–1148 (2019).
pubmed: 31378574
pmcid: 31378574
Valera, E., Spencer, B. & Masliah, E. Immunotherapeutic approaches targeting amyloid-β, α-synuclein, and Tau for the treatment of neurodegenerative disorders. Neurotherapeutics 13, 179–189 (2016).
pubmed: 26494242
pmcid: 26494242
Takamatsu, Y. et al. Combined immunotherapy with “anti-insulin resistance” therapy as a novel therapeutic strategy against neurodegenerative diseases. NPJ Parkinsons Dis. 3, 4 (2017).
pubmed: 28649604
pmcid: 28649604
Kwon, S., Iba, M., Kim, C. & Masliah, E. Immunotherapies for aging-related neurodegenerative diseases-emerging perspectives and new targets. Neurotherapeutics 17, 935–954 (2020).
pubmed: 32347461
pmcid: 32347461
Green, H., Tsitsi, P., Markaki, I., Aarsland, D. & Svenningsson, P. Novel treatment opportunities against cognitive impairment in Parkinson’s disease with an emphasis on diabetes-related pathways. CNS Drugs 33, 143–160 (2019). Review of ongoing clinical trials in patients with PD and dementia, highlighting the multiple pharmacological mechanisms that are targeted to achieve cognitive enhancement, with a specific focus on diabetes-related pathways.
pubmed: 30687888
pmcid: 30687888
Hung, A. Y. & Schwarzschild, M. A. Approaches to disease modification for Parkinson’s disease: clinical trials and lessons learned. Neurotherapeutics 17, 1393–1405 (2020).
pubmed: 33205384
pmcid: 33205384
Hughes, M. & Duffy, C. Public involvement in health and social sciences research: a concept analysis. Health Expect. 21, 1183–1190 (2018).
pubmed: 30159960
pmcid: 30159960
Qamar, M. A., Rizos, A., Stones, L., Meachin, C. & Chaudhuri, K. R. Public and patient involvement (PPI) at King’s: community for research involvement and support for people with Parkinson’s (CRISP). ACNR 16, 17–20 (2016).
de Roos, P. et al. A consensus set of outcomes for Parkinson’s disease from the international consortium for health outcomes measurement. J. Parkinsons Dis. 7, 533–543 (2017).
pubmed: 28671140
pmcid: 28671140
Aarsland, D. et al. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology 72, 1121–1126 (2009).
pubmed: 19020293
pmcid: 19020293
Broeders, M. et al. Evolution of mild cognitive impairment in Parkinson disease. Neurology 81, 346–352 (2013).
pubmed: 23794682
pmcid: 23794682
Pigott, K. et al. Longitudinal study of normal cognition in Parkinson disease. Neurology 85, 1276–1282 (2015).
pubmed: 26362285
pmcid: 26362285
Weintraub, D. et al. Neuropsychiatric symptoms and cognitive abilities over the initial quinquennium of Parkinson disease. Ann. Clin. Transl. Neurol. 7, 449–461 (2020).
pubmed: 32285645
pmcid: 32285645
Leroi, I. et al. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson’s disease. Int. J. Geriatr. Psychiatry 19, 1–8 (2004).
pubmed: 14716693
pmcid: 14716693
Ravina, B. et al. Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study. J. Neurol. Neurosurg. Psychiatry 76, 934–939 (2005).
pubmed: 15965198
pmcid: 15965198
Litvinenko, I. V., Odinak, M. M., Mogil’naya, V. I. & Emelin, A. Y. Efficacy and safety of galantamine (reminyl) for dementia in patients with Parkinson’s disease (an open controlled trial). Neurosci. Behav. Physiol. 38, 937–945 (2008).
pubmed: 18975103
pmcid: 18975103
Leroi, I., Overshott, R., Byrne, E. J., Daniel, E. & Burns, A. Randomized controlled trial of memantine in dementia associated with Parkinson’s disease. Mov. Disord. 24, 1217–1221 (2009).
pubmed: 19370737
pmcid: 19370737
Cerasa, A. & Quattrone, A. The effectiveness of cognitive treatment in patients with Parkinson’s disease: a new phase for the neuropsychological rehabilitation. Parkinsonism Relat. Disord. 21, 165 (2015).
pubmed: 25443555
pmcid: 25443555
Alloni, A., Quaglini, S., Panzarasa, S., Sinforiani, E. & Bernini, S. Evaluation of an ontology-based system for computerized cognitive rehabilitation. Int. J. Med. Inf. 115, 64–72 (2018).
Paris, A. P. et al. Blind randomized controlled study of the efficacy of cognitive training in Parkinson’s disease. Mov. Disord. 26, 1251–1258 (2011).
pubmed: 21442659
pmcid: 21442659
Lawrence, B. J., Gasson, N., Johnson, A. R., Booth, L. & Loftus, A. M. Cognitive training and transcranial direct current stimulation for mild cognitive impairment in Parkinson’s disease: a randomized controlled trial. Parkinsons Dis. 2018, 4318475 (2018).
pubmed: 29780572
pmcid: 29780572
Hanagasi, H. et al. The effects of rasagiline on cognitive deficits in Parkinson’s disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study. Mov. Disord. 26, 1851–1858 (2011).
pubmed: 21500280
pmcid: 21500280
Jack, C. R. Jr. et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 14, 535–562 (2018).
pubmed: 29653606
pmcid: 29653606
Ma, K.-L. et al. The nuclear accumulation of alpha-synuclein is mediated by importin alpha and promotes neurotoxicity by accelerating the cell cycle. Neuropharmacology 82, 132–142 (2014).
pubmed: 23973294
pmcid: 23973294