Premotor cognitive status in a cohort of incident Parkinson disease patients (NEDICES)

Sánchez‐Ferro, Álvaro; Benito‐León, Julián; Mitchell, Alex J.; Louis, Elan D.; Posada, Ignacio J.; Trincado, Rocío; Villarejo, Alberto; Bermejo‐Pareja, Félix

doi:10.1016/j.jns.2011.05.007

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…In the current research, we have demonstrated that cognitive test scores in prevalent PD declined at a rate above and beyond the rate observed in both premotor PD and control groups (among whom the rates of progression were similar). This observation is in agreement with some of our prior results, 13 suggesting that overt, clinically significant cognitive dysfunction rarely occurs in the very early premotor phase of PD. This is not necessarily inconsistent with the observation that some impairment may appear a few years after the motor manifestations of PD are evident, as we also previously found.…”

Section: Discussionsupporting

confidence: 94%

“…Of the patients with PD, 28.4% had not been diagnosed prior to the start of the study and would not have been recruited if we had relied exclusively on practitioner referrals . We recently reported that cognitive dysfunction is not typically a premotor feature of subjects who subsequently develop PD in NEDICES . However, it is not known whether cognitive decline progresses in premotor PD cases at a faster rate than in elders without this disease.…”

mentioning

confidence: 99%

“…11 We recently reported that cognitive dysfunction is not typically a premotor feature of subjects who subsequently develop PD in NEDICES. 13 However, it is not known whether cognitive decline progresses in premotor PD cases at a faster rate than in elders without this disease.…”

mentioning

confidence: 99%

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Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

et al. 2012

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Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population-based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non-PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994-95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997-98, but not at baseline). A 37-item version of the Mini-Mental State Examination (37-MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37-MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3-year follow-up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal-Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD.

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Section: Discussionsupporting

confidence: 94%

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confidence: 99%

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Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

et al. 2012

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“…Furthermore, it is notable that these mice exhibit profound fine/sensorimotor deficits and synaptic dysfunction long before α-syn accumulation/aggregation or obvious motor symptoms are evident. This finding is especially important because PD patients often present with sensorimotor and non-motor symptoms long before the onset of motor dysfunction [39], [40], [41], [42]. Although the exact mechanisms responsible for eliciting these impairments are unknown, our findings suggest this model may be useful for examining the underlying cause of pre-motor symptoms in PD patients.…”

Section: Discussionmentioning

confidence: 84%

Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

et al. 2013

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Parkinson's disease (PD) pathology is characterized by the formation of intra-neuronal inclusions called Lewy bodies, which are comprised of alpha-synuclein (α-syn). Duplication, triplication or genetic mutations in α-syn (A53T, A30P and E46K) are linked to autosomal dominant PD; thus implicating its role in the pathogenesis of PD. In both PD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of protein aggregates (i.e., α-syn) and neurodegeneration. Characterization of the timing and nature of symptomatic dysfunction is important for understanding the impact of α-syn on disease progression. Furthermore, this knowledge is essential for identifying pathways and molecular targets for therapeutic intervention. To this end, we examined various functional and morphological endpoints in the transgenic mouse model expressing the human A53T α-syn variant directed by the mouse prion promoter at specific ages relating to disease progression (2, 6 and 12 months of age). Our findings indicate A53T mice develop fine, sensorimotor, and synaptic deficits before the onset of age-related gross motor and cognitive dysfunction. Results from open field and rotarod tests show A53T mice develop age-dependent changes in locomotor activity and reduced anxiety-like behavior. Additionally, digigait analysis shows these mice develop an abnormal gait by 12 months of age. A53T mice also exhibit spatial memory deficits at 6 and 12 months, as demonstrated by Y-maze performance. In contrast to gross motor and cognitive changes, A53T mice display significant impairments in fine- and sensorimotor tasks such as grooming, nest building and acoustic startle as early as 1–2 months of age. These mice also show significant abnormalities in basal synaptic transmission, paired-pulse facilitation and long-term depression (LTD). Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments similar to PD patients and may provide useful endpoints for assessing novel therapeutic interventions for PD.

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“…The rate of cognitive decline in the premotor phase of PD compared to controls is similar based on two population-based studies,173,174 suggesting that global cognitive dysfunction may not occur in premotor PD. Generally, in PD, ~25% of nondemented patients have mild cognitive impairment (MCI)175 and up to 80% of all PD patients will eventually develop dementia 176.…”

Section: Cognitive Impairment In Untreated Pdmentioning

confidence: 90%

Neuropsychiatric symptoms in untreated Parkinson’s disease

Szatmári

Illigens

Siepmann

et al. 2017

NDT

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Neuropsychiatric and cognitive symptoms are common in Parkinson’s disease (PD) and may precede and exceed motor symptoms as major factors impacting disease course and quality of life. Neuropsychiatric symptoms (NPS) in PD are various and are attributed to pathologic changes within multiple brain regions, to psychological stress, and to adverse effects of dopamine replacement therapy. Sleep disorders and mood symptoms such as apathy, depression, and anxiety may antedate the development of motor symptoms by years, while other NPS such as impulse control disorders, psychosis, and cognitive impairment are more common in later stages of the disease. Few studies report on NPS in the early, untreated phase of PD. We reviewed the current literature on NPS in PD with a focus on the early, drug-naive stages of PD. Among these early disease stages, premotor and early motor phases were separately addressed in our review, highlighting the underlying pathophysiological mechanisms as well as epidemiological characteristics, clinical features, risk factors, and available techniques of clinical assessment.

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Premotor cognitive status in a cohort of incident Parkinson disease patients (NEDICES)

Cited by 6 publications

References 42 publications

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

Neuropsychiatric symptoms in untreated Parkinson’s disease

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Premotor cognitive status in a cohort of incident Parkinson disease patients (NEDICES)

Cited by 6 publications

References 42 publications

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Behavioral Characterization of A53T Mice Reveals Early and Late Stage Deficits Related to Parkinson’s Disease

Neuropsychiatric symptoms in untreated Parkinson&rsquo;s disease

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Product

Resources

About

Neuropsychiatric symptoms in untreated Parkinson’s disease