Exploring the Distinct Effect of Age at Onset and Caudate Denervation on Cognitive Deficits in Early Parkinson's Disease.

Older age at onset and baseline caudate dopaminergic denervation are recognized risk factors for cognitive impairment in Parkinson's disease (PD), posing challenges in identifying their relative contribution to cognitive outcomes. The objective of this study was to assess the distinct contribution of age at onset and baseline caudate dopaminergic binding to the early cognitive deficits in PD patients. We examined the relationship between baseline dopaminergic striatal dysfunction (measured using [123I]-FP-CIT SPECT), age at disease onset and neuropsychological performance in 128 drug-naive PD patients, utilizing putaminal and caudate binding values of 77 healthy controls (HC) for a comparative exploration of age-dependent loss of DAT availability. Additionally, we investigated whether age at onset and DAT binding value of the caudate could independently predict cognitive changes over a median of 7-year follow-up. [123I]-FP-CIT-SPECT binding values had a significant negative correlation with age in both PD and HC, but in PD, aging was linked with a steeper slope for the caudate than the putamen. Older age at onset and lower caudate uptake were associated with worse global cognitive function and performance in specific neuropsychological tests at baseline and demonstrated to be significant independent predictors of cognitive dysfunction at follow-up. Our findings confirm a differential age effect on [123I]-FP-CIT binding in the striatal subregions of de novo PD patients. Notably, we found less age-related attrition of dopaminergic binding in the putamen than in the caudate, reflecting likely the superimposition of putaminal compensatory mechanisms and an increased predisposition of old onset PD patients to develop cognitive disturbances.

Supplementing Best Care with Specialized Rehabilitation Treatment in Parkinson's Disease: A Retrospective Study by Different Expert Centers.

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson's disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson's Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson's Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.

Different Patterns of Locus Coeruleus MRI Alteration in Alzheimer's and Dementia with Lewy Bodies.

BACKGROUND: The integrity of Locus Coeruleus can be evaluated in vivo using specific Magnetic Resonance Imaging sequences. While this nucleus has been shown to be degenerated both in post-mortem and in vivo studies in Alzheimer's Disease, for other neurodegenerative dementias such as Dementia with Lewy Bodies this has only been shown ex-vivo. OBJECTIVE: To evaluate the integrity of the Locus Coeruleus through Magnetic Resonance Imaging in patients suffering from Dementia with Lewy Bodies and explore the possible differences with the Locus Coeruleus alterations occurring in Alzheimer's Dementia. METHODS: Eleven patients with Dementia with Lewy Bodies and 35 with Alzheimer's Dementia were recruited and underwent Locus Coeruleus Magnetic Resonance Imaging, along with 52 cognitively intact, age-matched controls. Images were analyzed applying an already developed template-based approach; Locus Coeruleus signal was expressed through the Locus Coeruleus Contrast Ratio parameter, and a locoregional analysis was performed. RESULTS: Both groups of patients showed significantly lower values of Locus Coeruleus Contrast Ratio when compared to controls. A different pattern of spatial involvement was found; patients affected by Dementia with Lewy bodies showed global and bilateral involvement of the Locus Coeruleus, whereas the alterations in Alzheimer's Dementia patients were more likely to be localized in the rostral part of the left nucleus. CONCLUSIONS: Magnetic Resonance Imaging successfully detects widespread Locus Coeruleus degeneration in patients suffering from Dementia with Lewy Bodies. Further studies, in larger cohorts and in earlier stages of the disease, are needed to better disclose the potential diagnostic and prognostic role of this neuroradiological tool.

Alzheimer's Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers.

BACKGROUND: Neurosyphilis-associated cognitive and behavioral impairment- historically coined as "general paralysis of the insane"- share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer's disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-ß deposition. Consequently, accurate classification and timely differential diagnosis may be challenging. OBJECTIVE: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy. METHODS: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases. RESULTS: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD. CONCLUSION: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.

Dissecting the Interplay Between Time of Dementia and Cognitive Profiles in Lewy Body Dementias.

BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are differentiated by the time of onset of cognitive and motor symptoms ('1-year rule'). We explored the neuropsychological continuum of DLB and PDD subjects with different timing of dementia onset. OBJECTIVE: Our aim was to compare the neuropsychological profile of DLB and PDD patients with different timing of dementia onset. METHODS: Neuropsychological findings at the diagnosis of dementia of 66 PDD and 42 DLB patients were retrospectively compared. Patients with PDD were divided into three tertile subgroups according to the time interval between the onset of parkinsonism and dementia (N = 24, 2-4 years; N = 17, 5-7 years; N = 25 ≥8 years, respectively). RESULTS: DLB patients performed worse on the Stroop and semantic fluency tests than PDD, even in comparison to PD with early dementia onset. No significant differences among PDD subgroups were reported. CONCLUSION: Executive and semantic language tests could differentiate DLB and PD patients with earlier development of dementia relative to parkinsonism.

Mild Cognitive Impairment in de novo Parkinson's Disease: Selective Attention Deficit as Early Sign of Neurocognitive Decay.

Background: In the present study, we aimed to better investigate attention system profile of Parkinson's disease-Mild Cognitive Impairment (PD-MCI) patients and to determine if specific attentional deficits are associated with 123I-FP-CIT SPECT. Methods: A total of 44 de novo drug-naïve PD patients [(27) with normal cognition (PD-NC) and 17 with MCI (PD-MCI)], 23 MCI patients and 23 individuals with subjective cognitive impairment (SCI) were recruited at the Clinical Neurology Unit of Santa Chiara hospital (Pisa University Medical School, Italy). They were assessed by a wide neuropsychological battery, including Visual Search Test (VST) measuring selective attention. Performances among groups were compared by non-parametric tests (i.e., Kruskal-Wallis and Mann-Whitney, Bonferroni corrected). Further, Spearman's rank correlations were performed to explore the association between neuropsychological variables and 123I-FP-CIT SPECT data in PD subgroup. Results: PD-MCI patients performed worse on VST than patients with PD-NC (p = 0.002), patients with MCI and individuals with SCI (p < 0.001). The performance of PD-MCI patients on VST significantly correlated with caudate nucleus 123I-FP-CIT SPECT uptake (rho = 0.582, p < 0.05), whereas a negative correlation between such test and 123I-FP-CIT SPECT uptake in the left putamen (rho = -0.529, p < 0.05) was found in PD-NC patients. Conclusions: We suggest that selective attention deficit might be a trigger of cognitive decay in de novo PD-MCI patients. The VST should be routinely used to detect attentional deficits in hospital clinical practice, in the light of its closely association with dopamine depletion of basal ganglia in mildly impaired PD patients.

Connected speech in progressive supranuclear palsy: a possible role in differential diagnosis.

BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical Parkinsonism characterized by motor and neuropsycological disorders. Language could be impaired in PSP patients, also in Richardson variant (PSP-RS). The analysis of connected speech is used in neurodegenerative disorder to investigate different levels of language organization, including phonetic, phonological, lexico-semantic, morpho-syntactic, and pragmatic processing. OBJECTIVE: In our study, we aimed to investigate the language profile, especially connected speech, in early-stage PSP-RS and Parkinson's disease (PD) patients without predominant speech or language disorders. METHODS: Language was assessed using the Screening for Aphasia in NeuroDegeneration (SAND); connected speech analysis was conducted from the picture description subtest. RESULTS: We enrolled 48 patients, 22 PD and 26 PSP (18 PSP-RS and 8 non-RS). PSP-RS patients presented an impairment in language domain, particularly regarding connected speech. PSP-RS patients presented worse performances than PD in different scores. The output of PSP-RS patients was characterized by a reduction in number of sentences and subordinates with respect to PD; PSP presented also more repaired sequences and phonological and lexico-semantic errors than PD. Number of sentences and number of subordinates of the picture description task were identified as predictors of PSP diagnosis. CONCLUSION: In summary, the SAND scale is able to identify language impairment in PSP patients. The analysis of connected speech could highlight some important aspects of language impairment in PSP-RS patients, and it could be helpful in the differential diagnosis with PD.

Clinical Correlates of Cerebral Amyloid Deposition in Parkinson's Disease Dementia: Evidence from a PET Study.

BACKGROUND: Dementia in Parkinson's disease (PDD) is common presumably due to combined neuropathological substrates. Amyloid-ß (Aß) plaques are well described in PDD but their contribution in synucleinopathies is still controversial. OBJECTIVE: To investigate regional [18F]Florbetapir binding and its relative contribution to cognitive dysfunction in a cohort of PDD patients and to test whether PDD patients with comorbid amyloidopathy have different clinical and neuropsychological characteristics. METHODS: 21 PDD patients, 20 with Alzheimer's disease (AD), and 9 control subjects underwent amyloid positron emission tomography (PET) imaging, neurological, and neuropsychological assessment. Radioligand binding was compared across the groups. PDD scans were interpreted qualitatively and semiquantitatively and categorized as positive or negative. Annual longitudinal Mini-Mental State Examination (MMSE) of PDD subjects was retrospectively collected in order to relate Aß burden to the course of cognitive impairment. RESULTS: [18F]Florbetapir PET imaging was positive in 11 PDD patients (52.38%) using the semi-quantitative method. There were no group differences between PDD subjects with increased cortical [18F]Florbetapir (+) and those without (-), according to demographic and clinical parameters. PDD+ performed worse on Digit Span Foward and on Rey Auditory Verbal Learning Test delayed recall than the PDD- with a significant negative correlation between global cortical retention and specific memory tests. Aß load did not correlate with MMSE ratings although PDD+ demonstrated a faster clinical progression of dementia. CONCLUSIONS: Significant Aß deposition is common in PDD patients contributing to memory impairment and driving a faster rate of cognitive decline.