12 research outputs found
Presenting symptoms, biomarkers and underlying brain changes in pre-dementia Lewy body and Alzheimer's disease
White matter integrity and cognition in Parkinson's disease: a cross-sectional study
Objective We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinsonâs disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimerâs disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance.
Methods This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group.
Results Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities.
Conclusions In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD
Correlates of Subjective and Mild Cognitive Impairment: Depressive Symptoms and CSF Biomarkers
Aims: To improve early diagnosis of dementia disease, this study investigates correlates of cognitive complaints and cognitive test performance in patients with subjective (SCI) and mild (MCI) cognitive impairment. Methods: Seventy patients from a memory clinic, aged 45-79, with a score of 2 (n = 23) or 3 (n = 47) on the Global Deterioration Scale, were included. CSF biomarkers [Aβ42, total tau (T-tau) and phosphorylated tau (P-tau)], depressive symptoms, cognitive performance, and complaints were examined. Results: Correlation analysis showed that cognitive complaints increased with decreasing cognitive performance in SCI and decreased with decreasing performance in MCI. Linear regression models revealed that cognitive complaints were associated with depressive symptoms in both groups of patients, while cognitive performance was associated with CSF Aβ42 and P-tau in SCI and with T-tau and P-tau in MCI. Conclusion: These results suggest that depressive symptoms are associated with cognitive complaints, while degenerative changes are associated with objective cognitive decline in high-risk predementia states
Early and presenting symptoms of dementia with lewy bodies
To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer's disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. DLB should be suspected in predementia cases with visual hallucination
Early and Presenting Symptoms of Dementia with Lewy Bodies
Background/Aims: To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). Method: Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimerâs disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. Results: Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. Conclusion: DLB should be suspected in predementia cases with visual hallucinations
Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinsonâs disease: a cross-sectional study
Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression
To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng/BACE1 ratio and Amyloid-β 42/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NCâ=â41; predementia ADâ=â66 and LLDâ=â38). LLD comprised LLD AD (nâ=â16), LLD NoAD (nâ=â19), LLD with non-AD typical changes (nâ=â3, excluded). LLD AD (pADJâ<â0.05) and predementia AD (pADJâ<â0.0001) showed significantly higher Ng than NC. BACE1 and Ng/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (pADJâ<â0.001), BACE1 (pADJâ<â0.05) and Ng/BACE1 ratio (pADJâ<â0.01). All groups had significantly lower Aβ 42/40 ratio than NC (predementia AD and LLD AD, pâ<â0.0001; LLD NoAD, pâ<â0.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as âpredementia AD with depressionâ
Impaired synaptic function is linked to cognition in Parkinson's disease
Objective
Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloidâβ species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloidâβ release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloidâβ, and presynaptic deposits of Îąâsynuclein. We expect a correlation between hypometabolism, CSF amyloidâβ, and the synapse relatedâmarkers CSF neurogranin and Îąâsynuclein.
Methods
Thirty patients with mildâtoâmoderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18FâfludeoxyglucoseâPET, and a neuropsychological test battery (repeated for the patients after 2 years).
Results
All subjects had CSF amyloidâβ 1â42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, Îąâsynuclein, and neurogranin. All PET CSF biomarkerâbased cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mildâtoâmoderate Parkinson's disease compared to controls, correlated with amyloidâβ and Îąâsynuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group.
Interpretation
CSF Aβ, Îąâsynuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and Îąâsynuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease