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1.
Neurology ; 72(16): 1411-6, 2009 Apr 21.
Article in English | MEDLINE | ID: mdl-19380700

ABSTRACT

OBJECTIVE: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity. BACKGROUND: One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain. METHODS: Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 +/- 9.2 years; 55-84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [11C]methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated. RESULTS: The severity of periventricular (R = -0.52, p = 0.04) but not nonperiventricular (R = -0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe (R = -0.58, p = 0.02). CONCLUSIONS: The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH.


Subject(s)
Aging/pathology , Cerebral Cortex/pathology , Cholinergic Fibers/pathology , Cognition Disorders/pathology , Leukoaraiosis/pathology , Acetylcholine/metabolism , Acetylcholinesterase/analysis , Acetylcholinesterase/metabolism , Aged , Aged, 80 and over , Aging/metabolism , Basal Nucleus of Meynert/metabolism , Basal Nucleus of Meynert/pathology , Basal Nucleus of Meynert/physiopathology , Biomarkers/analysis , Biomarkers/metabolism , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Cholinergic Fibers/diagnostic imaging , Cholinergic Fibers/metabolism , Cognition Disorders/diagnostic imaging , Cognition Disorders/metabolism , Female , Humans , Leukoaraiosis/diagnostic imaging , Leukoaraiosis/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Neural Pathways/pathology , Positron-Emission Tomography , Presynaptic Terminals/metabolism , Presynaptic Terminals/pathology
2.
Eur J Neurol ; 15(7): 685-91, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18435767

ABSTRACT

BACKGROUND AND PURPOSE: The diagnosis of Parkinson disease (PD) is made typically on the basis of motor abnormalities. PD is now recognized to have both motor and non-motor manifestations, indicating a need for the development of reliable non-motor diagnostic tests for PD. The aim of the present study was to compare the accuracy of various clinical motor and non-motor tests for the diagnosis of PD. METHODS: Forty-five PD patients (Hoehn and Yahr stages 1-3; mean age 59.5 +/- 10.0 years) and 45 healthy controls matched for gender and age completed a clinimetric motor test battery to assess limb bradykinesia, tremor and balance. Non-motor tests consisted of depression, anxiety and smell identification ratings. Area under the receiver operator characteristic curve (AUC) analysis was used. RESULTS: We found that smell identification was the most accurate predictor of the presence of PD within the overall group of patients and matched control subjects (AUC = 0.886) and also in the subgroups of mild severity (Hoehn and Yahr stages 1-1.5; AUC = 0.923), young-onset (AUC = 0.888) and female PD patients (AUC = 0.797). The second best diagnostic test was the grooved pegboard test for the clinically most affected body side. CONCLUSIONS: We conclude that olfactory function is the most accurate diagnostic predictor within a heterogeneous sample of patients with PD.


Subject(s)
Olfaction Disorders/etiology , Parkinson Disease/diagnosis , Smell , Adult , Aged , Area Under Curve , Case-Control Studies , Female , Humans , Male , Middle Aged , Mood Disorders/etiology , Parkinson Disease/complications , Parkinson Disease/psychology , Psychomotor Performance/physiology , ROC Curve
3.
J Neurol Neurosurg Psychiatry ; 78(6): 641-3, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17507447

ABSTRACT

AIM: To investigate the relationship between ratings of depressive symptoms and in vivo cortical acetylcholinesterase (AChE) activity in subjects with Parkinson's disease (PD) and parkinsonian dementia (PDem). METHODS: Subjects (with PD, n = 18, including subjects with PDem, n = 6, and normal controls, n = 10) underwent [11C]methyl-4-piperidinyl propionate AChE positron emission tomography imaging and clinical assessment including the Cornell Scale for Depression in Dementia (CSDD). RESULTS: Subjects with PD and PDem had higher scores on the CSDD compared with normal controls: 7.3 (5.4) and 2.8 (2.6), respectively (F = 6.9, p = 0.01). Pooled analysis demonstrated a significant inverse correlation between cortical AChE activity and CSDD scores: R = -0.5, p = 0.007. This correlation remained significant after controlling for Mini-Mental State Examination scores. CONCLUSION: Depressive symptomatology is associated with cortical cholinergic denervation in PD that tends to be more prominent when dementia is present.


Subject(s)
Acetylcholinesterase/metabolism , Cholinergic Agents/metabolism , Dementia/physiopathology , Depressive Disorder/physiopathology , Parkinson Disease/physiopathology , Aged , Aged, 80 and over , Cerebral Cortex/physiopathology , Dementia/diagnostic imaging , Dementia/etiology , Depressive Disorder/diagnostic imaging , Depressive Disorder/etiology , Humans , Magnetic Resonance Imaging , Male , Nerve Degeneration/diagnostic imaging , Nerve Degeneration/physiopathology , Neuropsychological Tests , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography , Receptors, Cholinergic/metabolism
4.
J Neurol ; 253(2): 242-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16133720

ABSTRACT

We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer's disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson's disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (-20.9%) and PD (-12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = -0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning.


Subject(s)
Acetylcholinesterase/metabolism , Cerebral Cortex/enzymology , Cognition/physiology , Dementia , Parkinson Disease , Carbon Radioisotopes/pharmacokinetics , Cerebral Cortex/drug effects , Cerebral Cortex/pathology , Dementia/enzymology , Dementia/pathology , Dementia/physiopathology , Denervation , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Memory, Short-Term/physiology , Neuropsychological Tests/statistics & numerical data , Parkinson Disease/enzymology , Parkinson Disease/pathology , Parkinson Disease/physiopathology , Positron-Emission Tomography/methods , Propionates/pharmacokinetics
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