ABSTRACT
BACKGROUND: Cerebral white matter changes (WMC) represent cerebrovascular disease (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies (DLB). Predictors of treatment response are controversial. OBJECTIVE: To investigate the effect of WMC severity on rate of progression of dementia during treatment with ChEIs. METHODS: CT or MRI brain scans were rated for WMC severity in 243 patients taking ChEIs for dementia. Raters were blind to patients' clinical risk factors, dementia subtype and course of illness. Effects of WMC severity on rates of decline in cognition, function and behaviour were analysed for 140 patients treated for 9 months or longer. Analysis was performed for this group as a whole and within diagnostic subgroups AD and DLB. The main outcome measure was rate of change in Mini Mental State Examination (MMSE) score. Secondary measures were rates of change in scores on the Cambridge Cognitive Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton Assessment Procedures for the Elderly - Behaviour Rating Scale (CAPE-BRS). RESULTS: There was no significant association between severity of WMC and any specified outcome variable for the cohort as a whole or for patients with AD. In patients with DLB, higher WMC scores were associated with more rapid cognitive decline. CONCLUSIONS: Increased WMC severity does not influence clinical response to ChEI treatment in AD, but may hasten deterioration in ChEI-treated patients with DLB.
Subject(s)
Brain/pathology , Cholinesterase Inhibitors/therapeutic use , Dementia/drug therapy , Dementia/pathology , Aged , Aged, 80 and over , Cognition Disorders/etiology , Cognition Disorders/pathology , Cognition Disorders/prevention & control , Dementia/psychology , Disease Progression , Female , Follow-Up Studies , Geriatric Assessment/methods , Humans , Magnetic Resonance Imaging , Male , Psychiatric Status Rating Scales , Retrospective Studies , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.
Subject(s)
Corpus Striatum/metabolism , Lewy Body Disease/metabolism , Membrane Glycoproteins/metabolism , Membrane Transport Proteins/metabolism , Nerve Tissue Proteins/metabolism , Parkinson Disease/metabolism , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Corpus Striatum/diagnostic imaging , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins , Functional Laterality , Humans , Lewy Body Disease/diagnosis , Lewy Body Disease/diagnostic imaging , Neurologic Examination , Occipital Lobe/diagnostic imaging , Occipital Lobe/metabolism , Parkinson Disease/diagnosis , Parkinson Disease/diagnostic imaging , Psychiatric Status Rating Scales , Putamen/diagnostic imaging , Putamen/metabolism , Severity of Illness Index , Striatonigral Degeneration/diagnostic imaging , Striatonigral Degeneration/metabolism , Tomography, Emission-Computed, Single-Photon , TropanesABSTRACT
BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.
