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1.  Autonomic dysfunction in dementia 
There are no studies of autonomic function comparing Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).
To assess cardiovascular autonomic function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38 elderly controls by Ewing's battery of autonomic function tests and power spectral analysis of heart rate variability. To determine the prevalence of orthostatic hypotension and autonomic neuropathies by Ewing's classification.
There were significant differences in severity of cardiovascular autonomic dysfunction between the four types of dementia. PDD and DLB had considerable dysfunction. VAD showed limited evidence of autonomic dysfunction and in AD, apart from orthostatic hypotension, autonomic functions were relatively unimpaired. PDD showed consistent impairment of both parasympathetic and sympathetic function tests in comparison with controls (all p<0.001) and AD (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02). PDD had significantly more impairment than DLB in some autonomic parameters (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02; Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These results were in contrast with AD patients who only showed impairment in one sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic hypotension and autonomic neuropathies was higher in all dementias than in controls (all p<0.05).
Autonomic dysfunction occurs in all common dementias but is especially prominent in PDD with important treatment implications.
PMCID: PMC2117678  PMID: 17178816
2.  α4β2 nicotinic receptor status in Alzheimer's disease using 123I‐5IA‐85380 single‐photon‐emission computed tomography 
Loss of the α4β2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease.
To investigate in vivo changes in this receptor using single‐photon‐emission CT (SPECT) with 123I‐5‐iodo‐3‐[2(S)‐2‐azetidinylmethoxy] pyridine (5IA‐85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the α4β2 receptor.
32 non‐smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I‐5IA‐85380 and perfusion (99mTc‐hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation.
Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I‐5IA‐85380 and 99mTc‐HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD.
Using 123I‐5IA‐85380 SPECT we found changes consistent with significant reductions in the nicotinic α4β2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.
PMCID: PMC2077777  PMID: 17135460
3.  Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies 
Levodopa (L‐dopa) is the gold standard treatment for Parkinson's disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L‐dopa use in patients with parkinsonism and dementia. Therefore, the effect of L‐dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unclear.
To ascertain the acute and long‐term effects of L‐dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson's disease.
Baseline cognitive and motor function was assessed off L‐dopa in patients with Parkinson's disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L‐dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L‐dopa to assess the prolonged effect.
Acute L‐dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson's disease both with and without dementia on L‐dopa at 3 months. Although patients with Parkinson's disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L‐dopa treatment.
The use of L‐dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.
PMCID: PMC2077405  PMID: 16952917
4.  Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies 
A previous cross sectional study found over‐representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD).
(1) To examine rates of cognitive and motor decline over two years in PD (n = 40), PDD (n = 42) and DLB (n = 41) subjects, compared with age matched controls (n = 41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype.
Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non‐demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE −4.5 and −3.9, respectively), compared with PD (−0.2) and controls (−0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (χ2 = 6.7, Fisher's exact test p<0.05).
A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
PMCID: PMC2117449  PMID: 16614017
Lewy body disease; dementia; parkinsonism; motor subtype; progression
5.  APOE and ACE polymorphisms and dementia risk in the older population over prolonged follow-up: 10 years of incidence in the MRC CFA Study 
Age and Ageing  2009;39(1):104-111.
Background: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years.
Methods: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted.
Results: compared to APOE ε3, ε2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1–0.6) and ε4 risk of OR = 2.9 (95% CI = 1.7–4.9) for incident dementia. Compared to ε3/ε3, the ε3/ε4 and ε4/ε4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8–7.3) and OR = 7.9 (95% CI = 1.6–39.2), respectively. The ε3/ε2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1–0.7), and ε2/ε2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1–1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small.
Conclusions: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk.
PMCID: PMC2794361  PMID: 19939808
apolipoprotein-E; angiotensin-1-converting enzyme; population; dementia; old
8.  Somatostatin content and receptors in the cerebral cortex of depressed and control subjects. 
Somatostatin-like immunoreactivity is reduced in the cerebrospinal fluid in depression and this is presumed to reflect alterations in cerebral somatostatinergic systems. We have examined this hypothesis by measuring this immunoreactivity and somatostatin receptors in post-mortem cortical tissue from depressed patients and control subjects. There was no significant difference in the temporal and occipital cortex in somatostatin-like immunoreactivity or in somatostatin receptor affinity and binding capacity between depressed and control groups. It is concluded that there may not be an alteration of cortical somatostatin function in depression.
PMCID: PMC1033085  PMID: 2900292

Results 1-8 (8)