Alberto Villarejo

Retinal Nerve Fiber Layer Thinning in Dementia Associated with Parkinson's Disease, Dementia with Lewy Bodies, and Alzheimer's Disease

Optical coherence tomography is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL). Previous studies have shown that degenerative changes occur in optic nerve fibers and are manifested as thinning of RNLF in patients with Alzheimers disease (AD). However, there are no studies on the thickness of the RNLF in other types of dementia, such as dementia with Lewy bodies and dementia associated with Parkinsons disease. In this study, patients fulfilling diagnostic for AD (n = 10), dementia with Lewy bodies (n = 10), dementia associated with Parkinsons disease (n = 10), and cognitively normal age-matched controls (n = 10) underwent optical coherence tomography examinations to measure RNLF thickness. There was a significant decrease in RNLF thickness in each type of dementia compared to the control group (Mann-Whitney test, all p < 0.001). Although patients with dementia with Lewy bodies may have a greater thinning than both patients with AD and dementia associated with Parkinsons disease, the differences were statistically nonsignificant (Kruskal-Wallis test, p = 0.525). The thickness of the RNLF correlated significantly (p < 0.001) with both the Mini-Mental State Examination and the Mattis Dementia Rating Scale scores in all types of dementia; that is to say, the greater the cognitive deterioration, the greater the reduction of thickness of the RNLF. The findings from this study show that retinal involvement measured by optical coherence tomography may also be present in non-AD dementias.

Mortality from Parkinson's Disease: A Population-Based Prospective Study (NEDICES)

Most studies of mortality in Parkinsons disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinsons disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population‐based study in which Parkinsons disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinsons disease at baseline (1994–1995). Thirteen‐year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow‐up of 12.0 years (range, 0.04–14.8 years), including 66 of 81 subjects (81.5%) with Parkinsons disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinsons disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinsons disease (hazard ratio, 2.29; 95% confidence interval, 1.80–2.93; P < .001) versus subjects without Parkinsons disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinsons disease (hazard ratio, 1.75; 95% CI, 1.32–2.31, P < .001). In additional Cox models, Parkinsons disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40–4.90; P < .001). In this prospective population‐based study, Parkinsons disease was an independent predictor of mortality in the elderly. Parkinsons disease patients with dementia had particularly high risks of mortality.

Population-based case–control study of cognitive function in early Parkinson's disease (NEDICES)

BACKGROUND Population-based assessments of cognitive function in patients with early Parkinsons disease (PD) are rare. We examined whether patients with early PD have cognitive deficits when compared with matched controls METHODS All participants were age 65 years or older (median=76 years) and were enrolled in the Neurological Disorders in Central Spain (NEDICES) study in central Spain. We identified all participants with early PD (<5 years duration) (N=46). These were matched to 138 controls. Neuropsychological test scores were compared in PD patients vs. controls. In logistic regression models, we adjusted for the effects of confounding variables. In these models, the dependent variable was the neuropsychological test score (lowest quartile vs. all other quartiles) and the independent variable was PD vs. control. RESULTS Sixteen of 46 patients (34.8%) with early PD were previously undiagnosed. Subjective memory complaint was present in 27 (58.7%) PD patients vs. 51 (37.0%) controls (p=0.010). In logistic regression models that adjusted for gender, education, and depressive symptoms or antidepressant use, PD patients performed less well on the 37-item version of the Mini-Mental State Examination (p=0.04), animal (p<0.001) and fruit fluency (p=0.04) as well as in a delayed free recall memory test (p=0.04) than controls. CONCLUSIONS In this population-based sample of older patients with early PD, the rate of subjective and object cognitive impairment was appreciable. Patients with PD of less than five years duration performed relatively poorly on tests of global cognition, verbal fluency and memory. Clinicians should be vigilant to these cognitive difficulties even in the early stages of PD.

Spontaneous carotid and vertebral artery dissection in children

Carotid and vertebral artery dissection is a rarely reported cause of stroke in childhood and adolescence, especially if there is not a direct trauma to the neck. Four patients, under 15 years of age, presented with an internal carotid artery dissection, and one patient presented with a vertebral artery dissection. They were all making a physical effort when the event occurred. The five patients had ischemic symptoms, and in two the events were preceded by transient ischemic attacks. Headache was associated in four patients. The diagnosis was made by magnetic resonance imaging and angiography, which included transfemoral angiography in two patients. All improved before leaving the hospital, and four patients did not suffer recurrent episodes. The diagnostic accuracy of artery dissection has improved because of noninvasive neuroimaging testing, but it should still be suspected in any pediatric ischemic stroke, especially if there is headache or cervical pain associated.

Dementia-Associated Mortality at Thirteen Years in the NEDICES Cohort Study

To evaluate the mortality, thirteen years after the baseline wave (1994), of participants suffering dementia in the Neurological Disorders in Central Spain (NEDICES) Cohort Study, we conducted a population-based cohort study in the elderly (65 years and more) with 5,278 screened participants at baseline. Mortality has been evaluated by means of the National Death Registry of Spain at 1-5-2007, 13 years after enrolment. Coxs proportional hazards regression models were used to evaluate the hazard of death according to dementia severity and type, adjusting for potential covariates (gender, age, level of education, and co-morbidity). Survival was estimated using Kaplan-Meier method. Of the 5,278 participants screened at baseline, 306 had dementia. Mortality at 13 years was: 275 deaths (89.9%) in dementia subjects; and 2,426 (49.0%) in subjects without dementia. Mortality was higher and statistically significant in dementia subjects. The degree of dementia (DSM-III-R) correlated with the risk of mortality, from mild (HR = 2.23; CI: 1.77-2.82) to moderate (HR =3.10; CI: 2.47-3.89) and severe dementia (HR = 4.98; CI: 3.85-6.44). Survival was similar in Alzheimers disease and vascular dementia. Factors associated with higher mortality in Cox proportional hazard models were older age, male gender, and comorbidity. Using Population Attributable risk (PAR%), dementia was related to 11.3% of all deaths. Dementia intensity increases the mortality risk at ten years in the NEDICES Study as in other cohort studies. Age, gender, and co-morbidity are associated with higher mortality in dementia patients. Almost one third of deaths in persons over 85 years-old could be attributable to dementia.

Mirrored-self misidentification in a patient without dementia: evidence for right hemispheric and bifrontal damage

Mirrored-self misidentification, often referred as the ‘mirror sign’, is a delusion characterized by the inability to recognize ones own reflected image, often associated with the intact capacity to recognize others in the mirror. It has been described mainly in moderate or severe dementia, especially Alzheimers disease. In the few reported cases without global cognitive impairment, right hemispheric and frontal dysfunctions have been described. We report a 90-year-old man with abrupt onset of the mirror sign after a minor right hemispheric ischemic stroke. Neuropsychological testing revealed preserved cognitive capacities, except for mild to moderate impairment of visuospatial skills, suggesting right hemisphere dysfunction. Neuroimaging showed a small right dorsolateral frontal infarct, and bifrontal encephalomalacia, consistent with a past history of head trauma. Scattered ischemic white matter lesions in posterior periventricular regions were also seen. It seems that the mirror sign is a multifactorial phenomenon that usually requires right hemispheric dysfunction (perceptual abnormalities, loss of familiarity) and frontal damage (loss of judgement and inability to correct wrong beliefs). The right frontal dorsolateral prefrontal cortex seems to have a crucial role in self-recognition.

Cause of death in mild cognitive impairment: a prospective study (NEDICES).

Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause‐specific mortality need to be explored. To examine short‐term mortality (5 years), long‐term mortality (13 years) and cause‐specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort.

Gabapentin for painful legs and moving toes syndrome.

Short Reports observed in disease processes with neuronal loss or damage, such as stroke, hypoxia, dementia, and multiple sclerosis. An NAA decrease is irreversible if associated with neuronal cell loss, but it may be reversible if associated with nerve fibers. Cho has its resonance peak at 3.2 ppm and is a cell membrane and myelin marker. An increase in Cho is associated with a release of Cho from its pool, such as cell membrane and myelin, which occurs in various pathologic processes, such as acute myelin breakdown and brain edema [5, 6] in an acute condition and increased cellular density in a chronic condition. The present case showed an increase in Cho. As mentioned above, this pattern of acute proton MRS abnormality suggests either demyelination or brain edema. The typical example of acute demyelination is acute multiple sclerosis, in which both increased Cho and decreased NAA are observed. As the MRS in our present case lacks the latter finding, its MRI abnormality may be that of brain edema, which is also consistent with its asymptomatic presentation. Further studies are needed, however, to delineate which type of edema is associated with the MRS abnormality seen in our case.

Risk of Incident Dementia in Drug-Untreated Arterial Hypertension: A Population-Based Study

Arterial hypertension in midlife may increase the risk of late-life dementia. Notably, there is conflicting data as to whether hypertension in the elderly (age 65 years and older) is a risk factor for dementia and Alzheimers disease (AD). We determined whether drug-untreated hypertension was associated with a higher risk of incident dementia and AD. In a population-based study of older people in central Spain (NEDICES), non-demented participants were followed prospectively. Dementia at follow-up was diagnosed using DSM-IV criteria. Using Cox proportional hazards models, the risk of dementia was estimated in participants with drug-untreated hypertension and in participants with drug-treated hypertension versus controls. The 3,824 participants had a mean duration of follow-up of 3.2 years. Sixty-two (3.3%) of 1,870 participants without baseline hypertension developed incident dementia versus 78 (4.7%) of 1,657 with drug-treated, baseline hypertension and 19 (12.0%) with drug-untreated, baseline hypertension. In an unadjusted Cox model, risk of dementia was increased in participants with drug-untreated hypertension (relative risk [RR] =1.93, 95% confidence interval [CI]=1.15–3.23, p = 0.01) and in participants with drug-treated hypertension (RR =1.43, 95% CI= 1.02–2.0, p =0.035) versus participants without hypertension (reference group). In a fully adjusted Cox model, the risk of dementia remained increased in participants with drug-untreated hypertension (RR =2.38, 95% CI =1.32–4.29, p=0.004). Results were similar for risk of AD. Our results suggest that drug-untreated hypertension may be an independent risk factor for dementia and AD in the elderly.

Memory impairment in a simple recall task increases mortality at 10 years in non‐demented elderly

To evaluate whether memory impairment detected in the three‐word delayed recall task of the Mini‐Mental State Examination (MMSE) increases the risk of mortality.