Studies on the incidence of dementia: the European perspective.

Dementing diseases, the most common of which are Alzheimer's disease and vascular dementia, are highly prevalent in Europe. To progress further in the search for the etiology of these diseases, incidence studies are needed. Comparison of the data of such studies will be important; the question of whether they produce comparable and interpretable data is therefore critical. We discuss the methodologic differences between earlier and more recent studies conducted in Europe that may account for some of the variation in the incidence rates of the dementia they report. Issues to be explored in the current European studies on the incidence of dementing diseases are also described.     

Modern medicine

6.30 am. Woken by the alarm clock before the morning chorus.The roads are pretty clear on my way in, so for a change I manageto find a place in the main hospital car park, opposite theone reserved for the director of finance. 7.45 am. A working breakfast with the chief executive andmedical director. Apparently they want me to re-write the sectionabout my unit in the Trust's annual report. Bob, the CEO, commentsthat it is ‘too factual’. Sarah—once my registrar,now the MD—suggests that we should cut out a lot of thetext and replace it with nice photos: she knows a good agencythat     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.     

Neurological examination findings to predict limitations in mobility and falls in older persons without a history of neurological disease

PURPOSE: To estimate the prevalence of neurological signs and their association with limitations in mobility and falls in a sample of older persons without known neurological disease. METHODS: A neurologist examined 818 participants from the InCHIANTI study who were aged > or =65 years and who did not have cognitive impairment, treatment with neuroleptics, and a history of neurological disease. Mobility was assessed as walking speed and self-reported ability to walk at least 1 km without difficulty. Participants were asked to report falls that had occurred in the previous 12 months. RESULTS: Less than 20% (160/818) of participants had no neurological signs. Neurological signs were more prevalent in older participants and those with impaired mobility. When all neurological signs were included in sex-and age-adjusted multivariate models, 10 were mutually independent correlates of poor mobility. After adjusting for age and sex, the number of neurological signs was associated with progressively slower walking speed (P <0.001), a higher probability of reported inability to walk 1 km (P <0.001), and a history of falls (P <0.05). CONCLUSION: Neurological signs are independent correlates of limitations in mobility and falls in older persons who have no clear history of neurological disease.     

A TGF-beta1 polymorphism association with dementia and neuropathologies: the HAAS

The transforming growth factor-beta1 (TGF-beta1) is involved in post-ischemic neuronal rescue and in beta-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-beta1 functional genetic variants. The association of the TGF-beta1+29T-->C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (OR(TC)=0.28, 95% confidence interval (CI): 0.1-0.9; OR(CC)=0.28, CI: 0.1-0.9), microinfarcts (OR(CC)=0.31, CI: 0.13-0.71) and cerebral amyloid angiopathy (OR(CC)=0.48, CI: 0.2-0.9). The CC genotype was associated with an increase risk of neocortical plaques (OR(CC)=4.34, CI: 1.6-11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia.     

Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study

Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01-2.2]), Alzheimer's disease (AD; 1.8 [1.1-2.9]), and vascular dementia (VsD; 2.3 [1.1-5.0]). Individuals with both type 2 diabetes and the APOE epsilon4 allele had an RR of 5.5 (CI 2.2-13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the epsilon4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2-7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6-7.5]) and hippocampus (IRR 2.5 [1.5-3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5-29.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE epsilon4 allele. The neuropathological data are consistent with the clinical results.     

Hippocampal,amygdalar, and global brain atrophy in different apolipoprotein E genotypes

The epsilon4 allele of the APOE gene increases the risk for AD, whereas the epsilon2 allele may be protective. The authors assessed the impact of APOE genotype on hippocampal, amygdalar, and global brain atrophy as putative markers of preclinical AD in a nondemented population. Carriers of epsilon4 had significantly more hippocampal and amygdalar atrophy than epsilon3epsilon3 subjects, but not more global brain atrophy. Carriers of epsilon2 did not have less brain atrophy than epsilon3epsilon3 subjects.     

The impact of migraine on quality of life in the general population: the GEM study

OBJECTIVE: To assess health-related quality of life (HRQOL) in migraineurs in the general population. DESIGN: Cross-sectional study within the context of a population-based study monitoring health characteristics of the Dutch adult population in two municipalities representative of the general population in the Netherlands. Migraine was assessed in a multistaged procedure that included a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. HRQOL was measured with the self-administered RAND 36-item Health Survey (RAND-36), including physical functioning, social functioning, role limitations, and physical perception. HRQOL of migraineurs was compared with that of nonmigraineurs. To compare and study the effect of comorbidity, the authors also identified subjects with asthma or chronic musculoskeletal pain. There were 5998 people with complete data, 620 of whom had migraine in the last year. RESULTS: Compared with nonmigraineurs, significantly more migraineurs had asthma (OR = 1.6; 95% CI 1.1, 2.4) or chronic musculoskeletal pain (OR = 1.7; 95% CI 1.5, 2.1). Migraineurs reported diminished functioning and well-being on all eight domains as compared with nonmigraineurs. HRQOL was inversely related to attack frequency (p < 0.0002). Migraineurs had a poorer HRQOL than did those reporting asthma, except for dimensions concerning physical functioning and general health perception, but they had a better HRQOL than did subjects with chronic musculoskeletal pain. Comorbidity of asthma or chronic musculoskeletal pain in migraine further reduced HRQOL. CONCLUSIONS: Migraineurs report more asthma and chronic musculoskeletal pain. Compared with nonmigraineurs and to others with chronic conditions, migraineurs report compromised physical, mental, and social functioning, particularly those with a high frequency of attack.     

Rhythms of life

Without a doubt, the school teacher who had the most profoundeffect on me was my sixth form English teacher. He had the abilityto excite enthusiasm for the kind of knowledge that at firstseems innately boring. So I came away from his lessons with,among other things, a lifelong fascination with poetic metreand rhythm. Metre and rhythm, he taught, are not the same. Metre is theimplacable drum beat that underlies any piece of verse (exceptingsome modern