Alzheimer's pathology targets distinct memory networks in the ageing brain

Alzheimer’s disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer’s disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer’s disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20–93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer’s disease dementia (65–95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer’s disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = −3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = −0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer’s disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer’s disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function

Insomnia and its correlates in a representative sample of the Greek population

<p>Abstract</p> <p>Background</p> <p>Insomnia is a major public health concern affecting about 10% of the general population in its chronic form. Furthermore, epidemiological surveys demonstrate that poor sleep and sleep dissatisfaction are even more frequent problems (10-48%) in the community. This is the first report on the prevalence of insomnia in Greece, a southeastern European country which differs in several socio-cultural and climatic aspects from the rest of European Community members. Data obtained from a national household survey (n = 1005) were used to assess the relationship between insomnia symptoms and a variety of sociodemographic variables, life habits, and health-related factors.</p> <p>Methods</p> <p>A self-administered questionnaire with questions pertaining to general health and related issues was given to the participants. The Short Form-36 (Mental Health subscale), the Athens Insomnia Scale (AIS) as a measure of insomnia-related symptoms, and the International Physical Activity Questionnaire (IPAQ) were also used for the assessment.</p> <p>Results</p> <p>The prevalence of insomnia in the total sample was 25.3% (n = 254); insomnia was more frequent in women than men (30.7% vs. 19.5%) and increased with age. Multiple regression analysis revealed a significant association of insomnia with low socio-economical status and educational level, physical inactivity, existence of a chronic physical or mental disease and increased number of hospitalizations in the previous year.</p> <p>Conclusions</p> <p>The present study confirms most findings reported from other developed countries around the world regarding the high prevalence of insomnia problems in the general population and their association with several sociodemographic and health-related predisposing factors. These results further indicate the need for more active interventions on the part of physicians who should suspect and specifically ask about such symptoms.</p

Benzodiazepine use among adults residing in the urban settlements of Karachi, Pakistan: A cross sectional study

<p>Abstract</p> <p>Background</p> <p>There are hardly any studies carried out in Pakistan on the usage of benzodiazepines at the level of community. This research was aimed to determine the frequency of benzodiazepine use, along with its associations with socio-demographic and clinical characteristics among community dwelling adults, residing in two urban settlements of Karachi, Pakistan.</p> <p>Methods</p> <p>We performed a cross sectional study from August 2008 to December 2009, in 2 areas of Karachi, namely Garden and Sultanabad. We followed the systematic sampling strategy to randomly select the households, with an adult of either sex and of age 18 years or more. Data collection was carried out through interview, using a pre-tested questionnaire, with items on socio-demographic position, medical history and benzodiazepine use. Student's t-test and χ²test was employed to determine the associations between socio-demographic and clinical characteristics, and their relationship with benzodiazepine use was determined using applied logistic regression.</p> <p>Results</p> <p>The overall percentage of benzodiazepine consumption was estimated to be 14%. There were significantly more benzodiazepine users in the peri-urban Sultanabad community to the urban community of Garden (p-value = 0.001). The mean age (± SD) for users was 51.3 (± 15.6) years compared to 37.1 (± 14.4) years among non-users. Bromazepam was the most widely used benzodiazepine (29%); followed by diazepam, with a median duration on primary use being 144 weeks (IQR = 48-240). The adjusted logistic regression model revealed that increasing age, location, female sex, unemployment and psychiatric consultation were associated with increased likelihood of benzodiazepine use.</p> <p>Conclusion</p> <p>We believe the unregulated over-the-counter sales of benzodiazepines and social conditions might be playing a role in this high consumption of benzodiazepines in the community.</p

Current benzodiazepine issues

This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronicaly, and although this does not appear to result in dose escalation or other evidence of “psychological dependence,” physiological dependence can result in patient discomfort if drug use is abruptly discontiniued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46347/1/213_2005_Article_BF02245824.pd

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p &lt; 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival