In The New York Times: Obituary
In The Economist: Obituary
Her 1986 Nobel Lecture: Nobel Lecture
There are many reasons to develop telemedicine clinics for assessment and management of dementia. Time constraints, location, and poor weather conditions can all impact on the ability of patients and providers to attend rural clinics. The utility of telemedicine in the diagnosis of dementia and subsequent follow-up appears promising in the literature, as it provides a viable means of assessing cognition in patients in remote areas with limited access to medical specialists.
This study explored the feasibility of introducing a telemedicine memory disorder follow-up clinic in a rural community. The evaluation of 32 clinic sessions found high levels of satisfaction, with over 90% of physicians and patients indicating that they'd be willing to use video conferencing again. Physicians overwhelmingly felt the sessions provided enough information to assist in clinical decision-making (96%), and patients and CCAC Case Managers/Geriatric Assessors felt able to present the same information by video conferencing as in person (92% for both groups). The telemedicine clinic provided a number of favourable results such as: timely access to specialist care in the patient's own community; fewer cancelled clinics; enhanced care transitions between the follow-up clinic and primary care with the support of a case manager/geriatric assessor; and enhanced follow-up for a complex patient population. In addition, the telemedicine initiative freed up spaces for "in-person" clinics. This allowed them to focus on new patient assessments.
The high satisfaction rates amongst all key stakeholders affirm that telemedicine is a viable option and worth continued efforts at shaping and developing, particularly in regions where local physician specialists are a scare resource.
PMID: 23259023 [PubMed - in process]
We investigated the earliest neuropsychological changes in Alzheimer's disease (AD) by comparing the baseline performance of 29 individuals who subsequently developed AD within an average of 7.91 ± 2.70 years with 29 pairwise-matched individuals who remained cognitively healthy (NC). We hypothesized that subtle, qualitative changes in cognition precede clinical AD by several years, and therefore examined subjective as well as standard quantitative measures of cognition, in addition to subjective estimates of mood and medical status. Participants were selected from the 825 members of the longitudinal BASEL study (BAsel Study on the ELderly), all of whom had been ApoE-genotyped and received comprehensive bi-annual neuropsychological assessments. Within 13 years, 29 were diagnosed with probable AD. Each individual who progressed to AD (AD-P) was pairwise matched to a NC participant based on age, education, demographic status, observation period, and, importantly, ApoE genotype. A regression analysis using the lasso technique identified which of 115 neuropsychological variables best discriminated baseline NC from baseline AD-P performance. This analysis yielded eleven neuropsychological variables that optimally discriminated the two groups (correct classification rate: 60.4%): 1) Intrusions and 2) response bias in verbal learning and memory tasks; 3) delayed figure recall; 4-6) three Wechsler Adult Intelligence Scale (WAIS) Block Design subtest variables; 7-8) number of errors and repetitions on letter fluency; and 9-11) self-report of memory problems, a feeling of sadness, and cardiac problems. These results suggest that the preclinical neuropsychological cascade to AD includes subtle but identifiable qualitative impairments in verbal and visual memory, visuospatial processing, error control, and subjective neuropsychological complaints.
PMID: 23254631 [PubMed - as supplied by publisher]
"Useful Neuropsychology Texts"
Read the blog entry
Your brain on pseudoscience: the rise of popular neurobollocks
By Steven Poole
06 September 2012
"The “neuroscience” shelves in bookshops are groaning. But are the works of authors such as Malcolm Gladwell and Jonah Lehrer just self-help books dressed up in a lab coat?"
The objective of this study is to examine whether neuron loss occurs in SAMP8 and whether neuron loss is correlated with cognitive deficits of these mice. Neuronal loss is considered as one of the most important pathological hallmarks of Alzheimer disease (AD). In addition to the early-onset, irreversible, severe deficits of learning and memory, SAMP8 mice show spontaneous age-related neurodegenerative changes and other characteristics seen in AD patients, such as amyloid plaques and neurofibrillary tangles. However, it is still unknown whether neuron loss occurs in SAMP8 and whether neuron loss is correlated with cognitive deficits of these mice. We employed 8-month-old SAMP8 and SAMR1 mice to investigate the cognitive function and neuron numbers. The behaviors were examined by the grading score of senescence and Morris water maze (MWM) test, the neuron number in hippocampus was estimated by the optical fractionator technique. The grading score of senescence and MWM test demonstrated that SAMP8 exhibited notable age-related changes in appearance and cognitive function. Moreover, severe hippocampal neuron loss was found in SAMP8 as determined by the optical fractionator stereological method. Compared to SAMR1, the neuron number of CA1, CA3 and DG in SAMP8 was reduced by 15.6, 19.8 and 20.2 %, respectively, and the neuron loss in hippocampus was associated with cognitive deficits. Collectively, these results suggest that hippocampal neuronal loss is well correlated with learning and memory deficits in SAMP8 and SAMP8 represents an important mouse model for AD.
PMID: 22872064 [PubMed - as supplied by publisher]
Corporate Press Release: Read the release
Commentary from the In The Pipeline blog: In The Pipeline
Commentary from Pharmalot: Pharmalot
UPDATED: Pfizer, J&J Alzheimer's drug bapineuzumab flunks out in big PhIII
July 23, 2012
By John Carroll
Examine media reports this week for these results and accompanying analysis and commentary. Those who have been following this clinical-trial program should examine the corporate press release for additional details about the other three Phase III trials in this program (which were not part of today's results).
Caregiving for patients with Alzheimer's disease (AD) is associated with negative outcomes for the caregiver such as depression, anxiety, medical illness, poorer general health and mortality, which further translate into adverse outcomes for the patient. The burden experienced by caregivers of AD patients, both professional and informal, has been found to be positively related to the presence and severity of the patients' neuropsychiatric symptoms, also referred to as the behavioural and psychological symptoms of dementia (BPSD). As such, management of BPSD may help in alleviating caregiver burden. The purpose of this review is to summarize the current literature on the effects of pharmacological interventions for BPSD on the burden of AD patient caregivers. A literature review was conducted, using keywords related to dementia, drug treatment, caregiving and BPSD. Studies were included if they were a randomized controlled trial of a currently marketed drug in AD patients, and included a measure of caregiver burden and BPSD. Twenty-four articles met the eligibility criteria for this review. Cognitive enhancers (cholinesterase inhibitors, memantine) were associated with decreased caregiver burden in some studies, though it is unclear whether the improvements were related to changes in BPSD or cognition and function. Antipsychotics have been associated with decreased caregiver burden in some studies, though variability may be related to disease severity. Other drug treatments, including antidepressants, have also been shown to have inconsistent effects on caregiver burden. Besides the small number of clinical trials that included a measure of caregiver burden, there is large variability in the literature due to differing conceptualizations of caregiver burden and the lack of a recognized gold standard for caregiving burden assessment. It is therefore difficult to draw strong conclusions about whether the pharmacological management of BPSD relieves caregiver burden. Given the importance of caregiver burden and its negative consequences for the caregiver and the patient, future clinical trials should pay more attention to this crucial outcome.
PMID: 22350526 [PubMed - indexed for MEDLINE]
Alzheimer's drug IVIg could halt sufferers' decline
Trial involving 16 patients excites scientists by suggesting treatment prevented deterioration of memory and cognitive skills
Alexandra Topping and agencies
Wednesday 18 July 2012 10.21 BST
"A new treatment for Alzheimer's could halt deterioration in people with early symptoms of the disease, a limited human trial has shown. The treatment, called the "most exciting drug in development" by scientists, is currently prescribed to people with immune system problems but could have a significant impact on the quality of life of Alzheimer's sufferers, the trial suggests.
"The drug, intravenous immunoglobulin (IVIg), prevented the decline in cognitive skills, memory and the ability to live independently, among patients with mild to moderate symptoms of Alzheimer's. Those who took a placebo continued to decline. The small number of patients who took the highest dose of the drug for three years showed no decline in memory."
Here is the AAIC press release: Read the AAIC press release
"Professor Alan Baddeley FRS CBE from the University of York has received this year’s Lifetime Achievement Award from the [British Psychoogical] Society’s Research Board."
Here is the current schedule of press briefings (Pacific Time) for the conference, as cited on the conference website:
Sunday, July 15
7:30 a.m. Gait disturbances and Alzheimer's disease risk/early detection
Monday, July 16
7:30 a.m. Irregular sleep patterns affect cognitive function and dementia risk
Tuesday, July 17
7:30 a.m. Alzheimer's therapies update
Wednesday, July 18
7:30 a.m. AAIC 2012 Developing Topics - including several clinical trials
If you are not attending the conference, you might anticipate being able to access media reports on these topics along this schedule, in addition to overall media coverage of the event.
All eyes and ears will be on clinical trials findings!
However, even if you are a student, this is an excellent annual conference to attend and you will find great interactions with others. Enjoy!
Two decades ago, researchers began discovering rare gene mutations that cause Alzheimer’s disease in all who inherit them. Now, they have found the opposite: a mutation that prevents the devastating brain disorder. The protective mutation also is very rare — it is not the reason most people do not develop Alzheimer’s disease. But what intrigues researchers is how it protects the brain. It does the reverse of what the mutations that cause Alzheimer’s do. Those mutations lead to excessive amounts of a normal substance, beta amyloid, in the brain. The protective mutation slows beta amyloid production, so people make much less.
We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that the BAD-responders had larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.
PMID: 22530263 [PubMed - indexed for MEDLINE]
Objective: The current study examined whether year-to-year variability in cognitive performance differ between individuals cognitively unimpaired and individuals who subsequently develop dementia. Method: Analyses included a case-control sample of Baltimore Longitudinal Study of Aging (BLSA; mean [M] age = 69.90, standard deviation [SD] = 8.92) participants. One hundred and 35 clinically diagnosed demented participants were matched with 135 nondemented participants based on age at initial testing and sex. Cognitive performance was examined using measures of memory, executive function, attention, language, and global mental status performance. Cognitive performance was examined from baseline to 5 years before cognitive impairment (M, assessments = 3.03, SD = 2.80). Results: As compared with unimpaired individuals, individuals diagnosed with dementia had greater variability on measures of attention, executive function, language, and semantic memory at least 5 years before the estimated onset of cognitive impairment, which may be indicative of maladaptive cognitive functioning. The dementia cases, however, had less variability on visual memory than the unimpaired group, which may suggest that these cases had more difficulty learning. Conclusions: These results demonstrate that performance variability indexed over annual or biennial visits may be useful in identifying early signs of subsequent cognitive impairment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).
PMID: 22746310 [PubMed - in process]
"Results from the survey of 146 investors were released late on Tuesday by Mark Schoenebaum, a pharmaceutical analyst for the investment research services group. Wall Street is eagerly awaiting results of the trials and expects huge potential sales if either of the medicines proves able to arrest the progression of the memory-robbing disease.
"Pfizer and Lilly are expected in the third quarter to disclose the main findings from large studies of their respective medicines, bapineuzumab and solanezumab. Complete data are expected to be presented at medical meetings in the fourth quarter.
"The survey responders, on average, gave solanezumab only a 14 percent chance of meeting all the primary goals of its two Phase III studies, compared with an average 21 percent probability for the two big trials of bapineuzumab, Schoenebaum said."
Read the full article
Comments by the Pharmalot blog on this report, from the 20th of June:
Read the blog entry from Pharmalot.
Lenehan ME, Klekociuk SZ, Summers MJ. Absence of a relationship between subjective memory complaint and objective memory impairment in mild cognitive impairment (MCI): is it time to abandon subjective memory complaint as an MCI diagnostic criterion? Int Psychogeriatr. 2012 May 1: 1-10. [Epub ahead of print]
Background: Subjective memory complaints are a requirement in the diagnosis of mild cognitive impairment (MCI) as they are thought to indicate a decline in objective memory performance. However, recent research suggests that the relationship between subjective memory complaint and objective memory impairment is less clear. Thus, it is possible that many people without subjective memory complaints who develop Alzheimer's disease are precluded from a diagnosis of MCI.Methods: The present study examined the relationship between subjective memory complaint assessed using the Multifactorial Memory Questionnaire (MMQ) and objective memory impairment assessed using standard neuropsychological measures in cases of amnestic MCI (n = 48), non-amnestic MCI (n = 27), and unimpaired healthy participants (n = 64).Results: Correlational and regression analyses indicated that subjective memory complaints displayed a poor relationship with objective memory performance. A subsequent discriminant function analysis indicated that subjective memory complaints failed to improve the diagnostic accuracy of MCI and resulted in increased rates of false negative and false positive diagnoses.Conclusion: The results of the present study suggest that a diagnostic criterion of subjective memory complaint reduces the accuracy of MCI diagnosis, resulting in an elevated rate of false positive and false negative diagnoses. The results of this study in conjunction with recent research indicate that a criterion of subjective memory complaint should be discarded from emerging diagnostic criteria for MCI.
PMID: 22717042 [PubMed - as supplied by publisher]
The interaction of brain-derived neurotrophic factor (BDNF) with its tropomyosin-related kinase receptor B (TrkB) is involved in fundamental cellular processes including neuronal proliferation, differentiation and survival as well as neurotransmitter release and synaptic plasticity. TrkB signaling has been widely associated with beneficial, trophic effects and many commonly used psychotropic drugs aim to increase BDNF levels in the brain. However, it is likely that a prolonged increased TrkB activation is observed in many pathological conditions, which may underlie the development and course of clinical symptoms. Interestingly, genetic and pharmacological studies aiming at decreasing TrkB activation in rodent models mimicking human pathology have demonstrated a promising therapeutic landscape for TrkB inhibitors in the treatment of various diseases, e.g. central nervous system (CNS) disorders and several types of cancer. Up to date, only a few selective and potent TrkB inhibitors have been developed. As such, the use of crystallography and in silico approaches to model BDNF-TrkB interaction and to generate relevant pharmacophores represents powerful tools to develop novel compounds targeting the TrkB receptor.
Copyright © 2012. Published by Elsevier Ltd.
PMID: 22705453 [PubMed - as supplied by publisher]
Prospective memory (PM) is the ability to remember to execute delayed intentions. Previous studies indicate that PM is impaired in persons with mild cognitive impairment (MCI) and dementia, but the extent, nature, and cognitive correlates are unclear. A meta-analytic review was, therefore, performed (literature search 1990 to July 2011) on case-control studies on PM in dementia (10 studies, 336 patients, 505 controls) and MCI (7 studies, 225 patients, 253 controls). Differences between event-based and time-based PM and between measures of prospective and retrospective memory were examined, as well as correlations with other cognitive functions. Results showed that patients with dementia or MCI exhibit large deficits in PM (Hedges' d -1.62 [95% confidence interval -1.98 to -1.27; p < .0001] for dementia; -1.24 [-1.51 to -0.995; p < .0001] for MCI; difference dementia vs. MCI: QM = 1.94, p = .16). Impairments were comparable in size for event-based and time-based PM (p > .05), as well as for prospective and retrospective memory (p > .05). PM showed modest correlations with measures of retrospective memory (median r = 0.27) and executive functioning (median r = 0.30). PM appears a valid construct in neuropsychological assessment in patients with dementia or MCI, but more insight is needed in the optimal characteristics of PM tasks to be used in clinical practice. (JINS, 2012, 18, 1-11).
PMID: 22595831 [PubMed - as supplied by publisher]
"Sluggish cognitive tempo" (SCT) is a construct hypothesized to describe a constellation of behaviors that includes daydreaming, lethargy, drowsiness, difficulty sustaining attention, and underactivity. Although the construct has been inconsistently defined, measures of SCT have shown associations with symptoms of attention-deficit/hyperactivity disorder (ADHD), particularly inattention. Thus, better characterization of SCT symptoms may help to better predict specific areas of functional difficulty in children with ADHD. The present study examined psychometric characteristics of a recently developed 14-item scale of SCT (Penny et al., Psychological Assessment 21:380-389, 2009), completed by teachers on children referred for outpatient neuropsychological assessment. Exploratory factor analysis identified three factors in the clinical sample: Sleepy/Sluggish, Slow/Daydreamy, and Low Initiation/Persistence. Additionally, SCT symptoms, especially those loading on the Sleepy/Sluggish and Slow/Daydreamy factors, correlated more strongly with inattentive than with hyperactive/impulsive symptoms, while Low Initiation/Persistence symptoms added significant unique variance (over and above symptoms of inattention) to the predictions of impairment in academic progress.
PMID: 22566025 [PubMed - as supplied by publisher]
Awake mental replay of past experiences critical for learning
07 May 2012
"Studying tiny bits of genetic material that control protein formation in the brain, Johns Hopkins scientists say that they have new clues to how memories are made and how drugs might someday be used to stop disruptions in the process that lead to mental illness and brain-wasting diseases.
"In a report published in the March 2 issue of Cell, the researchers say that certain microRNAs—genetic elements that control which proteins get made in cells—are the key to controlling the actions of so-called brain-derived neurotrophic factor, or BDNF, long linked to brain cell survival, normal learning and memory boosting."
"How does the brain perceive and interpret beautiful movement?[snip]
"This is one of the key questions being asked by scientists at Bangor University who have enlisted the help of a professional dancer in their quest to better understand how our brains process movement and how we learn by observation.
"Dr Emily Cross' research focuses on the relatively new field of science called neuroaesthetics which looks at how the brain perceives artistic endeavours."
"On 7 March at the Royal Institution in London, Science Weekly presenter Alok Jha will host a debate entitled Consciousness: The Hard Problem?Read the full article and listen to the podcast
"To discuss this slippery subject ahead of the debate Alok brought the three leading researchers and thinkers who will be participating into the Science Weekly studio: Professor Anil Seth, co-director of the Sackler Centre for Consciousness Science at Sussex University; Professor Chris Frith, professor emeritus at the Wellcome Trust Centre for Neuroimaging at University College London; and Dr Barry Smith, director of the Institute of Philosophy at the School of Advanced Study at Birkbeck, University of London."
"Nobel Prize laureate Dr. Stanley Prusiner, who discovered a revolutionary new class of proteins that cause devastating brain diseases in both animals and humans, has become chairman of the scientific advisory board of the Cleveland Clinic Lou Ruvo Center for Brain Health."[snip]
"Its detractors may end up dubbing it "Dementiaville", but Switzerland is brushing aside a debate raging among geriatric-care experts with plans to build a mock-1950s village catering exclusively for elderly sufferers of Alzheimer's and other debilitating mental illnesses."[snip]
"Brain Awareness Week (BAW) is less than two months away (March 12–18) and here at the Dana Foundation we are excited...Remember, the Dana Foundation and the Dana Alliance for Brain Initiatives (DABI) are here to help. If you register your organization with DABI and become a BAW partner at www.dana.org/brainweek/, you’ll get access to free BAW materials. Each year hundreds of BAW partners from Texas to Morocco register events with DABI and receive fun and valuable materials and resources for free."[snip]
"Today, the U.S. Food and Drug Administration allowed marketing of the first test to help determine the risk for a rare brain infection called progressive multifocal leukoencephalopathy (PML) in people using the drug Tysabri (natalizumab) to treat multiple sclerosis (MS) or Crohn’s disease (CD).[snip]
"The Stratify JCV Antibody ELISA test, when used with other clinical data from the patient, can help health care providers determine the risk for developing PML in MS and CD patients."
Four sports organizations will receive $1.5 million in federal funding for new education programs designed to reduce concussions and other brain injuries in children and youth who play team sports.[snip]
The Public Health Agency of Canada's "Active and Safe" program is supporting a joint project of ThinkFirst Canada, the Canadian Centre for Ethics in Sport, the Coaching Association of Canada, and Hockey Canada to help coachers, trainers, parents, and athletes recognize and prevent serious brain injuries.
In announcing the funding in Ottawa Thursday, Minister of State for Amateur Sport Bal Gosal noted that an estimated 90 per cent of severe brain injuries were preventable if parents, coaches and the kids themselves knew more about the risks.
"We can't eliminate all injuries," Gosal said, "but we want to help parents and coaches predict the predictable and prevent what is preventable."