Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Dementia prevention, intervention, and care

Context Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. Objective To evaluate the relationship between gait speed and survival. Design, Setting, and Participants Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34 485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. Main Outcome Measures Survival rates and life expectancy. Results There were 17 528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P  Conclusion In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

https://jamanetwork.com/journals/jama/articlepdf/644554/joc05171_50_58.pdf

Gait speed and survival in older adults.

In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

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Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

/pdf/diagnosis-and-management-of-dementia-with-lewy-bodies-fourth-bauvdvbrlh.pdf

Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium

Lafaille-Magnan et al.1 reported that the association between odor identification deficits and cognition in older adults at increased risk of Alzheimer disease (AD) was driven by the presence of AD-related CSF biomarkers rather than the effects of age or other confounders. In addition, the findings were best explained by CSF tau rather than β-amyloid levels. These findings agree with postmortem observations that neurofibrillary tangles in the mesiotemporal lobe robustly predict olfactory deficits in the elderly.2 Dementia with Lewy bodies (DLB) is the second most common type of dementia; odor identification deficits in this hypodopaminergic disorder tend be more severe than in AD.3 However, tau pathology in DLB is substantially less severe compared to AD, including the mesiotemporal lobe.4

Reader response: Odor identification as a biomarker of preclinical AD in older adults at risk.

/pdf/have-we-been-overestimating-fall-rates-in-parkinson-s-5fe1ozs7hb.pdf

Have we been overestimating fall rates in Parkinson's disease?

We introduce basic concepts of brain networks and discuss methods to model and analyze brain molecular connectivity using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Basic elements of network analytic methods, including graph theory, and the connectivity matrix as a basis for network analysis will be discussed in more detail. Statistical methods to compare networks will be reviewed. A specific brain network analysis method called sparse inverse covariance estimation (SICE) is presented as an alternative to Pearson correlation to estimate the brain molecular connectivity matrix. Finally, we will discuss examples from published research to illustrate the practical application of brain molecular connectivity analysis concepts.

Use of Nuclear Medicine Molecular Neuroimaging to Model Brain Molecular Connectivity

Objective Attentional function deficits secondary to degeneration of brain cholinergic systems are significant contributors to gait-balance deficits in Parkinson disease (PD). As an initial step towards assessing if α4β2* nicotinic acetylcholine receptor (nAChR) stimulation improves attention and gait-balance function, we assessed target engagement of the α4β2* nAChR partial agonist varenicline. Methods Non-demented PD participants with cholinergic deficits were identified with [18F]fluoroethoxybenzamicol positron emission tomography (PET). α4β2* nAChR occupancy after subacute oral varenicline treatment was measured with [18F]flubatine PET. With a dose selected from the receptor occupancy experiment, varenicline effects on gait, balance, and cognition were assessed in a double-masked placebo-controlled crossover study. Primary endpoints were normal pace gait speed and a measure of postural stability. Results All varenicline doses (0.25 mg per day, 0.25 mg b.i.d., 0.5 mg b.i.d., and 1.0 mg b.i.d.) produced 60% - 70% receptor occupancy. We selected 0.5 mg po b.i.d for the crossover study. Thirty-three (of thirty-four) participants, completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved performance on a sustained attention test. We obtained identical conclusions in 28 participants in whom treatment compliance was confirmed by plasma varenicline measurements. Interpretation Varenicline occupied a significant fraction of α4β2* nicotinic acetylcholine receptors, was tolerated well, enhanced attentional function, and altered gait performance. These results are consistent with relevant target engagement. Varenicline or similar agents may be worth further evaluation for mitigation of gait and balance disorders in PD.

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α4β2* Nicotinic Cholinergic Receptor Target Engagement in Parkinson Disease Gait-Balance Disorders

Several measures of balance obtained from quiet stance on an electronic platform are described. These measures were found to discriminate patients with Parkinson disease (PD) from normal control subjects. First degree relatives of patients with PD show greater variability on these measures. A primary goal is to develop sensitive measures that would be capable of identifying impaired balance in early stages of non-clinical PD.

Nicolaas I. Bohnen

Papers

Reader response: Odor identification as a biomarker of preclinical AD in older adults at risk.

Have we been overestimating fall rates in Parkinson's disease?

Use of Nuclear Medicine Molecular Neuroimaging to Model Brain Molecular Connectivity

α4β2* Nicotinic Cholinergic Receptor Target Engagement in Parkinson Disease Gait-Balance Disorders

Electronic platform measures of balance impairment in parkinsonians and first degree relatives.