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1.  Anxiety of Alzheimer’s disease patients before and after a standardized on-road driving test 
Background
A large number of licensed elderly drivers are demented or are likely to become demented. On-road driving tests, a method often used to assess driver competency, are likely anxiety-provoking for elderly individuals. This article examines the relationship between anxiety and driving performance in a mildly demented and elderly control (EC) sample.
Methods
Anxiety ratings of fear and tension, as assessed by visual analog scales, of 84 patients clinically diagnosed with mild Alzheimer’s disease (AD) (68 safe/marginal and 16 unsafe drivers) were compared with those of 44 age- and education-equated safe/marginal EC participants, both before and after a standardized on-road driving test.
Results
Analyses revealed significant positive correlations between AD patients’ pre–road test and post–road test tension and post–road test fear ratings and total road test score. Subsequent analyses of variance showed no significant pre–road test differences in fear ratings between the three groups but significantly higher levels of tension among the unsafe AD participants. After adjusting for baseline group differences, unsafe AD drivers experienced stable or higher anxiety levels after road test, whereas both the EC and safe/marginal AD drivers endorsed a significant reduction in anxiety.
Discussion
Unlike their safe EC and safe AD driver counterparts, unsafe AD patients reported continued elevated levels of fear and tension after the road test. Given these findings, we suggest that the most appropriate time for driving instructors to counsel patients regarding their driving skills might be directly after the road test.
doi:10.1016/j.jalz.2006.10.006
PMCID: PMC3598633  PMID: 19595915
Alzheimer’s disease; Driving; Road test; Anxiety; Visual analog mood scales
2.  Hypotheses on the evolution of hyaluronan: A highly ironic acid 
Glycobiology  2013;23(4):398-411.
Hyaluronan is a high-molecular-weight glycosaminoglycan (GAG) prominent in the extracellular matrix. Emerging relatively late in evolution, it may have evolved to evade immune recognition. Chondroitin is a more ancient GAG and a possible hyaluronan precursor. Epimerization of a 4-hydroxyl in N-acetylgalactosamine in chondroitin to N-acetylglucosamine of hyaluronan is the only structural difference other than chain length between these two polymers. The axial 4-hydroxyl group extends out perpendicular from the equatorial plane of N-acetylgalactosamine in chondroitin. We suspect that this hydroxyl is a prime target for immune recognition. Conversion of a thumbs-up hydroxyl group into a thumbs-down position in the plane of the sugar endows hyaluronan with the ability to avoid immune recognition. Chitin is another potential precursor to hyaluronan. But regardless whether of chondroitin or of chitin origin, an ancient chondroitinase enzyme sequence seems to have been commandeered to catalyze the cleavage of the new hyaluronan substrate. The evolution of six hyaluronidase-like sequences in the human genome from a single chondroitinase as found in Caenorhabditis elegans can now be traced. Confirming our previous predictions, two duplication events occurred, with three hyaluronidase-like sequences occurring in the genome of Ciona intestinalis (sea squirt), the earliest known chordate. This was probably followed by en masse duplication, with six such genes present in the genome of zebra fish onwards. These events occurred, however, much earlier than predicted. It is also apparent on an evolutionary time scale that in several species, this gene family is continuing to evolve.
doi:10.1093/glycob/cws218
PMCID: PMC3581078  PMID: 23315448
chondroitin; evolution; hyaluronan; hyaluronidase; immunology
3.  Long Term Consequences: Effects on Normal Development Profile after Concussion 
Each year in the United States, approximately 1.7 million people are diagnosed with a traumatic brain injury (TBI); an estimated 75% of these injuries are classified as mild TBIs (mTBI) or concussions. The symptoms of such injuries include a variety of somatic, cognitive, and behavioral deficits. While these symptoms typically resolve in a matter of weeks, both children and adults may suffer from Post-Concussion Syndrome (PCS) for months or longer. Suffering from PCS-related symptoms for an extended time may delay an individual’s return to work, adversely affect one’s quality of life, and result in additional social and economic costs. Though a consensus has not been reached on the cause of long-term PCS, it is likely that biological, physiological, psychological, and social elements all play a role in symptom persistence. Additionally, persistent PCS may adversely affect one’s developmental trajectory. The enduring effects of head trauma are not limited to PCS-related effects, however. A progressive tauopathy, chronic traumatic encephalopathy (CTE) is believed to stem from repeated brain trauma. While CTE was originally associated with boxing, it has recently been found in other cases of repetitive head injury including former football and hockey players, and professional wrestlers. In addition to this observed pathology, repetitive brain trauma is also associated with Alzheimer’s-like dementia, Parkinsonism, and motor neuron disease including Amyotrophic Lateral Sclerosis (ALS). With these significant long-term effects of head injuries, there is a clear need to develop effective diagnoses, treatments, and education plans to reduce future burden and incidence.
doi:10.1016/j.pmr.2011.08.009
PMCID: PMC3208826  PMID: 22050943
concussion; development; chronic traumatic encephalopathy; postconcussion syndrome; youth
4.  Driving Scenes test of the Neuropsychological Assessment Battery (NAB) and on-road driving performance in aging and very mild dementia 
The Driving Scenes test of the new Neuropsychological Assessment Battery (NAB; [Stern, R.A., & White, T. (2003a). Neuropsychological Assessment Battery. Lutz, FL: Psychological Assessment Resources, Inc.]) measures several aspects of visual attention thought to be important for driving ability. The current study examined the relationship between scores on the Driving Scenes test and on-road driving performance on a standardized driving test. Healthy participants performed significantly better on the Driving Scenes test than did very mildly demented participants. A correlation of 0.55 was found between the brief, office-based Driving Scenes test and the 108-point on-road driving score. Furthermore, the Driving Scenes test scores differed significantly across the driving instructor’s three global ratings (safe, marginal, and unsafe), and results of a discriminant function analysis indicated that the Driving Scenes test correctly classified 66% of participants into these groups. Thus, the new NAB Driving Scenes test appears to have good ecological validity for real-world driving ability in normal and very mildly demented older adults.
doi:10.1016/j.acn.2004.06.003
PMCID: PMC3292213  PMID: 15708731
Driving; Aging; Dementia; Neuropsychology; Attention; Visual
5.  Helmets and Mouth Guards: The Role of Personal Equipment in Preventing Sport-Related Concussions 
Clinics in sports medicine  2011;30(1):145-163.
Every year, millions of athletes in the United States experience concussions. With athletes at all levels of play getting bigger, faster, and stronger, it has been suggested that newer technologies may provide an opportunity to reduce the risk and severity of these all too frequent injuries. Although helmets have been shown to decrease the rate of catastrophic head injuries, and mouth guards have decreased the risk of dental and oral injuries, the protective effect of helmets and mouth guards on concussions has not been conclusively demonstrated. In this review, the current literature pertaining to the effect that equipment has on concussions is evaluated. Understanding the role that this equipment plays in preventing concussions is complicated by many factors, such as selection bias in non-randomized studies, variations in playing style, and risk compensation in sports with mandatory protective equipment. At this point, there is little evidence supporting the use of specific helmets or mouth guards to prevent concussions outside of specific sports such as cycling, skiing, and snowboarding. Improving coach and player education about proper concussion management, encouraging neck strengthening exercises, and minimizing high-risk impacts may provide a more fruitful avenue to reduce concussions in sports.
doi:10.1016/j.csm.2010.09.006
PMCID: PMC2987604  PMID: 21074089
concussion; equipment; helmet; headgear; mouth guard; face shield; sport
6.  Chronic Traumatic Encephalopathy: A Potential Late Effect of Sport-Related Concussive and Subconcussive Head Trauma1 
Clinics in sports medicine  2011;30(1):179-xi.
Synopsis
Chronic traumatic encephalopathy (CTE) is a form of neurodegeneration that is believed to result from repeated head injuries. Originally termed dementia pugilistica due to its association with boxing, the neuropathology of CTE was first described by Corsellis in 1973 in a case series of 15 retired boxers. CTE has recently been found to occur following other causes of repeated head trauma, suggesting that any repeated blows to the head, such as those that occur due to American football, hockey, soccer, professional wrestling, and physical abuse, can also lead to neurodegenerative changes. These changes often include cerebral atrophy, cavum septum pellucidum with fenestrations, shrinkage of the mammillary bodies, dense tau immunoreactive inclusions (neurofibrillary tangles, glial tangles, and neuropil neurites), diffuse axonal injury, and, in some cases, a TDP-43 proteinopathy. In association with these pathological changes, affected individuals often exhibit disordered memory and executive functioning, behavioral and personality disturbances (e.g., apathy, depression, irritability, impulsiveness, suicidality), parkinsonism, and, occasionally, motor neuron disease. At the present time, there are no formal clinical or pathological diagnostic criteria for CTE, but the distinctive neuropathological profile of the disorder lends promise for future research into its prevention, diagnosis, and treatment.
doi:10.1016/j.csm.2010.09.007
PMCID: PMC2995699  PMID: 21074091
Encephalopathy; Post-Traumatic; Neurodegenerative Disorders; Concussion; Athletic Injuries; Dementia; Motor Neuron Disease
7.  Chain Gangs: New Aspects of Hyaluronan Metabolism 
Hyaluronan is a matrix polymer prominent in tissues undergoing rapid growth, development, and repair, in embryology and during malignant progression. It reaches 107 Daltons in size but also exists in fragmented forms with size-specific actions. It has intracellular forms whose functions are less well known. Hyaluronan occurs in all vertebrate tissues with 50% present in skin. Hyaluronan provides a scaffold on which sulfated proteoglycans and matrix proteins are organized. These supramolecular structures are able to entrap water and ions to provide tissues with hydration and turgor. Hyaluronan is recognized by membrane receptors that trigger intracellular signaling pathways regulating proliferation, migration, and differentiation. Cell responses are often dependent on polymer size. Catabolic turnover occurs by hyaluronidases and by free radicals, though proportions between these have not been determined. New aspects of hyaluronan biology have recently become realized: involvement in autophagy, in the pathology of diabetes., the ability to modulate immune responses through effects on T regulatory cells and, in its fragmented forms, by being able to engage several toll-like receptors. It is also apparent that hyaluronan synthases and hyaluronidases are regulated at many more levels than previously realized, and that the several hyaluronidases have functions in addition to their enzymatic activities.
doi:10.1155/2012/893947
PMCID: PMC3246691  PMID: 22216413
8.  Mild traumatic brain injury: a risk factor for neurodegeneration 
Recently, it has become clear that head trauma can lead to a progressive neurodegeneration known as chronic traumatic encephalopathy. Although the medical literature also implicates head trauma as a risk factor for Alzheimer's disease, these findings are predominantly based on clinical diagnostic criteria that lack specificity. The dementia that follows head injuries or repetitive mild trauma may be caused by chronic traumatic encephalopathy, alone or in conjunction with other neurodegenerations (for example, Alzheimer's disease). Prospective longitudinal studies of head-injured individuals, with neuropathological verification, will not only improve understanding of head trauma as a risk factor for dementia but will also enhance treatment and prevention of a variety of neurodegenerative diseases.
doi:10.1186/alzrt42
PMCID: PMC2919698  PMID: 20587081
9.  Thyroid Hormone Levels in the Prefrontal Cortex of Post-Mortem Brains of Alzheimer’s Disease Patients 
Current aging science  2008;1(3):175-181.
Converging evidence suggests a possible link between thyroid state and Alzheimer’s disease (AD), including a higher probability of dementia in individuals with higher TSH levels and a two-fold risk of AD in patients with hypothyroidism. Thyroid hormones modulate factors associated with AD, including amyloid precursor protein expression in the brain, suggesting a possible role for thyroid hormone in AD pathology. The present study is the first to directly evaluate brain thyroid hormone levels in AD. Triiodothyronine (T3) and thyroxine (T4) levels were measured with radioimmunoassay (RIA) in post-mortem samples of prefrontal cortex of patients with pathologically confirmed AD, including Braak stage I–II (n=8), Braak stage V–VI (n=8), and controls without any primary neurological disease (n=8). T4 levels did not differ between groups. T3 levels were significantly lower in Braak stage V–VI brains relative to controls, but there was no statistically significant difference between T3 levels in Braak stage I–II versus controls. Results suggest that the conversion of T4 to T3 may be affected in advanced AD, perhaps due to alterations in deiodinase activity. Reduced conversion of T4 to T3 in AD may be associated with both AD pathology and the clinical presentation of dementia.
PMCID: PMC2953721  PMID: 20021390
Thyroid hormones; thyroxine; Alzheimer’s disease; dementia
10.  TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy 
Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43 kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43–positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.
doi:10.1097/NEN.0b013e3181ee7d85
PMCID: PMC2951281  PMID: 20720505
Amyotrophic lateral sclerosis; Chronic brain injury; Motor neuron disease; Sports; Tau proteins; TDP-43
11.  Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy following Repetitive Head Injury 
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed “dementia pugilistica” and more recently, chronic traumatic encephalopathy (CTE). We review the 47 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professional athletes: one football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, Parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular, patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. CTE is a neuropathologically distinct, slowly progressive tauopathy with a clear environmental etiology.
doi:10.1097/NEN.0b013e3181a9d503
PMCID: PMC2945234  PMID: 19535999
Athletes; Concussion; Dementia; Encephalopathy; Neurodegeneration; Tau protein; Traumatic brain injury
12.  Clock Drawing Test Ratings by Dementia Specialists: Interrater Reliability and Diagnostic Accuracy 
The authors aim to study subjective ratings of clock drawing test by clinicians and determine interrater reliability and diagnostic accuracy. The clock drawing test has been advocated over the Mini-Mental State Examination as an office screening test for dementia, but use of the clock drawing test by neurologists and dementia specialist clinicians has not been validated. The authors conducted a study of clock drawing test scoring by dementia specialists. The authors randomly assigned 25 clocks from each of six predetermined groups based on consensus diagnosis (cognitive comparison subjects, subjects with a memory complaint but with normal neuropsychological testing, subjects with probable and possible mild cognitive impairment, and subjects with possible and probable Alzheimer’s disease) to dementia specialists for blinded scoring using a binary yes/no impairment system and a 0–10 scale as subjectively determined by each individual clinician rater. The authors collapsed the six groups into three (comparison subjects, mild cognitive impairment patients, and Alzheimer’s disease patients) and analyzed interrater reliability, sensitivity, and specificity for consensus diagnosis of mild cognitive impairment, and Alzheimer’s disease. The authors found excellent interrater reliability, sensitivity, and specificity for predicting consensus diagnosis. The 0–10 clock drawing test rating scale was more predictive of consensus diagnosis than the binary impairment scale. Based on the five clinicians’ average dichotomous rating, the clinicians differentiated comparison and Alzheimer’s disease participants with a sensitivity of 0.75 and a specificity of 0.81. For three of the four comparisons, a cutoff score of two or greater resulted in the maximization of sensitivity and specificity for differentiating diagnostic groups. A cutoff score of four or greater maximized sensitivity (0.54) and specificity (0.74) for differentiating Alzheimer’s disease from mild cognitive impairment. Based on rating systems, clock drawing test scoring by dementia clinicians had excellent interrater reliability and sensitivity for differentiating the mild Alzheimer’s disease subjects from comparison subjects. When utilizing a binary rating scale for the clock drawing test in the absence of clinical information, dementia specialist clinicians at the Boston Medical Center were moderately sensitive and highly specific in separating mild cognitive impairment from healthy comparison subjects. These dementia clinicians were also highly sensitive and less specific in differentiating mild cognitive impairment from Alzheimer’s disease.
doi:10.1176/appi.neuropsych.22.1.85
PMCID: PMC2938787  PMID: 20160214
13.  Predicting cognitive decline and conversion to Alzheimer's disease in older adults using the NAB List Learning test 
To validate the Neuropsychological Assessment Battery (NAB) List Learning test as a predictor of future multi-domain cognitive decline and conversion to Alzheimer's disease (AD), participants from a longitudinal research registry at a national AD Center were, at baseline, assigned to one of three groups (control, mild cognitive impairment [MCI], or AD), based solely on a diagnostic algorithm for the NAB List Learning test (Gavett et al., 2009), and followed for 1–3 years. Rate of change on common neuropsychological tests and time to convert to a consensus diagnosis of AD were evaluated to test the hypothesis that these outcomes would differ between groups (AD>MCI>control). Hypotheses were tested using linear regression models (n = 251) and Cox proportional hazards models (n = 265). The AD group declined significantly more rapidly than controls on Mini-Mental Status Examination (MMSE), animal fluency, and Digit Symbol; and more rapidly than the MCI group on MMSE and Hooper Visual Organization Test. The MCI group declined more rapidly than controls on animal fluency and CERAD Trial 3. The MCI and AD groups had significantly shorter time to conversion to a consensus diagnosis of AD than controls. The predictive validity of the NAB List Learning algorithm makes it a clinically useful tool for the assessment of older adults.
doi:10.1017/S1355617710000421
PMCID: PMC2922010  PMID: 20374677
Memory; Dementia; Differential diagnosis; Aging; Neuropsychology; Neuropsychological tests
14.  A Questionnaire for the Assessment of the Multiple Dimensions of Motion Sickness 
Background
A limited number of attempts have been made to develop a questionnaire that assesses the experience of motion sickness. Further, many available questionnaires quantify motion sickness as a unidimensional construct
Method
Exploratory and confirmatory factor analyses of motion sickness descriptors were used to derive and verify four dimensions of motion sickness, which were defined as gastrointestinal, central, peripheral, and sopite-related. These dimensions of motion sickness were then used to construct a motion sickness assessment questionnaire (MSAQ) that was administered to individuals who were exposed to a rotating optokinetic drum.
Results
Total scores from the MSAQ correlated strongly with overall scores from the Pensacola Diagnostic index (r = 0.81, p < 0.001) and the Nausea Profile (r = 0.92, p < 0.001).
Conclusions
The MSAQ is a valid instrument for the assessment of motion sickness. In addition, the MSAQ may be used to assess motion sickness as a multidimensional rather than unidimensional construct
PMCID: PMC2910410  PMID: 11211039
factor analysis; motion sickness; questionnaire
15.  Relationship of gastric myoelectrical and cardiac parasympathetic activity to chemotherapy-induced nausea 
Journal of psychosomatic research  2001;50(5):263-266.
Objectives
We evaluated (a) whether pretreatment levels of gastric tachyarrhythmia, a dysrhythmic pattern of gastric myoelectrical activity, or cardiac parasympathetic activity are associated with the development of chemotherapy-induced nausea and (b) whether chemotherapy-induced nausea is preceded by an increase in gastric tachyarrhythmia and a decrease in cardiac parasympathetic activity, as has been observed during motion sickness.
Methods
Electrogastrograms and estimates of respiratory sinus arrhythmia (RSA) were obtained from cancer chemotherapy patients before treatment and for approximately 24 hours after treatment.
Results
Higher levels of pretreatment gastric tachyarrhythmia were observed on chemotherapy sessions that were followed by posttreatment reports of nausea. Pretreatment levels of RSA, however, did not differ between chemotherapy treatments that were and were not followed by nausea. No statistically significant changes in gastric tachyarrhythmia or RSA were observed prior to first reports of nausea following chemotherapy.
Conclusions
In contrast to motion sickness, chemotherapy-induced nausea may not be related to an increase in dysrhythmic gastric myoelectrical activity; however, higher levels of pretreatment gastric tachyarrhythmia may be related to posttreatment reports of chemotherapy-induced nausea.
PMCID: PMC2904503  PMID: 11399283
Cancer chemotherapy; Electrogastrography; Gastric tachyarrhythmia; Nausea; Parasympathetic
16.  Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors 
Psychophysiology  2001;38(4):642-652.
We evaluated the effects of two laboratory stressors (speech preparation and isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and the extent to which autonomic responses to these stressors and somatization predict reports of motion sickness during exposure to a rotating optokinetic drum. Both stressors prompted a decrease in preejection period (PEP) and respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced decreases in RSA and higher somatization scores predicted increased reports of motion sickness during drum rotation. These results demonstrate that laboratory stressors concurrently affect gastric myoelectrical activity and autonomic control of the heart, and that stressor-induced decreases in RSA and higher levels of somatization predict motion sickness susceptibility.
PMCID: PMC2904511  PMID: 11446577
Electrogastrography; Impedance cardiography; Motion sickness; Parasympathetic; Somatization; Stress; Sympathetic
17.  Relationship between temporal changes in cardiac parasympathetic activity and motion sickness severity 
Psychophysiology  2003;40(1):39-44.
Chemotherapy-induced nausea has been associated with a time-related decrease in cardiac parasympathetic activity. We tested the hypothesis that a time-related decrease in cardiac parasympathetic activity would also be associated with nausea and other motion sickness symptoms during illusory self-motion (vection). Fifty-nine participants (aged 18–34 years: 25 male) were exposed to a rotating optokinetic drum to induce vection. Symptoms of motion sickness and an estimate of cardiac parasympathetic activity (respiratory sinus arrhythmia; RSA) were obtained at baseline and throughout a drum-rotation period. As expected, motion sickness symptoms increased and RSA decreased over time during drum rotation.Moreover, greater decreases in RSA over time correlated with greater motion sickness severity. These results suggest that a time-related decrease in cardiac parasympathetic activity may be an important correlate of nausea and motion sickness across different evocative contexts.
PMCID: PMC2901547  PMID: 12751802
Individual differences; Motion sickness; Nausea; Parasympathetic; Respiratory sinus arrhythmia; Time
18.  Lower-Extremity Function in Cognitively Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease 
Objective
To examine differences in lower-extremity function in cognitive healthy older persons, older persons with mild cognitive impairment (MCI), and older persons with Alzheimer’s disease (AD).
Design
Descriptive study.
Setting
University Alzheimer’s disease clinical and research program.
Participants
Older persons (N=66) were studied (mean age, 76.7y); 22 were cognitively normal, 22 were diagnosed with probable MCI, 22 were diagnosed with probable AD.
Interventions
Not applicable.
Main Outcome Measures
Lower-extremity function was assessed by the four-meter walk test (4MWT), Timed Up & Go (TUG) test, and sit-to-stand (STS) test.
Results
Analysis of variance, adjusting for covariates, revealed that performance on the 4MWT was significantly lower in the MCI and AD groups as compared with controls. TUG test performance was worse in the AD group compared with controls. No significant group differences were found for STS performance.
Conclusions
These results suggest an association between cognitive impairment and lower-limb function in older persons Walking speed could be evaluated for its possible utility in screening older persons at risk for cognitive impairment and falls.
doi:10.1016/j.apmr.2009.11.020
PMCID: PMC2864645  PMID: 20382291
Aging; Alzheimer disease; Cognition; Gait; Rehabilitation
19.  A New Scale Measuring Psychological Impact of Genetic Susceptibility Testing for Alzheimer’s Disease 
This paper describes the development and psychometric properties of a new scale for assessing the psychological impact of genetic susceptibility testing for Alzheimer’s disease (AD). The new instrument, The REVEAL Impact of Genetic Testing for Alzheimer’s disease (IGT-AD) was designed to examine the unique nature of genetic information and the disease course of AD. The scale was tested as a part of a multicenter clinical trial designed to evaluate the impact of AD risk assessment and data was collected from 276 participants in the study. Using an iterative process of Principal Component Analysis and Cronbach’s alpha, the final 16 item IGT-AD was found to have a two factor structure with excellent internal reliability. Construct validity was established by patterns of correlation with other standardized self-reported measures. This scale should be useful in the identification of patients who maybe susceptible to the negative effects of receiving genetic information, monitoring of patients who have received genetic information, and as a tool for researchers who wish to study the effects of genetic susceptibility testing for AD.
PMCID: PMC2743905  PMID: 19266699
Alzheimer’s disease genetics; genetic testing; Alzheimer’s disease risk assessment
20.  Clock Drawing Performance in Cognitively Normal Elderly 
The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems (Mendez, Ala, and Underwood, 1992; Freund, Gravenstein, Ferris, Burke, & Shaheen, 2005; and Cahn, Salmon, Monsch, Butters, Wiederholt, & Corey-Bloom, 1996), among 207 cognitively normal elderly. The systems were well correlated, took little time to use, and had high inter-rater reliability. We found statistically significant differences in CDT scores based on age and WRAT-3 Reading score, a marker of education quality. We present means, standard deviations, and t- and z-scores based on these subgroups. We found that “normal” CDT performance includes a wider distribution of scores than previously reported. Our results may serve as useful comparisons for clinicians wishing to know whether their patients perform in the general range of cognitively normal elderly.
doi:10.1016/j.acn.2007.12.003
PMCID: PMC2752157  PMID: 18243644
Clock Drawing Test; clock drawing; normal aging; normative data; scoring systems; neuropsychological tests; elderly; Alzheimer’s disease; mild cognitive impairment; dementia; cognitive decline; cognitive screening
21.  Cognitive correlates of HVOT performance differ between individuals with mild cognitive impairment and normal controls 
Objective
To clinically characterize performance on the Hooper Visual Organization Test (HVOT) among participants with mild cognitive impairment (MCI) and to identify naming and executive functioning correlates associated with HVOT performance among MCI participants and normal controls (NC).
Background
The HVOT is a common neuropsychological instrument that measures visuospatial skills and agnosia. It has, however, been criticized for its multifactorial nature, as several studies have reported executive or language correlates of HVOT performance. To our knowledge, simultaneous comparison of executive functioning and language demands of the HVOT has never been performed among an older cohort.
Methods
The HVOT, two tests of executive functioning [Trail Making Test, Part B (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222 NC, 166 MCI, and 68 Alzheimer’s disease (AD) individuals.
Results
HVOT scores were significantly different between all three groups in the expected direction (AD < MCI < NC). Linear regression among NC participants revealed that COWA, age, and BNT were significantly associated with HVOT scores, accounting for 12%, 6%, and 4% of HVOT variance, respectively. Among MCI participants, the BNT accounted for 43% of HVOT variance. Neither TMT-B nor Animal Naming was a significant predictor for either group.
Conclusion
Among NC participants, rapid word generation (i.e., COWA), a measure of executive functioning, is the most salient predictor of HVOT performance. In contrast, lexical retrieval (i.e., BNT) is the most salient language or executive functioning predictor of HVOT performance among MCI participants. These findings extend previous claims that the HVOT is multifactorial by suggesting that reduced HVOT performance in MCI patients may be related to mild lexical retrieval impairments.
doi:10.1016/j.acn.2006.06.001
PMCID: PMC2746420  PMID: 16893623
Object recognition; Mild cognitive impairment; Hooper Visual Organization Test
22.  Geriatric Performance on an Abbreviated Version of the Boston Naming Test 
Applied neuropsychology  2007;14(3):215-223.
Abbreviated neuropsychological protocols are increasingly utilized secondary to time-constraints within research and healthcare settings, yet normative data for these abbreviated instruments are lacking. We present geriatric performances and normative data for the Boston Naming Test 30-item even verion (BNT-30). Data were utilized from the BU-ADCC registry (n = 441, ages 55-98) and included 219 normal controls (NC), 155 participants with mild cognitive impairment (MCI), and 67 participants with Alzheimer’s disease (AD). The NC group (M = 28.7, SD = 1.8) significantly outperformed both MCI (M = 26.2, SD = 4.4) and AD (M = 22.1, SD = 4.8) groups, and the MCI group outperformed the AD group. Normative data generated for the NC participants revealed a significant between-group difference for sex (males M = 29.1, SD = 1.7; females M = 28.4, SD = 1.8) and race (White M = 28.8, SD = 1.7; African American M = 27.5, SD = 2.1). The racial disparity remained even after adjusting for education level (p = .002) and literacy (p < .001). ANOVAs for the NC group were non-significant for age but significant for education level (p = .001). Geriatric normative data therefore suggest that sex, race, and education are all associated with naming performance, and these variables should be taken into consideration when interpreting geriatric BNT-30 performance.
doi:10.1080/09084280701509166
PMCID: PMC2741691  PMID: 17848132
Alzheimer’s disease; Boston Naming Test; geriatrics; language; lexical retrieval; mild cognitive impairment; neuropsychological measures; normative data
23.  Test–retest stability on the WRAT-3 reading subtest in geriatric cognitive evaluations 
The primary goal of this study was to establish the stability of the Wide Range Achievement Test (WRAT-3) Reading score across two annual assessments of aging individuals. Participants were classified as controls (n = 200), mild cognitive impairment (MCI; n = 137), or possible or probable Alzheimer’s disease (AD; n = 41). Test–retest stability was acceptable to high for all diagnostic groups. The descriptive classification (e.g., “average”) remained consistent for only 74% of participants. Results indicated that WRAT-3 Reading scores are appropriate for use with older adults, though the use of categorical descriptors to describe premorbid ability based on these scores is not supported.
doi:10.1080/13803390802375557
PMCID: PMC2728046  PMID: 18821160
Wide Range Achievement Test–Third Edition; Reading; Literacy; Test–retest; Geriatrics; Mild cognitive impairment; Alzheimer’s disease

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