Neurostimulation for cognitive enhancement in Alzheimer’s disease (the NICE-AD study): a randomized clinical trial

New therapies for symptoms in Alzheimer’s disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. This study has been registered on www.Clinicaltrials.gov - identifier: NCT 04404153 .

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Predictors of Life Expectancy After an Alzheimer’s Disease Diagnosis in a National Multi-Center Autopsy-Confirmed Sample

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz035.13 ◽

2019 ◽

Vol 34 (6) ◽

pp. 845-845

Author(s):

J Schaffert ◽

C LoBue ◽

C Presley ◽

L Hynan ◽

K Wilmoth ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Life Expectancy ◽

Psychiatric Symptoms ◽

Significant Proportion ◽

Disease Diagnosis ◽

Small Sample ◽

Clinical Diagnoses ◽

Race Ethnicity ◽

Small Sample Sizes

Abstract Objective Life expectancy varies between 3-12 years following the diagnosis of Alzheimer’s disease (AD) and is an important clinical question for patients and families. Current literature is limited by relatively small sample sizes and a reliance on clinical diagnoses. This study sought to evaluate predictors of AD life expectancy in a large autopsy-confirmed sample. Methods Baseline data from individuals 50 years and older clinically and neuropathologically diagnosed with AD (N=764) were obtained from the National Alzheimer’s Coordinating Center. Life expectancy was calculated in months from AD diagnosis to death. Nineteen variables (demographic, medical/health, disease severity, and psychiatric) obtained at dementia diagnosis were examined. Variables that showed significant differences in life expectancy using t-tests and Pearson correlations (14 of 19) were then entered into a forward multiple regression. Results Seven predictors in the model explained 27% of the variance in life expectancy (F= 40.7, R-squared= 0.267). Lower MMSE scores (β= 0.339, p < .001), male sex (β= -0.144, p < .001), older age (β= -0.130, p < .001), non-Hispanic Caucasian race/ethnicity (β= 0.115, p < .001), greater impairment on the Functional Activities Questionnaire (β= -0.091, p=.042), abnormal neurological/physical exam (β= -0.083, p=.011), and higher Neuropsychiatric Inventory Questionnaire total scores (β= -0.079, p=.016) predicted shorter life expectancy. Conclusions Global cognitive impairment, sex, age, race/ethnicity, functional impairment, abnormal neurological exam findings, and psychiatric symptoms explain a significant proportion of life expectancy following an AD diagnosis. Future studies should explore the relationship between life expectancy, specific neurological abnormalities, and psychiatric symptoms. These 7 predictors could potentially be used to predict life expectancy in individuals diagnosed with AD.

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VITAMIN D AND DEMENTIA

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2015.68 ◽

2015 ◽

pp. 1-10

Author(s):

T.J. Littlejohns ◽

K. Kos ◽

W.E. Henley ◽

E. Kuma ◽

D.J. Llewellyn

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vitamin D ◽

Longitudinal Studies ◽

Ventricular Volume ◽

Vitamin D Supplementation ◽

Small Sample ◽

Double Blind ◽

Cross Sectional ◽

Increased Risk

Emerging evidence suggests that low vitamin D concentrations are potentially involved in the pathogenesis of dementia. This is of particular interest when considering the high prevalence of vitamin D deficiency in elderly adults and the urgent need to identify modifiable risk factors for dementia. Studies have found that vitamin D is implicated in procognitive and neuroprotective functions, including the reduction of Alzheimer’s disease hallmarks such as amyloid beta and phosphorylated tau. Cross-sectional studies have consistently found that vitamin D concentrations are significantly lower in individuals with Alzheimer’s disease and cognitive impairment compared to healthy controls. Longitudinal studies support an association between low vitamin D concentrations and an increased risk of dementia and cognitive decline. Neuroimaging studies are beginning to uncover the potential neurodegenerative and cerebrovascular mechanisms that underlie these associations such as white matter hyperintensities and enlarged ventricular volume, although there is currently a lack of longitudinal studies. In contrast to observational studies, findings from interventional studies have produced mixed results on the benefits of vitamin D supplementation on dementia and cognitive outcomes. Interpretation of the findings from these studies is hampered by several major methodological limitations, such as small sample sizes, inadequate doses and inclusion of participants unlikely to benefit from vitamin D supplementation. There is a need for large double-blind randomised-control trials investigating whether vitamin D supplementation can halt or delay the risk of dementia-related outcomes in individuals with low vitamin D concentrations.

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Psychosis in Alzheimer's Disease in the National Alzheimer's Disease Coordinating Center Uniform Data Set: Clinical Correlates and Association with Apolipoprotein E

International Journal of Alzheimer s Disease ◽

10.4061/2011/926597 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Mary Ann A. DeMichele-Sweet ◽

Oscar L. Lopez ◽

Robert A. Sweet

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Late Onset ◽

Small Sample ◽

Carrier Status ◽

Data Set ◽

Allele Number ◽

Heritable Phenotype ◽

Small Sample Sizes

Approximately 50% of late-onset Alzheimer's disease (AD) patients develop psychosis (AD+P), a heritable phenotype associated with more rapid cognitive decline. Prior studies conflict regarding whether apolipoprotein E (APOE) ϵ4 alleles are associated with AD+P, possibly due to small sample sizes, inconsistent diagnostic criteria, and different methodologies to assess psychosis. We used the National Alzheimer's Coordinating Center Uniform Data Set to evaluate the largest uniformly characterized sample of AD+P subjects studied to date for the association of APOE ϵ4 genotype, along with other demographic and clinical variables. Greater cognitive impairment and depressive symptoms were associated with AD+P, while the Caucasian race was protective. Neither APOE ϵ4 carrier status nor allele number was associated with psychosis. The AD+P phenotype is not associated with the APOE ϵ4 genotype. AD+P may represent a useful phenotype for the discovery of non-APOE ϵ4 genetic variation contributing to the risk of AD.

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Case Studies in Dementia-Related Anxiety

GeroPsych ◽

10.1024/1662-9647/a000243 ◽

2020 ◽

pp. 1-6

Author(s):

Molly Maxfield ◽

Jennifer R. Roberts ◽

JoAnna Dieker

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Social Withdrawal ◽

Cognitive Status ◽

Generalized Anxiety ◽

Neurocognitive Disorder ◽

High Genetic Risk ◽

Disease Case ◽

Negative Perceptions

Abstract. Two clients seeking neuropsychological assessment reported anxiety about their cognitive status. We review the cases to increase our understanding of factors contributing to dementia-related anxiety. Case 1 met the criteria for mild neurocognitive disorder; the client’s memory was impaired, and she had a high genetic risk for Alzheimer’s disease. The client reported anxiety about negative perceptions of quality of life among individuals diagnosed with Alzheimer’s disease. Case 2 did not meet the criteria for a neurocognitive disorder. Anxiety about this client’s cognitive status appeared attributable to generalized anxiety disorder, given his anxiety about diverse topics. Both clients reported embarrassment about forgetfulness and social withdrawal. Dementia-related anxiety is believed to be relatively common, to exist on a continuum, to have unique social implications, and to stem from various sources, necessitating differing interventions.

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Validación de la escala Quality of Life in Alzheimer’s Disease (QOL-AD) en pacientes mexicanos con demencia tipo Alzheimer, vascular y mixta

Revista de Neurología ◽

10.33588/rn.5102.2009648 ◽

2010 ◽

Vol 51 (02) ◽

pp. 72 ◽

Cited By ~ 3

Author(s):

Oscar Rosas Carrasco ◽

Laura del Pilar Torres Arreola ◽

María de Guadalupe Guerra Silla ◽

Sara Torres Castro ◽

Luis Miguel Gutiérrez Robledo

Keyword(s):

Quality Of Life ◽

Alzheimer’S Disease ◽

Alzheimer's Disease

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No Evidence that Experiencing Physical Warmth Promotes Interpersonal Warmth: Two Failures to Replicate Williams and Bargh (2008)

10.31234/osf.io/mvn9b ◽

2018 ◽

Cited By ~ 1

Author(s):

Christopher Chabris ◽

Patrick Ryan Heck ◽

Jaclyn Mandart ◽

Daniel Jacob Benjamin ◽

Daniel J. Simons

Keyword(s):

Null Hypothesis ◽

Small Sample ◽

Sample Sizes ◽

Double Blind ◽

Bayesian Analyses ◽

Physical Warmth ◽

Small Sample Sizes ◽

Interpersonal Warmth

Williams and Bargh (2008) reported that holding a hot cup of coffee caused participants to judge a person’s personality as warmer, and that holding a therapeutic heat pad caused participants to choose rewards for other people rather than for themselves. These experiments featured large effects (r = .28 and .31), small sample sizes (41 and 53 participants), and barely statistically significant results. We attempted to replicate both experiments in field settings with more than triple the sample sizes (128 and 177) and double-blind procedures, but found near-zero effects (r = –.03 and .02). In both cases, Bayesian analyses suggest there is substantially more evidence for the null hypothesis of no effect than for the original physical warmth priming hypothesis.

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