Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits'

Background/Aim: To explore the theory of ‘growing into deficits', a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH). Methods: Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results: Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30). Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7%) patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion: In our opinion, the theory of ‘growing into deficits' shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis.

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Serum Daytime Melatonin Levels Reflect Cerebrospinal Fluid Melatonin Levels in Alzheimer’s Disease but Are Not Correlated with Cognitive Decline

Journal of Alzheimer s Disease ◽

10.3233/jad-210562 ◽

2021 ◽

pp. 1-12

Author(s):

Amber Nous ◽

Mandy Melissa Jane Wittens ◽

Yannick Vermeiren ◽

Peter Paul De Deyn ◽

Christine Van Broeckhoven ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Healthy Controls ◽

Night Time ◽

Cross Sectional ◽

State Examination

Background: Nocturnal cerebrospinal fluid (CSF) and blood melatonin levels are altered in Alzheimer’s disease (AD). However, literature remains inconclusive on daytime blood melatonin levels. A positive correlation between melatonin levels and Mini-Mental State Examination (MMSE) scores in AD subjects has been evidenced following cross-sectional analyses. Whereas a correlation between serum and spinal CSF melatonin has been shown in healthy volunteers, an equal investigation in AD patients still has to be undertaken. Objective: 1) To evaluate whether serum melatonin levels correlate with spinal CSF melatonin levels in AD. 2) To compare daytime CSF and serum melatonin levels between patients with AD dementia, mild cognitive impairment due to AD, and healthy controls, and to evaluate whether melatonin can affect cognitive decline in AD. Methods: Subjects with AD and healthy controls included in two existing cohorts, of whom a CSF and serum sample was available at the neurobiobank and had at least 6 months of neuropsychological follow-up, were included in the present study. Melatonin concentrations were measured with liquid chromatography-mass spectrometry. Results: Daytime serum melatonin levels correlated with spinal CSF melatonin levels in AD (r = 0.751, p < 0.001). No significant differences regarding daytime melatonin levels were found between patients and controls. No correlations were observed between daytime melatonin levels and MMSE score changes. Conclusion: Daytime serum melatonin accurately reflects CSF melatonin levels in AD, raising the possibility to assess melatonin alterations by solely performing blood sampling if also confirmed for night-time values. However, daytime melatonin levels are not associated with changes of cognitive impairment.

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TOP CITED PAPERS IN INTERNATIONAL PSYCHOGERIATRICS: 6c. TRACKING COGNITIVE DECLINE IN ALZHEIMER'S DISEASE USING THE MINI-MENTAL STATE EXAMINATION: A META-ANALYSIS (“MINI” IS NOT NECESSARILY TRIVIAL!) – ERRATUM

International Psychogeriatrics ◽

10.1017/s1041610209991244 ◽

2009 ◽

Vol 22 (1) ◽

pp. 169-169

Author(s):

Ling Han ◽

David Ames

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Mental State ◽

Mini Mental State Examination ◽

Meta Analysis ◽

State Examination

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Assessing the Progression of Alzheimer’s Disease in Real-World Settings in Three European Countries

Journal of Alzheimer s Disease ◽

10.3233/jad-201172 ◽

2021 ◽

Vol 80 (2) ◽

pp. 749-759

Author(s):

Albert Lladó ◽

Lutz Froelich ◽

Rezaul K. Khandker ◽

Montserrat Roset ◽

Christopher M. Black ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mixed Model ◽

Primary Objective ◽

Community Dwelling ◽

Behavioral Changes ◽

The Uk ◽

State Examination ◽

Study Inclusion

Background: There exists considerable variation in disease progression rates among patients with Alzheimer’s disease (AD). Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. Results: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, ‘not reached’) years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. Conclusion: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.

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Educational bias in the assessment of severe dementia: Brazilian cutoffs for severe Mini-Mental State Examination

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20140002 ◽

2014 ◽

Vol 72 (4) ◽

pp. 273-277 ◽

Cited By ~ 13

Author(s):

José Roberto Wajman ◽

Fabricio Ferreira de Oliveira ◽

Rodrigo Rizek Schultz ◽

Sheilla de Medeiros Correia Marin ◽

Paulo Henrique Ferreira Bertolucci

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mental State ◽

Cognitive Assessment ◽

Mini Mental State Examination ◽

Cognitive Responses ◽

Clinical Dementia Rating ◽

Severe Dementia ◽

Advanced Stages ◽

State Examination

Cognitive assessment in advanced stages of Alzheimer’s disease (AD) is limited by the imprecision of most instruments. Objective: To determine objective cognitive responses in moderate and severe AD patients by way of the Severe Mini-Mental State Examination (SMMSE), and to correlate performances with Mini-Mental State Examination (MMSE) scores. Method: Consecutive outpatients in moderate and severe stages of AD (Clinical Dementia Rating 2.0 or 3.0) were evaluated and compared according to MMSE and SMMSE scores. Results: Overall 400 patients were included, 67.5% females, mean age 76.6±6.7 years-old. There was no significant impact of age or gender over MMSE or SMMSE scores. Mean schooling was 4.4±2.5 years, impacting SMMSE scores (p=0.008). Scores on MMSE and SMMSE were significantly correlated (F-ratio=690.6325, p<0.0001). Conclusion: The SMMSE is influenced by schooling, but not by age or gender, and is an accurate test for assessment of moderate and severe AD.

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Smell identification test as a progression marker in Alzheimer's disease

European Psychiatry ◽

10.1016/s0924-9338(11)72209-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 502-502

Author(s):

L. Velayudhan ◽

M. Pritchard ◽

S. Lovestone

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Late Onset ◽

Linear Regression Analysis ◽

Rapid Progressors ◽

Progression Marker ◽

Identification Test ◽

Smell Identification

IntroductionFactors influencing or predicting progression in Alzheimer's disease (AD) is not well understood. Olfactory dysfunction, impaired smell identification in particular, is known to occur in AD. Mesial temporal lobe, important for memory function is also critical for the processing of olfactory information. In view of the common anatomical substrate, we hypothesized that olfaction dysfunction worsens faster in people with AD with rapid cognitive decline compared to those with slower cognitive decline.AimsTo test whether smell identification test can be used as a predictor for illness progression in AD patients.MethodsForty one participants with late onset mild to moderate AD were recruited from mental health services for older adults. Subjects were classified as ‘Rapid Progressors’ defined on ‘a-priori’ with a loss of 2 or more points in Mini-Mental State Examination (MMSE) within six months. Assessments included MMSE, Neuropsychiatric Inventory, Bristol Activities of Daily Living, and the University of Pennsylvania Smell Identification Test (UPSIT), at baseline and after 3 months.ResultsTwenty subjects were ‘Rapid Progressors’, and had lower UPSIT scores compared to ‘Non-Rapid Progressors’ both at the baseline (p = 0.02) and at follow up after 3 months (p = 0.05). Baseline UPSIT correlated with follow up UPSIT (r = 0.5, p < 0.01) and MMSE (r = 0.4, p = 0.04). Also it was the baseline UPSIT score that best predicted (p < 0.05) the follow up smell and cognitive function on linear regression analysis.ConclusionsSmell identification function could be useful as a clinical measure to assess and predict progression in AD.

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IC-P-134: Differentiating Preclinical Alzheimer’s Disease from Normal Aging: The Effects of Age and Amyloid on Cognitive Decline Over 3.5 Years

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.164 ◽

2016 ◽

Vol 12 ◽

pp. P100-P100

Author(s):

Michelle E. Farrell ◽

Kristen M. Kennedy ◽

Karen M. Rodrigue ◽

Gagan S. Wig ◽

Gérard N. Bischof ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Normal Aging ◽

Preclinical Alzheimer’S Disease

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Anticholinergics and Benzodiazepines on Cognitive Impairment among Elderly with Alzheimer’s Disease: a One year Follow-Up Study

10.21203/rs.2.17956/v1 ◽

2019 ◽

Author(s):

Rewadee Jenraumjit ◽

Surarong Chinwong ◽

Dujrudee Chinwong ◽

Tipaporn Kanjanarach ◽

Thanat Kshetradat ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Psychological Symptoms ◽

Esterase Inhibitors ◽

One Year ◽

State Examination ◽

Harmful Effects

Abstract Objective Age-associated decline in central cholinergic activity makes older adults susceptible to harmful effects of anticholinergics (ACs). Evidence exists of an association between effects of AC medications on cognition. This retrospective cohort study examines how ACs affect cognition among older adults with Alzheimer’s disease (AD) who received acetylcholine esterase inhibitors (AChEIs) over the course of 12 months. Results A total of 133 (80% women, mean age 78.38 years, SD 7.4) were recruited. No difference in sex, age and comorbid diseases was observed between participants who took ACs, Benzodiazepines (BZDs) and AChEIs. The most common prescribed ACs was quetiapine, being used for behavioral and psychological symptoms (BPSD). Multilevel analysis showed that the change of mental state examination scores were significantly predicted in the group using ACs (t (169), -2.52, p = .020) but not with the groups using BZD (t (162), 0.84, p = .440). Evidence showed that older adults with Alzheimer’s disease and exposed to ACs exhibited lower global cognitive scores than those without AC exposure. Using ACs could be a trade-off between controlling BPSD and aggravating cognitive impairment. Highlighting the awareness of the potential anticholinergic effect is important and may be the best policy.

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A Bayesian hierarchical change point model with parameter constraints

Statistical Methods in Medical Research ◽

10.1177/0962280220948097 ◽

2020 ◽

pp. 096228022094809

Author(s):

Hong Li ◽

Andreana Benitez ◽

Brian Neelon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Change Point ◽

Normal Aging ◽

Point Model ◽

Bayesian Hierarchical ◽

Random Slope ◽

Change Point Model ◽

Parameter Constraints

Alzheimer’s disease is the leading cause of dementia among adults aged 65 or above. Alzheimer’s disease is characterized by a change point signaling a sudden and prolonged acceleration in cognitive decline. The timing of this change point is of clinical interest because it can be used to establish optimal treatment regimens and schedules. Here, we present a Bayesian hierarchical change point model with a parameter constraint to characterize the rate and timing of cognitive decline among Alzheimer’s disease patients. We allow each patient to have a unique random intercept, random slope before the change point, random change point time, and random slope after the change point. The difference in slope before and after a change point is constrained to be nonpositive, and its parameter space is partitioned into a null region (representing normal aging) and a rejection region (representing accelerated decline). Using the change point time, the estimated slope difference, and the threshold of the null region, we are able to (1) distinguish normal aging patients from those with accelerated cognitive decline, (2) characterize the rate and timing for patients experiencing cognitive decline, and (3) predict personalized risk of progression to dementia due to Alzheimer’s disease. We apply the approach to data from the Religious Orders Study, a national cohort study of aging Catholic nuns, priests, and lay brothers.

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Early detection of Alzheimer’s disease with a total score of the German CERAD

Journal of the International Neuropsychological Society ◽

10.1017/s1355617710000822 ◽

2010 ◽

Vol 16 (5) ◽

pp. 910-920 ◽

Cited By ~ 46

Author(s):

MICHAEL M. EHRENSPERGER ◽

MANFRED BERRES ◽

KIRSTEN I. TAYLOR ◽

ANDREAS U. MONSCH

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Logistic Regression ◽

Correct Classification ◽

Operating Characteristics ◽

Healthy Control ◽

Neuropsychological Assessment Battery ◽

State Examination

AbstractThe goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer’s Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer’s disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.’s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.’s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910–920.)

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