Subclinical Thyroid Dysfunction and Cognitive Decline in Old Age

Background

Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

Methods

Prospective longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests.

Results

Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up.

Conclusion

We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.     

Body Mass Index and Decline of Cognitive Function

Background

The association between body mass index (BMI) and cognitive function is a public health issue. This study investigated the relationship between obesity and cognitive impairment which was assessed by the Korean version of the Mini-mental state examination (K-MMSE) among mid- and old-aged people in South Korea.

Methods

A cohort of 5,125 adults, age 45 or older with normal cognitive function (K-MMSE≥24) at baseline (2006), was derived from the Korean Longitudinal Study of Aging (KLoSA) 2006~2012. The association between baseline BMI and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed baseline BMI and change of cognitive function over the 6-year follow-up using multiple linear regressions.

Results

During the follow-up, 358 cases of severe cognitive impairment were identified. Those with baseline BMI≥25 kg/m² than normal-weight (18.5≤BMI<23 kg/m²) were marginally less likely to experience the development of severe cognitive impairment (adjusted odds ratio [aOR] = 0.73, 95% CI = 0.52 to 1.03; P_trend = 0.03). This relationship was stronger among female (aOR = 0.63, 95% CI = 0.40 to 1.00; P_trend = 0.01) and participants with low-normal K-MMSE score (MMSE: 24–26) at baseline (aOR = 0.59, 95% CI = 0.35 to 0.98; P_trend<0.01). In addition, a slower decline of cognitive function was observed in obese individuals than those with normal weight, especially among women and those with low-normal K-MMSE score at baseline.

Conclusion

In this nationally representative study, we found that obesity was associated with lower risk of cognitive decline among mid- and old-age population.     

Prevalence and Incidence of Memory Complaints in Employed Compared to Non-Employed Aged 55–64 Years and the Role of Employment Characteristics

Objectives

To examine the association of employment status and characteristics with prevalent and incident memory complaints (MC) in 55–64-year-olds.

Methods

Subjects were participants of the Longitudinal Aging Study Amsterdam (LASA). Respondents with baseline data were selected to examine the association of employment status (n = 1525) and employment characteristics (n = 1071) with prevalent MC (i.e., MC at baseline). Respondents without MC at baseline were selected to examine the association of employment (n = 526) and employment characteristics (n = 379; working hours, job prestige, job level, psychological job demands, iso-strain) with incident MC (i.e., no MC at baseline and MC at three-year follow-up). Associations were adjusted for relevant covariates (demographics, memory performance, physical health, mental health, personality traits). Logistic regression was applied. Data were weighed according to gender and age of the Dutch population.

Results

At baseline 20.5% reported MC. At three-year follow-up, 15.4% had incident MC. No associations were found between employment status and MC. Adjusted analysis revealed that individuals with high occupational cognitive demands were more likely to have prevalent MC.

Conclusions

Middle-aged workers are equally as likely to experience MC as non-working age-peers. Among workers, those with cognitively demanding work were more likely to experience MC, independent of memory performance. Memory decline due to ageing may be noticed sooner in 55–64-year-olds performing cognitively demanding work.     

The Implications of Body Fat Mass and Fat Distribution for Cognitive Function in Elderly Women

Objective: To investigate how body fat mass, an established source of endogenous estrogen after menopause, influences cognitive impairment in elderly women. Research Methods and Procedures: Study participants were 5607 generally healthy postmenopausal women with mean age of 63.8 years at baseline followed for an average of 7.3 years. Cognitive function assessed at follow‐up using the short Blessed test was related to baseline body weight, the yearly change in weight, and follow‐up measures of body fat depots assessed by DXA. Cognitive function was also related to various surrogates of lifetime estrogen exposure. Results: Women with the worst cognitive performance (score ≥ 9) at follow‐up were the ones who lost the most body weight and revealed the lowest central fat mass (CFM). The association of weight loss with worse cognitive performance was apparent across all age groups except for those more than 80 years old. In the multivariate logistic model, the risk of cognitive impairment was 18% lower in women in the second quartile of CFM (p = 0.14), 32% lower in the third (p = 0.01), and 48% lower in the fourth (p < 0.001) compared with those in the first quartile. CFM showed significant correlation with the simultaneously measured serum estradiol (r = 0.25; p < 0.001). Cognitive score showed an inverse linear relationship with the duration of reproductive period and bone mineral density assessed at follow‐up. Discussion: These findings argue for a protective association of body fat mass with cognitive impairment in elderly women. This association seems to involve a more prominent exposure to endogenous estrogens.     

Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders

BackgroundAlzheimer’s disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis.ResultsThe overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58–0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people.ConclusionOur study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer’s disease remains elusive.     

Consumption of Green Tea,but Not Black Tea or Coffee,Is Associated with Reduced Risk of Cognitive Decline

Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007–2008), 490 completed the follow up survey in 2011–2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9±0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16–0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25–0.86) among those who consumed green tea 1–6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06–1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors.     

Increased Plasma Levels of Heat Shock Protein 70 Associated with Subsequent Clinical Conversion to Mild Cognitive Impairment in Cognitively Healthy Elderly

Background and Aims

Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline.

Methods

Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed.

Results

After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001).

Conclusions

These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly.     

Insulin is differentially related to cognitive decline and atrophy in Alzheimer's disease and aging

We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer's disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=-0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

OBJECTIVE: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. DESIGN: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. SETTING: Community settings in Oxfordshire. SUBJECTS: 71 subjects with dementia, initially living at home with informant. MAIN OUTCOME MEASURES: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). RESULTS: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P = 0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. CONCLUSIONS: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.     

Amyloid-Related Memory Decline in Preclinical Alzheimer’s Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer’s disease.     

Association of AKAP6 and MIR2113 with cognitive performance in a population‐based sample of older adults

Genetic factors make a substantial contribution to inter‐individual variability in cognitive function. A recent meta‐analysis of genome‐wide association studies identified two loci, AKAP6 and MIR2113, that are associated with general cognitive function. Here, we extend this previous research by investigating the association of MIR2113 and AKAP6 with baseline and longitudinal non‐linear change across a broad spectrum of cognitive domains in a community‐based cohort of older adults without dementia. Two single nucleotide polymorphisms (SNPs), MIR211‐rs10457441 and AKAP6‐rs17522122 were genotyped in 1570 non‐demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association between AKAP6 and MIR2113 with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change. AKAP6‐rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain. MIR2113‐rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes were observed for this SNP. These results confirm the previous finding that AKAP6 is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, while MIR2113 primarily affects the rate at which memory declines over time.     

Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging

BACKGROUND: Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers (CCBs) in older people. This study was undertaken to examine prospectively the association between the use of these and other antihypertensive drugs and cognitive function. METHODS: The authors examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older. The risk of cognitive decline, as indicated by a decline in performance on the Modified Mini-Mental State (3MS) examination over the 5-year period, was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline. RESULTS: The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents (75% v. 59%). The adjusted odds ratio (OR) for a significant decline in cognitive performance (defined as a decrease in 3MS score of 10 points or more) was 2.28 (95% confidence interval [CI] 1.12-4.66) for subjects using CCBs. The adjusted ORs (and 95% CIs) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows: angiotensin-converting-enzyme inhibitor, OR 1.36 (95% CI 0.41-4.55); diuretic or other antihypertensive drug, OR 1.45 (95% CI 0.51-4.14); dihydropyridine CCB (nifedipine), OR 1.94 (95% CI 0.52-7.27) and non-dihydropyridine CCB (diltiazem or verapamil), OR 3.72 (95% CI 1.22-11.36). INTERPRETATION: Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline. These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use, blood pressure and cognitive impairment in elderly patients.     

Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

Objectives

Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline.

Methods

121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points.

Results

Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up.

Conclusions

The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease.     

Visual Impairment,Hearing Loss and Cognitive Function in an Older Population: Longitudinal Findings from the Blue Mountains Eye Study

The presence of visual impairment (VI) and hearing loss (HL) with may be a marker for subsequent cognitive decline over time in older people. A prospective, longitudinal population-based study of the 3654 participants of the Blue Mountains Eye Study were assessed for the associations between VI and HL and a decline in mini-mental state examination (MMSE) scores over a duration of 10 years from the 5-year (baseline of this report) to the 15-year follow-up visits. MMSE was assessed at the 5-, 10- and 15-year follow-up visits. A decline ≥3 scores from 5-year to 10- or 15-year visits indicated possible cognitive decline. VI was defined as best-corrected visual acuity <6/12 in the worse-eye, HL was defined as pure-tone average >40 decibels in the worse-ear and dual sensory impairment (DSI) was defined by the co-presence of VI and HL, detected at 5-year follow-up (baseline of this report). Participants with no VI and HL over the same 5- or 10-year corresponding period were controls. Associations of VI, HL and DSI with possible cognitive decline were assessed using logistic regression models adjusting for age and sex after excluding subjects with a stroke history. The presence of VI, HL or DSI was not associated with possible cognitive decline over 5 years (odds ratio (OR) 0.84, 95% confidence-intervals (CI) 0.40–1.79, OR 1.02, 95% CI 0.61–1.70 and 1.41, 95% CI 0.54–3.72, respectively) or 10 years (OR 1.09, 95% CI 0.52–2.30, OR 1.09, 95% CI 0.65–1.82 and 1.15, 95% CI 0.28–4.73, respectively). There were no changes to these findings after adjustment for other potential confounders. Age was significantly associated with possible cognitive decline (OR 1.07, 95% CI 1.04–1.10 for both periods). Neither visual impairment, hearing loss nor dual sensory impairment was independently associated with subsequent decline in cognition.     

Tea Consumption and Cognitive Impairment: A Cross-Sectional Study among Chinese Elderly

Background

Laboratorial and epidemiological researches suggested that tea exhibited potential neuroprotective effect which may prevent cognitive impairment, but there were few data among the elderly aged 60 years and above in China.

Objective

The objective was to explore the relationship between characteristics of tea consumption and cognitive impairment.

Design

We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program (ZPHS) which was conducted in 2014. Totally 9,375 residents aged 60 years and above were recruited in this study. Face-to-face interview based on a self-developed questionnaire was performed for each participant. Detailed tea consumption habits were included in the questionnaire. Cognitive impairment screening was performed by using Mini-Mental State Examination (MMSE). Education-specific cut-off points for Chinese were applied to determine the status of cognitive impairment. Logistic regression analysis was used to calculate odds ratios (ORs) of cognitive impairment associated with tea consumption.

Results

The means (SD) of MMSE scores for the subjects who did not consume tea and consumed <2 cups/d, 2–4 cups/d, ≥4 cups/d were 23.3 (SD = 5.61), 23.8 (SD = 5.60), 24.5 (SD = 5.63) and 25.0 (SD = 5.08), respectively. An inverse correlation was found between tea consumption (of all types) and prevalence of cognitive impairment. Volume of tea consumption was significantly associated with cognitive impairment: compared with non-consumption participants, those who consumed < 2 cups/d, 2–4 cups/d, and ≥4 cups/d were observed ORs of 0.77 (95% CI: 0.56, 1.07), 0.62 (95% CI: 0.47, 0.81), and 0.49 (95% CI: 0.36, 0.66), respectively. Compared with non-consumption, black tea presented a positive correlation with cognitive function after controlling for potential confounders (OR = 0.52, 95% CI: 0.28, 0.95), while green tea showed no significant difference (OR = 1.04, 95% CI: 0.72, 1.51). Participants who consumed weak tea, moderate tea or strong tea more often were observed a better cognitive status when compared with those who did not have tea, with an OR of 0.51 (95% CI: 0.28, 0.92), 0.32 (95% CI: 0.19, 0.56) and 0.42 (95% CI: 0.22, 0.78) after adjusting for the potential confounders. But there was no statistically significant difference between any two of these ORs.

Conclusion

Black tea consumption was association with better cognitive performance among the elderly aged 60 years and above in China, while green tea presented no correlation. The positive association of cognitive status with tea consumption was not limited to particular type of concentration.     

Dose-Related Effects of Alcohol on Cognitive Functioning

We assessed the suitability of six applied tests of cognitive functioning to provide a single marker for dose-related alcohol intoxication. Numerous studies have demonstrated that alcohol has a deleterious effect on specific areas of cognitive processing but few have compared the effects of alcohol across a wide range of different cognitive processes. Adult participants (N = 56, 32 males, 24 females aged 18–45 years) were randomized to control or alcohol treatments within a mixed design experiment involving multiple-dosages at approximately one hour intervals (attained mean blood alcohol concentrations (BACs) of 0.00, 0.048, 0.082 and 0.10%), employing a battery of six psychometric tests; the Useful Field of View test (UFOV; processing speed together with directed attention); the Self-Ordered Pointing Task (SOPT; working memory); Inspection Time (IT; speed of processing independent from motor responding); the Traveling Salesperson Problem (TSP; strategic optimization); the Sustained Attention to Response Task (SART; vigilance, response inhibition and psychomotor function); and the Trail-Making Test (TMT; cognitive flexibility and psychomotor function). Results demonstrated that impairment is not uniform across different domains of cognitive processing and that both the size of the alcohol effect and the magnitude of effect change across different dose levels are quantitatively different for different cognitive processes. Only IT met the criteria for a marker for wide-spread application: reliable dose-related decline in a basic process as a function of rising BAC level and easy to use non-invasive task properties.     

Neural Substrates of Cognitive Subtypes in Parkinson's Disease: A 3-Year Longitudinal Study

Background

The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinson''s disease (PD) remain to be elucidated.

Methods

Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography.

Results

Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease.

Conclusions

These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.     

Apolipoprotein E4 and memory decline in the elderly

The objective of this study was to investigate whether the association between Apolipoprotein E4 (ApoE4) and memory decline is modified by baseline general cognitive impairment and age in a population-based elderly sample. Subjects were participants in the Longitudinal Aging Study Amsterdam (LASA). The study sample consisted of 1,243 subjects, 62-85 years old, with a Mini-Mental State Examination (MMSE) score between 21-30 and known ApoE phenotypes. Memory performance was measured with a short version of the Auditory Verbal Learning Test (AVLT) at baseline and repeated after three years (N = 854). Memory decline was defined as a decrease of at least one standard deviation from the mean change score on immediate recall, delayed recall and retention. ApoE4 was associated with memory decline in cognitively impaired subjects (MMSE 21-26), but not in cognitively normal subjects (MMSE 27-30). In particular cognitively impaired E4 carriers older than 75 years were at high risk of memory decline. Contrary to AD studies, our study suggests that the risk of ApoE4 on memory decline does not decrease with ageing.     

Population Aging at Cross-Roads: Diverging Secular Trends in Average Cognitive Functioning and Physical Health in the Older Population of Germany

This paper uses individual-level data from the German Socio-Economic Panel to model trends in population health in terms of cognition, physical fitness, and mental health between 2006 and 2012. The focus is on the population aged 50–90. We use a repeated population-based cross-sectional design. As outcome measures, we use SF-12 measures of physical and mental health and the Symbol-Digit Test (SDT) that captures cognitive processing speed. In line with previous research we find a highly significant Flynn effect on cognition; i.e., SDT scores are higher among those who were tested more recently (at the same age). This result holds for men and women, all age groups, and across all levels of education. While we observe a secular improvement in terms of cognitive functioning, at the same time, average physical and mental health has declined. The decline in average physical health is shown to be stronger for men than for women and found to be strongest for low-educated, young-old men aged 50–64: the decline over the 6-year interval in average physical health is estimated to amount to about 0.37 SD, whereas average fluid cognition improved by about 0.29 SD. This pattern of results at the population-level (trends in average population health) stands in interesting contrast to the positive association of physical health and cognitive functioning at the individual-level. The findings underscore the multi-dimensionality of health and the aging process.     

Plasma prion protein concentration and progression of Alzheimer disease

Background/Objective: Recently, PrP^c has been linked to AD pathogenesis. Second, a relation of PrP^c plasma levels with cognitive status and decline of healthy elderly subjects has been reported. Therefore, we hypothesized baseline plasma levels of PrP^c to be associated with AD progression in cognitive and functional domains.Materials and Methods: AD patients (n = 84) were included into an observational study at time of diagnosis. Baseline plasma PrP^c levels were determined. Decline was assessed annually (mean follow-up time 3 years) with the aid of different standardized tests (MMSE, iADL, bADL, GDS, UPDRSIII). Multiple regression analyses were used to uncover potential associations between decline and PrP^c levels.Results: No association of PrP^c and decline could be established. Presence of diabetes mellitus was linked to slower deterioration. Intake of neuroleptic drugs or memantine was associated with faster progression.Conclusion: Plasma PrP^c at baseline could not be shown to be related to AD progression in this study. An interesting association of diabetes mellitus and decline warrants further investigation.