Categories
Dementia Motor neurone disease

Do pre-symptomatic c9orf72 carriers have a brain MRI signature?

Gyrification abnormalities in presymptomatic c9orf72 expansion carriers

Caverzasi E, Battistella G, Chu SA, et al.

JNNP 2019; 90:1005-1010.

Abstract

OBJECTIVE:

To investigate in-vivo cortical gyrification patterns measured by the local gyrification index (lGI) in presymptomatic c9orf72 expansion carriers compared with healthy controls, and investigate relationships between lGI and cortical thickness, an established morphometric measure of neurodegeneration.

METHODS:

We assessed cortical gyrification and thickness patterns in a cohort of 15 presymptomatic c9orf72 expansion carriers (age 43.7 ± 10.2 years, 9 females) compared with 67 (age 42.4 ± 12.4 years, 36 females) age and sex matched healthy controls using the dedicated Freesurfer pipeline.

RESULTS:

Compared with controls, presymptomatic carriers showed significantly lower lGI in left frontal and right parieto-occipital regions. Interestingly, those areas with abnormal gyrification in presymptomatic carriers showed no concomitant cortical thickness abnormality. Overall, for both presymptomatic carriers and healthy controls, gyrification and cortical thickness measures were not correlated, suggesting that gyrification captures a feature distinct from cortical thickness.

CONCLUSIONS:

Presymptomatic c9orf72 expansion carriers show regions of abnormally low gyrification as early as their 30s, decades before expected symptom onset. Cortical gyrification represents a novel grey matter metric distinctive from grey matter thickness or volume and detects differences in presymptomatic carriers at an early age.

This paper is now cited in the neurochecklist:

Motor neurone disease (MND): C9orf72 variant

Abstract link

By U.S. National Library of Medicine – http://ghr.nlm.nih.gov/gene/C9orf72, Public Domain, Link
Categories
Dementia

Do mushrooms protect against cognitive impairment?

The association between mushroom consumption and mild cognitive impairment: a community-based cross-sectional study in Singapore.

Feng L, Cheah IK, Ng MM, et al.

J Alzheimers Dis 2019; 68:197-203.

Abstract

Background:

We examined the cross-sectional association between mushroom intake and mild cognitive impairment (MCI) using data from 663 participants aged 60 and above from the Diet and Healthy Aging (DaHA) study in Singapore.

Results:

Compared with participants who consumed mushrooms less than once per week, participants who consumed mushrooms >2 portions per week had reduced odds of having MCI (odds ratio = 0.43, 95% CI 0.23-0.78, p = 0.006) and this association was independent of age, gender, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities.

Conclusions:

Our cross-sectional data support the potential role of mushrooms and their bioactive compounds in delaying neurodegeneration.

This paper is cited in the neurochecklist:

Mild cognitive impairment (MCI): clinical features

Abstract link

Fresh champignon mushrooms. Marco Verch on Flickr. https://www.flickr.com/photos/30478819@N08/32797873038
Categories
Dementia normal pressure hydrocephalus

Is normal pressure hydrocephalus a risk factor for Alzheimer’s disease?

Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus

Pomeraniec IJ, Taylor DG, Bond AE, Lopes MB

J Neurosurg Sci 2018 (Epub ahead of print)

Abstract

BACKGROUND:

Patients with normal pressure hydrocephalus (NPH) and Alzheimer’s dementia (AD) can often present with similar symptoms. NPH remains a clinical diagnosis and there are reported shared underlying dynamics of cerebrospinal fluid (CSF) flow and histopathology with patients with biopsy-proven AD.

METHODS:

This is a review on the histopathology and cerebrospinal fluid dynamics of both NPH and AD. In a prior study at the University of Virginia, the authors reviewed patients over a 15 year period who were shunted for a preoperative diagnosis of NPH. Of these patients, 74% received high volume lumbar puncture and at the time of surgery, 159 total biopsies were performed on 113 patients with 46 repeat biopsies. The results of high-volume lumbar punctures, cortical brain biopsies, and clinical outcomes were compared between patients with NPH and those found to have Alzheimer’s pathology.

RESULTS:

As many as 24% of patients with clinical diagnosis of NPH may demonstrate concomitant Alzheimer’s dementia based on histopathological biopsy performed at the time of shunt placement. In patients in whom a CSF shunt was placed and biopsy obtained, 19% of patients demonstrated histopathologiy consistent with CERAD diagnosis of AD. However, more than half (53%) of all patients demonstrated some degree of neuritic plaque development, while 14% and 9% demonstrated evidence of neurofibrillary tangles and amyloid angiopathy, respectively. The improved clinical response seen with HVLP was not sustained following shunt insertion; 45% of NPH patients with positive response to HVLP improved following shunt placement compared to just 18% of concurrent NPH and AD patients (p = 0.0136).

CONCLUSIONS:

There is a high prevalence of AD in patients who are shunted for a clinical diagnosis of NPH. The presenting symptoms of NPH and AD may be very similar and the significant difference in histopathology is what separates the two disease processes. There may be temporary relief with restoring cerebrospinal fluid flow but the presence of underlying neurodegenerative changes more directly correlates with long-term outcomes. There may also be a direct correlation between altered CSF dynamics in both the metabolic clearance and the development of dementia.

Also see

Allali G, Laidet M, Armand S, Assal F. Brain comorbidities in normal pressure hydrocephalus. Eur J Neurol 2018; 25:542-548.

Both references are cited in the neurochecklist:

Normal pressure hydrocephalus (NPH): clinical features

Abstract link 1

Abstract link 2

By Nevit Dilmen (talk) – Own work, CC BY-SA 3.0, Link
Categories
Dementia

Could a diabetes medicine protect against dementia?

Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Orkaby AR, Cho K, Cormack J, Gagnon DR, Driver JA.

Neurology 2017; 89:1877-1885.

Abstract

OBJECTIVE:

To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.

METHODS:

This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.

RESULTS:

We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61-0.73) and 0.78 (95% CI 0.72-0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79-0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87-1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63-0.91), had good renal function (HR 0.86; 95% CI 0.76-0.97), and were white (HR 0.87; 95% CI 0.77-0.99).

CONCLUSIONS:

After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

This reference is cited in the neurochecklist:

Alzheimer’s disease (AD): risk factors

Abstract link

Brain Inflammation in Alzheimer’s Disease. NIH Image Gallery in Flickr. https://www.flickr.com/photos/nihgov/38730047881
Categories
Dementia Neuropsychiatry

Is dementia risk reduced by drinking water lithium levels?

Association of lithium in drinking water with the incidence of dementia

Kessing LV, Gerds TA, Knudsen NN, et al.

JAMA Psychiatry 2017; 74:1005-1010.

Abstract

IMPORTANCE:

Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition.

OBJECTIVE:

To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water.

DESIGN, SETTING, AND PARTICIPANTS:

This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population. The mean lithium exposure in drinking water since 1986 was estimated for all study individuals. Data analysis was performed from January 1, 1995, through December 31, 2013.

MAIN OUTCOMES AND MEASURES:

A diagnosis of dementia in a hospital inpatient or outpatient contact. Diagnoses of Alzheimer disease and vascular dementia were secondary outcome measures. In primary analyses, distribution of lithium exposure was compared between patients with dementia and controls.

RESULTS:

A total of 73 731 patients with dementia and 733 653 controls (median age, 80.3 years; interquartile range, 74.9-84.6 years; 44 760 female [60.7%] and 28 971 male [39.3%]) were included in the study. Lithium exposure was statistically significantly different between patients with a diagnosis of dementia (median, 11.5 µg/L; interquartile range, 6.5-14.9 µg/L) and controls (median, 12.2 µg/L; interquartile range, 7.3-16.0 µg/L; P < .001). A nonlinear association was observed. Compared with individuals exposed to 2.0 to 5.0 µg/L, the incidence rate ratio (IRR) of dementia was decreased in those exposed to more than 15.0 µg/L (IRR, 0.83; 95% CI, 0.81-0.85; P < .001) and 10.1 to 15.0 µg/L (IRR, 0.98; 95% CI, 0.96-1.01; P = .17) and increased with 5.1 to 10.0 µg/L (IRR, 1.22; 95% CI, 1.19-1.25; P < .001). Similar patterns were found with Alzheimer disease and vascular dementia as outcomes.

CONCLUSIONS AND RELEVANCE:

Long-term increased lithium exposure in drinking water may be associated with a lower incidence of dementia in a nonlinear way; however, confounding from other factors associated with municipality of residence cannot be excluded.

 

This reference is now cited in the neurochecklist:

Alzheimer’s disease (AD): risk factors

Abstract link

By Dnn87Self-photographed, CC BY 3.0, Link

Categories
Dementia

Is polycystic kidney disease a risk factor for dementia?

Polycystic kidney disease is significantly associated with dementia risk.

Yu TM, Chuang YW, Sun KT, et al.

Neurology 2017; 89:1457-1463.

Abstract

OBJECTIVE:

Data on the risk of neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD), in patients with polycystic kidney disease (PKD) are lacking.

METHODS:

A total of 4,229 patients who were aged ≥20 years and had received a diagnosis of PKD were included in the PKD cohort. For each PKD case identified, 1 participant aged ≥20 years without a history of PKD, dementia, or PD was selected from the comparison cohort. For each patient with PKD, the corresponding controls were selected 1:1 on the basis of the nearest propensity score calculated using logistic regression.

RESULTS:

The incidence density rates of dementia were 4.31 and 2.50 per 1,000 person-years in the PKD and control cohorts, respectively. A 2.04-fold higher risk of dementia was observed in patients with PKD than in controls (adjusted hazard ratio [aHR] 2.04; 95% confidence interval [CI] 1.46-2.85). Regarding the risk of different dementia subtypes, including AD and vascular dementia (VaD), the aHR for AD and presenile dementia was 2.71 (95% CI 1.08-6.75) and that for VaD was 0.90 (95% CI 0.43-1.87) in patients with PKD compared with controls, after adjustment for age, sex, and comorbidities. Compared with controls, the risk of PD increased by 1.78-fold (95% CI 1.14-2.79) in patients with PKD.

CONCLUSIONS:

In clinical practice, health care professionals should be aware of the risk of neurodegenerative diseases in patients with PKD.

This reference is included in the neurochecklist:

Alzheimer’s disease (AD): risk factors

Abstract link

By Ed Uthman from Houston, TX, USA – Adult Polycystic Kidney, CC BY 2.0, Link

 

Categories
Dementia

Do proton pump inhibitors increase the risk of dementia?

Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis

Gomm W, von Holt K, Thomé F, et al

JAMA Neurol 2016; 73:410-416.

Abstract

Importance:

Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective:

To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Methods:

We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.

Results:

A total of 73,679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70,729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

Conclusions:

The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

The following is a related reference:

Haenisch B, von Holt K, Wiese B, et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015; 265:419-428.


Both references are included in the neurochecklist:

Alzheimer’s disease (AD): risk factors

Abstract link 1

Abstract link 2

By Original uploader was Stable attractor at en.wikipedia – Transferred from en.wikipedia to Commons., Public Domain, Link

 

Categories
Dementia Stroke

Do artificial sweeteners increase the risk of stroke and dementia?

Sugar and artificially sweetened beverages and the risks of incident stroke and dementia: a prospective cohort study.

Pase MP, Himali JJ, Beiser AS, et al.

Stroke 2017; 48:1139-1146.

Abstract

Background:

Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort.

Methods:

We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food-frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998), and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10 years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease).

Results:

After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26–6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18–7.07) for Alzheimer’s disease. Sugar-sweetened beverages were not associated with stroke or dementia.

Conclusions:

Artificially sweetened soft drink consumption was associated with a higher risk of stroke and dementia.


This reference is cited in the neurochecklists:

Alzheimer’s disease (AD): risk factors

Ischaemic stroke: non-genetic risk factors

Abstract link

Categories
Dementia

What has Diogenes got to do with frontotemporal dementia?

Diogenes syndrome in frontotemporal dementia

Finney CM, Mendez MF.

Am J Alzheimers Dis Other Demen 2017 (Epub ahead of print)

Abstract

Background:

Diogenes syndrome refers to the combination of extreme self-neglect and excessive collecting with clutter and squalor, which is often present in patients with dementia.

Methods:

Diogenes syndrome may be particularly common in behavioral variant frontotemporal dementia (bvFTD), and the investigation of these patients may help clarify the nature of this syndrome.

Results:

We describe 5 patients with bvFTD who exhibited a decline in self-care accompanied by hoarding behaviors. These patients, and a review of the literature, suggest a combination of frontal lobe disturbances: loss of insight or self-awareness with a failure to clean up or discard, a general compulsive drive, and an innate impulse to take environmental items. This impulse may be part of the environmental dependency syndrome in frontal disease, with specific involvement of a right frontolimbic-striatal system.

Conclusions:

Further investigation of the similarities and mechanisms of these symptoms in bvFTD could help in understanding Diogenes syndrome and lead to potential treatment options.

Frontotemporal dementia (FTD): behavioural variant

 

Abstract link

 

Diogenes the cynic. Now Idonoa on Flikr. https://www.flickr.com/photos/nowidonoa/15146904117