Tasks associated with losing a loved one

This Wall Street Journal article from a couple of weeks ago is addressed to adult children but lots of the information applies to spouses and siblings as well.  The many tasks that come with losing a parent are detailed — sifting through belongings, taking care of financial matters, doling out heirlooms, and documenting tax deductions if items are donated to charities.

Here’s a link to the full article:

online.wsj.com/article/SB10001424052970203920204577195292564700600.html

WEEKEND INVESTOR
Wall Street Journal
The Pearls Are Mine!
By Kelly Greene
February 4, 2012

Robin

 

UCLA uses PET scans to study tau tangles

This news out of UCLA on Monday February 13th has relevance for the PSP (progressive supranuclear palsy) and CBD (corticobasal degeneration) communities.  Both PSP and CBD are disorders of tau.  In Alzheimer’s Disease (AD), tau is a problem along with a second protein called beta amyloid.  A couple of years ago, researchers out of the University of Pittsburgh developed a compound that attaches itself to amyloid in the brain such that PET scans can help identify those with a high chance of having Alzheimer’s Disease.  A year or so ago, it was announced that researchers at UCLA had developed a compound that attaches itself to tau in the brain such that PET scans can help identify those with tauopathies, such as AD, PSP, and CBD.

This study published out of UCLA this week is about using this new PET scan compound to identify which subjects had tau tangles in the brain and predicted which subjects would experience cognitive decline.  Though this particular study focused on mild cognitive impairment (which can “convert” to Alzheimer’s Disease), it has implications for the PSP and CBD communities.

The full press release is copied below.  (Note that there are quite a few typos in this press release.)

Robin

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newsroom.ucla.edu/portal/ucla/ucla-imaging-technique-predicts-220856.aspx

UCLA brain-imaging technique predicts who will suffer cognitive decline over time
By Rachel Champeau
UCLA Newsroom
February 13, 2012

Cognitive loss and brain degeneration currently affect millions of adults, and the number will increase, given the population of aging baby boomers. Today, nearly 20 percent of people age 65 or older suffer from mild cognitive impairment and 10 percent have dementia.

UCLA scientists previously developed a brain-imaging tool to help assess the neurological changes associated with these conditions. The UCLA team now reports in the February issue of the journal Archives of Neurology that the brain-scan technique effectively tracked and predicted cognitive decline over a two-year period.

The team has created a chemical marker called FDDNP that binds to both plaque and tangle deposits — the hallmarks of Alzheimer’s disease — which can then be viewed using a positron emission tomography (PET) brain scan, providing a “window into the brain.” Using this method, researchers are able to pinpoint where in the brain these abnormal protein deposits are accumulating.

“We are finding that this may be a useful neuro-imaging marker that can detect changes early, before symptoms appear, and it may be helpful in tracking changes in the brain over time,” said study author Dr. Gary Small, UCLA’s Parlow–Solomon Professor on Aging and a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Small noted that FDDNP–PET scanning is the only available brain-imaging technique that can assess tau tangles. Autopsy findings have found that tangles correlate with Alzheimer’s disease progression much better than do plaques.

For the study, researchers performed brain scans and cognitive assessments on the subjects at baseline and then again two years later. The study involved 43 volunteer paricipants, with an average age of 64, who did not have dementia. At the start of the study, approximately half (22) of the participants had normal aging and the other half (21) had mild cognitive impairment, or MCI, a condition that increases a person’s risk of developing Alzheimer’s disease.

Researchers found that for both groups, increases in FDDNP binding in the frontal, posterior cingulate and global areas of the brain at the two-year follow-up correlated with progression of cognitive decline. These areas of the brain are involved in decision-making, complex reasoning, memory and emotions. Higher initial baseline FDDNP binding in both subject groups was associated with a decline in cognitive functioning in areas such as language and attention at the two-year follow-up.

“We found that increases in FDDNP binding in key brain areas correlated with increases in clinical symptoms over time,” said study author Dr. Jorge R. Barrio, who holds UCLA’s Plott Chair in Gerentology and is a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA. “Initial binding levels were also predictive of future cognitive decline.”

Among the subjects with mild cognitive impairment, the level of initial binding in the frontal and parietal areas of the brain provided the greatest accuracy in identifying those who developed Alzheimer’s disease after two years. Of the 21 subjects with MCI, six were diagnosed with Alzheimer’s at follow-up, and these six subjects had higher initial frontal and parietal binding values than the other subjects in the MCI group.

In the normal aging subjects, three developed mild cognitive impairment after two years. Two of these three participants had had the highest baseline binding values in the temporal, parietal and frontal brain regions among this group.

Researchers said the next step in research will involve a longer duration of follow-up with larger samples of subjects. In addition, the team is using this brain-imaging technique in clinical trials to help track novel therapeutics for brain aging, such as curcumin, a chemical found in turmeric spice.

“Tracking the effectiveness of such treatments may help accelerate drug discovery efforts,” Small, the author of the new book “The Alzheimer’s Prevention Program,” said. “Because FDDNP appears to predict who will develop dementia, it may be particularly useful in tracking the effectiveness of interventions designed to delay the onset of dementia symptoms and eventually prevent the disease.”

Small recently received research approval from the U.S. Food and Drug Administration to use FDDNP–PET to study people with mild cognitive impairment to determine whether a high-potency form of curcumin — a spice with anti-amyloid, anti-tau and anti-inflammatory properties — can prevent Alzheimer’s disease and the accumulation of plaques and tangles in the brain.

UCLA owns three U.S. patents on the FDDNP chemical marker. The Office of Intellectual Property at UCLA is actively seeking a commercial partner to bring this promising technology to market.

Small and study authors Jorge R. Barrio and S. C. Huang are among the inventors. Disclosures are listed in the full study.

Additional authors included Prabha Siddarth, Linda M. Ercoli, Alison C. Burggren, Karen J. Miller, Dr. Helen Lavretsky and Dr. Susan Y. Bookheimer, all of the UCLA Department of Psychiatry and Biobehavioral Sciences, and Vladimir Kepe and S.C. Huang, who are part of the UCLA Department of Molecular and Medical Pharmacology.

The study was funded by the National Institutes of Health and the U.S. Department of Energy.

Cognitive decline similar in LBD and AD

This is an interesting study of 58 DLB (Dementia with Lewy Bodies) subjects and 100 AD (Alzheimer’s Disease) subjects, followed over a one-year period at 40 European centers. All patients had mild-moderate dementia. The diagnosis required a 123I-FP-CIT (dopamine transporter) SPECT. (There was no autopsy confirmation of the diagnoses.)

The authors state that DLB is associated with “earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer’s disease.”

The authors believe prognosis info is important information for caregivers:

“Awareness of the rate of cognitive decline and also of non-cognitive symptoms can help carers and patients to adjust and plan appropriate lifestyle changes and to make arrangements for the future. This frequently involves making difficult decisions regarding treatment of psychiatric and motor symptoms and utilisation of limited resources available for patients with dementia.”

The authors want to investigate why the prognosis in DLB is worse than in AD. They thought perhaps it was due to a faster cognitive decline in DLB as compared to AD. In fact, they found that there were no significant differences when comparing the rates of decline of cognitive and neuropsychiatric symptoms in DLB and AD. One of the key messages of the article is: “the worse prognosis of DLB is likely to be mediated by neuropsychiatric or other symptoms and not only by cognitive decline.”

I’ve copied the abstract below.

Robin

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BMJ Open. 2012 Feb 8.

Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer’s disease: a cohort study.

Walker Z, McKeith I, Rodda J, Qassem T, Tatsch K, Booij J, Darcourt J, O’Brien J.
Research Department of Mental Health Sciences, University College London, Bloomsbury Campus, London, UK.

Abstract

OBJECTIVES:
Dementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer’s disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future.

DESIGN:
In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures.

SETTING:
Patients were recruited from 40 European centres.

PARTICIPANTS:
Subjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging.

OUTCOME MEASURES:
The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI).

RESULTS:
The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed.

CONCLUSIONS:
DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.

PubMed ID#: 22318660 (www.pubmed.gov/ID#22318660)

Treatment Options for PSP, CBD, and FTD (Review)

This medical journal article is a review of what we know about treatment of PSP (progressive supranuclear palsy), CBD (corticobasal degeneration), and FTD (frontotemporal dementia). Some general statements are made about “diet and lifestyle,” then several medications are discussed including anti-depressants (SSRIs in particular), dementia medications, antipsychotics, and levodopa. Finally, “emerging therapies” are briefly described.

I’ve copied the abstract below.

For me, the one new piece of information is that Abilify and Seroquel are the two most commonly prescribed antipsychotics “in parkinsonian disorders.” It would be interesting to know how frequently they are prescribed in PSP and CBD. Certainly most of the prescriptions are for Parkinson’s Disease and Parkinson’s Disease Dementia (Lewy Body Dementia). Though we have a few local support group members with PSP and CBD taking these medications, the majority do not.

Robin

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Current Treatment Options in Neurology. 2012 Feb 4. [Epub ahead of print]

Treatment Options for Tauopathies.

Karakaya T, Fußer F, Prvulovic D, Hampel H.
Department of Psychiatry, J.W. Goethe-University, Frankfurt, Germany.

Abstract
OPINION STATEMENT: To date, there are no approved and established pharmacologic treatment options for tauopathies, a very heterogenous group of neuropsychiatric diseases often leading to dementia and clinically diagnosed as atypical Parkinson syndromes.

Among these so-called Parkinson plus syndromes are progressive supranuclear palsy (PSP), also referred to as Steele-Richardson-Olszewski syndrome; frontotemporal dementia (FTD); and corticobasal degeneration (CBD).

Available treatment strategies are based mainly on small clinical trials, miscellaneous case reports, or small case-controlled studies. The results of these studies and conclusions about the efficacy of the medication used are often contradictory.

Approved therapeutic agents for Alzheimer´s dementia, such as acetylcholinesterase inhibitors and memantine, have been used off-label to treat cognitive and behavioral symptoms in tauopathies, but the outcome has not been consistent.

Therapeutic agents for the symptomatic treatment of Parkinson’s disease (levodopa or dopamine agonists) are used for motor symptoms in tauopathies.

For behavioral or psychopathological symptoms, treatment with antidepressants-especially selective serotonin reuptake inhibitors-could be helpful.

Antipsychotics are often not well tolerated because of their adverse effects, which are pronounced in tauopathies; these drugs should be given very carefully because of an increased risk of cerebrovascular events.

In addition to pharmacologic options, physical, occupational, or speech therapy can be applied to improve functional abilities.

Each pharmacologic or nonpharmacologic intervention should be fitted to the specific symptoms of the individual patient, and decisions about the type and duration of treatment should be based on its efficacy for the individual and the patient’s tolerance.

Currently, no effective treatment is available that targets the cause of these diseases. Current research focuses on targeting tau protein pathology, including pathologic aggregation or phosphorylation; these approaches seem to be very promising.

PubMed ID: #22307450 (see pubmed.gov for this abstract only)

Dopamine Transporter Loss Differs in MSA, PSP and PD

With a special PET scan that focuses on dopamine transport, these Korean researchers concluded that PSP (progressive supranuclear palsy) patients showed “more prominent and earlier dopamine transporter loss” in the anterior caudate, a region of the brain, and that MSA (multiple system atrophy) patients showed “more prominent and earlier dopamine transporter loss” in the ventral putamen, another region of the brain, when compared to Parkinson’s Disease.

None of the diagnoses are autopsy-confirmed, which is what is needed for the medical community to embrace this sort of PET scan.

I’ve copied the abstract below.

Robin

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Journal of Nuclear Medicine. 2012 Feb 9. [Epub ahead of print]

Subregional Patterns of Preferential Striatal Dopamine Transporter Loss Differ in Parkinson Disease, Progressive Supranuclear Palsy, and Multiple-System Atrophy.

Oh M, Kim JS, Kim JY, Shin KH, Park SH, Kim HO, Moon DH, Oh SJ, Chung SJ, Lee CS.
Department of Nuclear Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.

Abstract
Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of (18)F-fluorinated-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET in differentiating PSP and MSA from PD.

METHODS:
Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with (18)F-FP-CIT PET.

The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum [VS], anterior caudate [AC], posterior caudate, anterior putamen, posterior putamen [PP], and ventral putamen [VP]) and 1 occipital VOI template. The nondisplaceable binding potential (BP(ND)) and intersubregional ratio (ISR; defined as the ratio of the BP(ND) of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated.

RESULTS:
The BP(ND) of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P < 0.05). The BP(ND) of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BP(ND) of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (<0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (>0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively.

The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD.

CONCLUSION:
Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features.

PubMed ID#: 22323779 (see pubmed.gov for this abstract only)