Focus on memory disorders - PowerPoint Presentation

Slide1

Focus on memory disordersDebra m. barnett, md, dfapaArea Agency on Aging of Pasco-pinellasApril 22, 2016

IMPROVING MENTAL HEALTH IN SENIORSSlide2

Known Risk Factors- DementiasAgeOf those with Alzheimer’s, <65yo- 4%65yo to 74yo- 6%75yo to 84yo- 44%>85yo- 46%Basically doubles every five years after 65yoAll dementias- 13.9% of people over 71yo

(based on estimates from Aging, Demographics, and Memory Study (ADAMS) Slide3

Known Risk Factors- DementiasFamily History- combination of genetics and envirnmentGeneticsAPO E4Not determinativeOne copy- maybe 3 x riskTwo copies- 20x riskEarly onset forms and specific genes

Three proteins:

Amyloid

precursor protein

Presenilin-1

Presenilin-2

Autosomal

dominant- determinative

Rare- a few hundred families, <5% of the casesSlide4

Known Risk Factors- DementiasGender?Higher incidence for womenSome studies find increased risk for women, but differences in educational attainment may effect the results If true, why?- Loss of the protective effect of estrogen; but studies have not shown HRT helps prevent dementiaSlide5

Strength of the evidenceModifiable FactorsSlide6

Modifiable FactorsExercise (LTPA= Leisure time physical activity)Theoretically can help by improving health (cardiovascular effects)No or low LTPA= worse executive fcn, semantic memory, and processing speed; insignificant after adjusting for vascular risk factors. Cognitively unimpaired ind.s with no/low LTPA vs mod/high declined more over time in processing speed. “equal to 10 more years of aging” (Neurology, Wiley et. al., 03/23/2016)Slide7

Modifiable FactorsSleep patternsEffects of chronic insomniaIn healthy older adults, chronic insomnia produced differences in memory span, sustained attention, and executive functioning.Excessive daytime sleepiness has been associated with (determinative) cardio-cerebrovascular disease and AD.Insomnia during a period of long follow-up was associated with incident cases of AD.

Effects of Sleep Apnea

Younger age of onset of MCI or AD

Use of CPAP seems to modify the riskSlide8

Modifiable FactorsDepression?Prodrome, risk factor (causation), or consequence?Neurodegenerative processes of Alzheimer’s begin 6-8 years before it is clinically apparent.Late onset depression is itself associated with neuronal changes .Individuals may be self aware of increasing (though still sub-clinical) cognitive difficulties.“Subjects with early onset depression had an increased risk for AD (HR 3.76; 95% CI 1.41 to 10.06), independent of

hippocampal

and

amygdalar

volume, whereas this risk was 2.34 (95% CI 0.82 to 6.69) in subjects with a late-onset depression.” (Neurology,

Geerlings

et. al., 04/08/2008)

“the underlying

neuropathological

condition that causes MCI or dementia also causes depressive symptoms”, placing late-life depression, MCI, and dementia on a possible clinical continuum. (AJGP,

Panza

et. al., Feb 2010)Slide9

Modifiable FactorsAnxiety- consistently confirmedA past anxiety diagnosis was associated with a future dementia diagnosis [odds ratio 2.76 (95% confidence interval 2.11–3.62). Depression contributed less to the risk. (Fam Pract, C. Burton et. al., Feb 2013)“There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not.” (Alzheimer’s and Dementia, Andrew J.

Petkus

et. al., April 2016)

Do medications change the risk? Benzodiazepines- probably not. Not known for other meds.

No such thing as a stress-free life, but individuals can work on their own patterns of response to stressors. Consider psychotherapy, meditation, guided imagery and visualization, hypnosis, deep breathing, massage, spiritual support

From a public health standpoint, efforts to reduce poverty, unemployment, hunger, violence, may reduce population risk for dementia.Slide10

Modifiable FactorsMedications- BenzodiazepinesIs the risk an effect of the med or related to anxiety?A stronger association was found for longer term exposure and higher exposure “density”, suggesting the relationship for medication and dementia, not just anxiety state. (BMJ, Sophie Billioti de Gage et. al., Sep 2014)No relationship found. (BMJ, Shelly Gray et. al., Feb 2016)In the presence of subtle cognitive changes, the “vulnerable brain”, these meds can have more profound

amnestic

effects.Slide11

Modifiable FactorsMedications- AnticholinergicsAs with Benzodiazepines, the “vulnerable brain will respond more profoundly. These individuals could be found to have MCI- 80% in one study.Do not progress to AD (BMJ, Ancelin et. al., Feb 2006; J Alzheimer’s Dis., Whalley

et. al., 2012).

Another group followed for 10 years showed steeper annual decline in cognitive functioning (

PLoS

ONE, Raj Shah et. al., May 2013).

In addition to greater

cogntive

impairment, there was an increased rate of mortality (J Am

Geriatr

Soc, C. Fox et. al., Aug 2011).Slide12

Modifiable FactorsAntidepressantsPossibly not helpful to treat depression with dementia, and risk for adverse events is higher.Some evidence for reduction of agitation and behavioral problems.Research in MDD has shown that ADTs increase BDNF (Brain-derived Neurotrophic Factor). Decreased BDNF is found in both MDD and AD.Research using Citalopram showed decreased beta-

amyloid

production in healthy individuals (37%) and AD mice (78%) (

Sci

Transl

Med, Yvette

Sheline

et. al., May 2014).Slide13

Modifiable FactorsCaffeineFrom “bench research”, Caffeine was shown to suppress beta-amyloid in mice (J Alzheimers Dis, Chuanhai Cao et. al., 2009).

Caffeinated, not decaf, coffee provided to mice decreased beta-

amyloid

at an equivalent human dose of 500mg daily (J

Alzheimers

Dis

, GW

Arendash

et. al., 2010)

Studies in

coffe

drinkers (humans) had been mixed, but this showed 3-5 cups at mid-life reduced risk of dementia by 65% in late life (J

Alzheimers

Dis

, MH

Eskelinen

et. al., 2010)

Green Tea

EGCG inhibits beta-

amyloid

induced cognitive dysfunction in mice, confirmed previous work on reduction of beta-

amyloib

through alpha-

secretase

(Brain Res.,

Rezai-Zadeh

et. al., Jun 2008).Slide14

Modifiable FactorsEstrogensPhytoestrogens given to ovariectomized rats enhanced spatial memory and spine density in the hippocampus and PFC (Brain Research, V. Luine et. al., Sep 2006).Mixed studies in women using HRT, butModest benefit in Japanese women using unopposed estrogen over two years (Arch Intern Med, MM Rice et. al., 2000).

Estrogen alone helped on subsets of executive tests (

Neuropsychol

Dev

Cogn

, DJ

Wegesin

et. al., May 2007).

Timing of ERT may be important. In the pilot study, REMEMBER, early initiation may be helpful but later use may be harmful (Menopause, AH

Maclellan

et. al., Jan 2006).Slide15

Modifiable FactorsUse of supplements?Omega-3 fatty acids-No improvement in AD mice so probably not useful for a high risk individual (Neuroscience, GW Arendash et. al., Oct 2007).Antioxidants/Vitamins- Mixed reports but highly promoted.Antioxidant supplementation did not slow cognitive change among women with preexisting CVD or CVD risk factors (Circulation, JH Kang et. al., Jun 2009).

Ginkgo

biloba

- mixed findings.

Folic acid-

Metabolism alterations found in MDD.

Related to

Homocysteine

levels and cardiovascular disease, stroke.

Mixed evidence for preventing cognitive decline.Slide16

Modifiable FactorsBrain exercises?BBC conducted a study, Brain Test Britain, and found some positive results in the 60+ yo participants.Widely promoted, not just by the commercial interests, but by major organizations and agencies (NIA).UT-Dallas showed changes on testing and fMRI with strategy-based cognitive training in individuals 56yo to 71yo, published in Cerebral Cortex.

An Australian group found modest results.Slide17

Modifiable FactorsOthersSocial participationAvoid brain traumaCardiovascular HealthSlide18

In SummarySome things we can’t change- age, genetics.Cognitive decline, especially AD, is related to vascular health and mental health.Role for anxiety, depression, brain trauma and mid-life stress in the development of dementia.Exercise, sleep, socialization are important. Probably brain training.Maybe helpful- antidepressants, caffeine, green tea.Some medications may be harmful- anticholinergics

, benzodiazepines.