Screening and Treatment of Age-associated cognitive changes that do - - PowerPoint PPT Presentation

Victor W. Henderson, MD, MS Professor, Dept. of Health Research & Policy and of Neurology & Neurological Sciences Director, Stanford Alzheimer’s Disease Research Center

Disclosures: NIH grant support; no conflicts; discussion may include unapproved therapies.

Pre-Meeting Symposium

Screening and Treatment of Cognitive Complaints in Midlife

S t a n f o r d A l z h e i m e r ’ s D i s e a s e R e s e a r c h C e n t e r

f o r h e a l t h y b r a i n a g i n g

V.W. Henderson 05 Oct . 2016 / NAMS Pre-Meeing Symposium 2

Cognitive aging (normal brain aging)

 Age-associated cognitive changes that do not – in themselves –

cause dementia

Abnormal brain aging

 Age-associated cognitive changes that can – in themselves –

cause dementia

 Mild cognitive impairment (MCI) represents an intermediate stage

• f abnormal brain aging

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10 20 30 40 50 60 50 60 70 80 90 100

Cases per 1000- person years Age, years

Incidence rates (women) Rochester, Minnesota

Edland et al., Arch. Neurol. 2002;59:1589

Dementia is rare before age 65

Dementia

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18-29 30-39 40-49 50-59 60-69 70-85 70 80 90 100 110 120 130

Mean composite score Age, years

Men Women

Cognitive aging: affects “fluid” intelligence

Abilities based on new learning, abstract reasoning, and problem solving

Based on Slotkin et al., NIH Toolbox Technical Manual, 2012

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Memory complaints are common during midlife

“During the past week, have you had particular trouble remembering recent events, such as items in the newspaper or

• n TV, or what someone

told you?” 67% reported some degree of memory loss Melbourne Women’s Midlife Health Project 249 women, ages 55-66

Szoeke, Clark, Guthrie, Dennerstein, Henderson

“Have you noticed any changes in your memory over the past few years?” 62% responded YES. Seattle Midlife Women’s Health Study 230 women, mean age 47

Mitchell ES & Woods NF, J. Womens Health Gend. Based Med. 10:351, 2001

No difference in objective episodic memory scores

Weber, Mapstone, Staskiewwicz, Maki, Menopause 7:735, 2013

Rochester, NY 75 women, ages 40-60 Memory Functioning Questionnaire No correlation with learning/ memory scores; correlation with attentional/ working memory scores 36% responded YES.

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Gold EB, Am. J. Epidemiol. 2000;152:463

“Forgetfulness” during past 2 weeks (yes/no)

SWAN

16,065 women, age 40-55 years

10 20 30 40 50 60 70 80 90 100

Percent forgetful Pre- menopausal Early Peri- Late Peri- Post- menopausal Surgical

Associated with age, lower education, not being able to pay for basics, not being employed full-time, past smoking, and less physical activity.

Memory complaints are common during midlife

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Memory complaints are common

after Neugarten & Kraines, Psychosomatic Medicine 1965;27:266.

20 40 60 80 100 13-18 20-29 30-44 45-54 45-54 55-64

Percent forgetful Age

Pre- or post- menopausal Pre- or post- menopausal Menopause transition Menopause transition

460 Chicago area women, no surgical menopause

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“Are you concerned about your memory?”

No memory concern Memory concern

100 80 60 40 20

Percent passing

<75 75-84 >84

Age

25% 75% N = 2,067 8 .2 % failed 1 1 .9 % failed

OR = 1.4 (1.1-1.8)

No sex differences

Bayley et al., JAGS, 2015;63:309

> High school > High school High school High school <High school <High school

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 Dementia during midlife is rare  Cognitive aging begins before midlife  Midlife cognitive complaints are common  But cognitive complaints are not confined to midlife (or to women)  Biomarkers in older adults with subjective memory complaints are not obviously different from biomarkers in

• lder adults without complaints or cognitive impairment.

 Memory complaints may be associated with objective cognitive loss, but often they are not.

Thus far…

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 History  Examination  Laboratory  Diagnosis/ contributing factors  Management

Approach to screening and treatment

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Follow-up as needed Refer for neurologist evaluation

Patient concerns?

No Yes

Informant concerns?

No Yes

• 1. History (patient and informant)
• Memory
• Function
• Medical and psychosocial
• Medications
• Family history

+

• 2. Examination
• Cognition
• Mood
• Physical / neurological

+/−

• 3. Laboratory

Clinician concerns for neuro-based impairment?

No Yes (Diagnosis) & Management

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Early-onset Alzheimer’s disease Frontotemporal dementia  Try to include an informant!  Memory  Function  Medical history / psychosocial history / drug history and current meds  Family history

History

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 General physical exam / neurological exam  Cognitive and behavioral observations  Cognitive screening  Mood screening

Mini-cog MMSE MoCA SLUMS AD8 IQCODE Beck GDS Hamilton Zung

Examination

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Laboratory

 General labs (metabolic panel, CBC)  Thyroid functions  B12?  Toxic (drug) screen  Brain imaging?

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 Awareness of normal cognitive aging  Depression or anxiety  Menopause as time of affective vulnerabilty  Sleep disturbance  Hot flashes (stress, sleep)  Family stressors  Adolescent children, empty nest, aging parents, marital discord  Career challenges  Medication side-effects  OTC sleep aids, prescription sedatives, anxiolytics, antidepressants, analgesics  Alcohol or substance abuse

Diagnosis / management

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Global Cognition Verbal Memory Executive Functions

• 1.00
• 0.80
• 0.60
• 0.40
• 0.20

0.20 0.40 0.60 0.80 1.00

+ 1 SD

• 1 SD

 RCT, 643 healthy postmenopausal women  Early group (<6 y) and Late group (≥10 y) after menopause  Mean duration 57 months  Estradiol 0.5 mg/d or placebo

ELITE (Early versus Late

Intervention Trial with Estradiol)

Henderson et al., Neurology 2016;87:699

What is the role of hormone therapy? Vascular health

Other management issues